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{"category": "Human Necessities", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
|
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Performing Operations; Transporting"}
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Is the categorization of this patent accurate?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.429688 | 0.025513 | 0.566406 | 0.046631 | 0.457031 | 0.148438 |
null |
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Human Necessities"}
|
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Chemistry; Metallurgy"}
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Is the patent correctly categorized?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.006897 | 0.002121 | 0.019165 | 0.014954 | 0.041504 | 0.013611 |
null |
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Human Necessities"}
|
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Textiles; Paper"}
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Does the category match the content of the patent?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.012817 | 0.001503 | 0.036865 | 0.001099 | 0.025513 | 0.001411 |
null |
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Human Necessities"}
|
{"category": "Fixed Constructions", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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Does the category match the content of the patent?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.012817 | 0.161133 | 0.036865 | 0.330078 | 0.025513 | 0.03418 |
null |
{"category": "Human Necessities", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
|
{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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Does the category match the content of the patent?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.660156 | 0.022949 | 0.59375 | 0.006104 | 0.597656 | 0.112793 |
null |
{"patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings .", "category": "Human Necessities"}
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{"category": "Physics", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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Is the category the most suitable category for the given patent?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.006683 | 0.142578 | 0.024414 | 0.043945 | 0.037842 | 0.605469 |
null |
{"category": "Human Necessities", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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{"category": "Electricity", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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Is the patent correctly categorized?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.416016 | 0.337891 | 0.449219 | 0.408203 | 0.613281 | 0.683594 |
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{"category": "Human Necessities", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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{"category": "General tagging of new or cross-sectional technology", "patent": "fig1 illustrates a victim who has signs of cardiac arrest and who is being treated by a rescuer c . the rescuer may be a person who is a bystander and who has taken a cpr course . the rescuer has applied the electrodes of an aed ( automatic external defibrillator ) 14 that was available at the site of possible cardiac arrest , and is performing chest compressions at the lower chest area 12 . the automatic defibrillator 14 can apply high - voltage ( e . g . 2 , 800 volts ) shocks when the intelligence built into the defibrillator confirms the presence of a rhythm that prompts delivery of an electrical shock . the defibrillator has a cable 16 with wires 20 , 22 having conductors that are connected to first and second electrodes 24 , 26 . the electrodes are attached to the skin of the victim at conventional locations under the right collar bone and left lower chest . the rescuer applies downward forces or compressions to the sternum . it is noted that in some cases a rescuer also may blow air into the mouth or nose of the patient by mouth - to - mouth or mouth - to - nose breathing , sometimes using a mask or barrier device . an electrically insulating sheet 32 has been placed between the rescuer and the patient , so the rescuer can continue to apply chest compressions when the defibrillator delivers an electrical shock . as an option , the rescuer may be prompted prior to the delivery of a shock by the aed , and the rescuer may choose to stop chest compressions for a few seconds ( generally less than 5 seconds ) to allow for the shock to be applied . current versions of aed &# 39 ; s require a \u201c quiet \u201d period of perhaps 12 to 25 seconds , when chest compressions are suspended and during which the intelligence of the defibrillator determines whether or not a shock is required . during this \u201c quiet \u201d period the computer intelligence applies algorithms to analyze the rhythm in the ecg signal to determine whether the patient has vf , in which case delivery of a shock is triggered . if the victim is producing a rhythm which would be indicative of a potentially beating heart ( perfusing rhythm ), no shock is delivered and continued cpr is advised . though current defibrillators may actually require only as little as 7 seconds to identify the presence of a non - shockable rhythm , chest compressions are stopped for a longer period . as mentioned above , such \u201c quiet \u201d periods substantially reduce the success of defibrillation and survival from cardiac arrest . multiple shocks may be required and therefore several \u201c quiet \u201d periods may occur during which cpr is suspended for periods of time that prejudice restoration of circulation . in accordance with the present invention , the application of chest compressions by the rescuer is not interrupted while the intelligence of the automated defibrillator determines whether a defibrillation shock is indicated . fig2 is a graph 40 showing one cycle of an ecg signal obtained from a patient with a healthy heart in perfusing rhythm . the electrical cycle is conventionally identified by the letters characteristic of the beating heart , which are a pqrst complex . the five letters indicate five points along the electrical cycle . the main area of interest is the area qrs , in which there is an electrical \u201c spike \u201d. this spike is the part of the ecg cycle which corresponds to the electrical event which triggers the mechanical pumping of the ventricles and which creates the heartbeat and blood flow to the body . fig3 is a graph showing a typical ecg of a heart in vf . the qrs complex is not present , which indicates a quivering heart , which is a heart with vf and which does not produce blood flow and perfusion of the vital organs . the p - q and s - t parts of the electrical cycle are also absent . fig4 illustrates an ecg from a patient with a healthy heart generating perfusing rhythms , but in the presence of artifacts due to chest compressions . the graph 60 includes compression artifacts 62 resulting from chest compressions , together with qrs complexes 64 , labeled 64 a - 64 d and resulting from the electrical signals of the beating heart . the electrical signal of a healthy heart is typically more regular in the shape of the signal in each cycle and in the time periods of the cycles . in fig4 , the chest compression artifacts 62 are also applied regularly although their amplitude varies somewhat . the frequency of the - beating heart qrs complexes 64 and the frequency of the chest compressions and corresponding compression artifacts 62 are close , but are never exactly the same . as a result , there is a constant phase shift between the qrs complexes 64 and the compression artifacts 62 . the fact that there is a constant change in phase between the compression artifacts 62 in fig4 and the qrs complexes 64 , and the fact that the compression artifacts 62 are of brief duration and high amplitude , allows some of the qrs complexes to be separated out for analysis . in one approach , the ecg signal is modified by deleting all pulses of high amplitude , including the peaks of the large amplitude pulses and perhaps 12 . 5 % of the period on either side of each large pulse peak . large amplitude peaks may be defined as those of an amplitude exceeding a certain multiple of the average amplitude and having a large derivative ( slope ), but other criteria can be used . the resulting graph then can be analyzed in a manner similar to analysis of ecg signals which are not corrupted by chest compression artifacts . in another approach , qrs complexes 64 of fig4 lying about halfway between adjacent compression artifacts , such as 64 a , 64 b , 64 c , and 64 d , are taken and analyzed . perhaps four or five of the qrs complexes that lie about halfway between compression complexes ( e . g . between 25 % and 75 % of the time distance between compression artifacts 62 ) can be added together where points such as the q &# 39 ; s ( point of high slope and high slope change , lying in between the artifacts 62 ) overlap . a single qrs complex such as 64 b is cross - correlated with the average of the four or five qrs complexes . in fig4 , the time c between the peak signals 66 of the chest compression artifacts are regular , and the periods a 1 extending 12 . 5 % before and after each compression artifact peak 66 are excluded from analysis . only the periods b 1 extending from 25 % to 75 % of the peak compression artifacts are analyzed for the presence of qrs complexes . in fig4 , three qrs complexes 64 a , 64 b , 64 c lie completely within the periods b 1 , fig5 shows an ecg signal 70 from a patient whose heart is undergoing vf while chest compressions are being applied . the chest compression artifacts 82 can be removed by one of the processes described above . that is , the only periods analyzed are the periods b 2 that extends 12 . 5 % before and after each artifact 82 . the ecg signal in periods b 2 do not display any qrs complexes . that is , in the graph there are no sharp spikes between the compression artifacts , which indicates the presence of the bizarre vf condition characterized by the absence of qrs . this triggers delivery of a defibrillating shock . a large number ( e . g . 60 consecutive b 2 periods ) of signals in periods b 2 are analyzed to try to detect qrs complexes , to be sure that all qrs complexes do not happen to lie in the periods a 2 of chest compressions . the periods b 1 and b 2 in fig4 and 5 are analyzed to determine whether or not a group of ecg signals of periods b 1 or b 2 are of the same shape and / or have the shape of a qrs complex . one way is take the signals portions of durations b 1 at 64 a , 64 b , 64 c in fig4 and compare them . when comparing signals of duration b 1 at 64 a - 64 c , the absolute value of each signal is taken . the absolute value is autocorrelated to emphasize large amplitude change such as near the points q . then , pairs of signal portions of durations b 1 at 64 a - 64 c are cross - correlated . this involves multiplying corresponding points along the two signals to obtain a cross - correlation signal followed by determining the area under the cross - correlation signal . after the area is obtained , only one signal is shifted slightly and a new cross - correlation signal is obtained . this is repeated until the cross - correlation signal whose area is greatest is obtained . such cross - correlation numbers are obtained for a plurality of pairs of signals . in fig4 , pairs of signals 64 a , 64 b , or 64 c , 64 d are similar , so the sum of the cross - correlation numbers ( areas under the best cross - correlation graphs ) is high , indicating that all signals ( of periods b 1 ) are similar . in fig5 , the cross - correlation numbers are low , indicating that all signals ( of periods b 2 ) are not similar . fig7 - 14 contain graphs indicating how signals representing vf and qrs in the presence of chest compression artifacts are analyzed by an algorithm that uses crosscorrelation and autocorrelation . fig7 - 10 are all for a ecg signal for a case of vf , while fig1 - 14 are all for an ecg signal for a case of qrs complexes . fig7 contains a graph 100 that is a raw ecg signal for a patient with vf , in the presence of chest compression of about the same amplitude as peaks of the vf alone . fig8 is a graph 102 that represents the wavelet transform of fig7 . the wavelet transform is largely similar to the derivative , in that the slopes , but not absolute values , of the signals of fig7 are present in fig8 . the wavelet transform is also similar to taking the dc ( direct current ) component out of the ac ( alternating current ) signal of fig7 . fig9 is a set 104 of graphs obtained by first taking spike regions for the seven largest peaks ( e . g . s 1 through s 7 ) in fig8 . each spike region includes a peak and the signal extending 0 . 2 second prior to and 0 . 2 second after the peak . the peaks of the spike regions are aligned along the horizontal axis so they all lie on a vertical line 110 of fig9 . fig1 is a set 112 of graphs obtained by computing the autocorrelation of the seven spike regions of fig9 to obtain dark and thick line 114 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 121 - 127 . the empty \u201c white \u201d space between the thick line 114 and each of the thin lines 121 - 127 is calculated . if there is a large white area , this indicates vf for that thin line . if there is a small white area , this indicates a qrs complex for that thin line . the \u201c white \u201d space for a thin line is the integral of the magnitude ( absolute value ) of the difference between line 114 and one of the thin lines 121 - 127 . fig1 contains a graph 130 that is a raw ecg signal containing qrs complexes . fig1 is a graph 132 that is a wavelet transform of fig1 . fig1 includes a set 134 of graphs obtained by following the same process described for fig9 . that is , applicant first takes spike regions for the seven largest peaks s 11 - s 17 in fig1 . each spike region includes a peak and the signal portion 0 . 2 second prior to and following the peak . fig1 is a set 142 of graphs obtained by computing the autocorrelation of the seven spike regions of fig1 to obtain dark and thick line 144 , and by computing the crosscorrelations of the seven spike areas to obtain the thin lines 151 - 157 . the empty \u201c white \u201d space between the thick line 144 and each of the thin lines 151 - 157 is calculated , as the integral of the magnitude of the difference between the thick line and each thin line . if a small white area ( an integral smaller than a preset amount ) has been calculated for a thin line , this indicates a qrs complex , while a large white area ( an integral larger than the preset amount ) indicates vf for that thin line . a visual comparison of the crosscorrelations of fig1 and 14 shows that for the vf set 112 of fig1 the thin lines 121 - 127 are largely out of phase with the thick line , which results in a large \u201c white \u201d area indicating vf . for the qrs complexes of fig1 , the thin lines 151 - 157 are largely in phase with the thick line , especially near the center 110 of the thick line ; this indicates a qrs complex . actual computing of the \u201c white \u201d area between a thick and thin line in fig1 and 14 will show this difference . in applicant &# 39 ; s algorithm , if a majority ( four of the seven ) spike regions have less than the predetermined white area ( between themselves and the thick line ), then the ecg is deemed to be a genuine qrs rhythm ( corrupted by compression artifacts ). if a majority ( four of seven ) spike regions have more than the predetermined white area then the ecg is deemed to represent vf . the white area which is the dividing line can be determined by tests on patients in emergency facilities . another approach is to look for large changes in signal amplitude over short periods of time . in fig4 , the average of maximum changes in each cycle is a change f of about 10 mv during a compression artifact . in fig6 , which represents ecg signal portion b 1 at 64 a of fig4 , the signal between points q and r has a voltage that rapidly increases . the increase is from \u2212 3 . 2 mv to + 1 . 8 mv during a period e of about 0 . 05 second for a slope ( derivative ) of + 100 mv / sec . this is followed by a voltage decrease from r to s of 1 . 8 mv during a period of about 0 . 03 second for a slope of \u2212 60 mv / sec . a slope of at least on the order of magnitude of 30 mv / sec ( absolute value ) between points differing in amplitude by at least about 10 % of the changes in amplitude at the compression artifacts , indicates a portion of a qrs complex . the presence of two successive opposite slopes of the above magnitude is a much stronger indication of a qrs complex . in fig6 , each change from q to r and from r to s is more than 10 % of the change f ( fig4 ) in the compression artifact . this indicates a qrs complex . in the periods b 2 of fig5 there are no changes of more than 10 % of the change g produced by the compression artifact . the detection of qrs complexes can be confirmed by the fact that a detection of a signal portion that is part of a qrs complex , should constantly change phase with respect to the chest compression artifact in each cycle ( which is the period between the middles , or peaks of two successive chest compression artifacts ). thus , the qrs complex will regularly occur almost simultaneously with the chest compression artifacts when the qrs complex cannot be detected , then qrs complexes will occur between artifacts and can be detected , and so forth . it is possible to set the frequency of chest compressions so they are close to expected heart beat cycles so a series of successive qrs complexes can be detected between chest compression . it is possible to analyze the ecg signals 60 , 70 ( fig4 and 5 ) in regions that include periods a 1 , b 1 that contain the chest compression artifacts 62 , 82 . however , it can be difficult to make such an analysis due to the high amplitude of the artifacts . one way is to obtain the profile of very regular chest compression artifacts ( especially when a chest compressing machine is used ) and cancel them in the ecg signal with signals that are 180 \u00b0 out of phase . thus , the invention provides a method for operating an aed ( automatic external defibrillator ) by a rescuer who can provide chest compressions , without the need for a extended interruption to provide \u201c clean \u201d ecg signals for detecting the heart rhythm and determining the need for an electrical shock . a possible exception is a hiatus that is a short period of time of a few seconds ( perhaps 3 seconds but no more than 5 seconds ) if the rescuer is not isolated from the patient &# 39 ; s chest by an insulating sheet or is applying mouth - to - mouth resuscitation . the ecg signal which includes chest compression artifacts , is analyzed to determine the presence of a perfusing rhythm or of vf , in the presence of the compression artifacts . the analysis can continue without interruption ( except possibly when a defibrillation pulse is applied ). compression artifacts are not removed but rather the qrs presence is identified in spite of the contamination of the signal by artifacts caused by chest compression . the method can include analyzing ecg signal portions lying between successive compression artifacts . in that method , applicant relies upon the constant phase shift between chest compressions and any heart beats , to provide qrs complexes that lie about halfway ( e . g . between 25 % and 75 % of the time period between successive artifacts ) between successive compression artifacts in about half of the cycles . these halfway signal portions can be isolated and analyzed apart from the rest of the ecg signal . the method can include analyzing the corrupted ecg signal by producing a transform such as a wavelet transform . then a group of spike regions thereof are selected that include high amplitude peaks and signals immediately adjacent to each peak . the autocorrelation of the group of spike regions is compared to crosscorrelations of the group of spike regions . signals representing \u201c white \u201d areas between the autocorrelation and each crosscorrelation are produced to determine whether the ecg signal represents qrs complexes or a vf condition . in practice , two or more methods can be applied to analyze the ecg signal and they can all be used to judge whether or not a defibrillating shock should be applied . the novel features of the invention are set forth with particularity in the appended claims . the invention will be best understood from the following description when read in conjunction with the accompanying drawings ."}
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Does the patent belong in this category?
| 0.25 |
a941ef733ce8bd22de34188f77b5ce32ec5e5f6d9f18dde5a95e00517997e435
| 0.777344 | 0.472656 | 0.75 | 0.71875 | 0.789063 | 0.558594 |
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{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Physics"}
|
{"category": "Human Necessities", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
|
Does the patent belong in this category?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.026001 | 0.248047 | 0.091309 | 0.166992 | 0.175781 | 0.245117 |
null |
{"category": "Physics", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
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{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Performing Operations; Transporting"}
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Does the category match the content of the patent?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.208984 | 0.007355 | 0.292969 | 0.014954 | 0.398438 | 0.112793 |
null |
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Physics"}
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{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Chemistry; Metallurgy"}
|
Is the categorization of this patent accurate?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.080566 | 0.011353 | 0.074707 | 0.129883 | 0.146484 | 0.170898 |
null |
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Physics"}
|
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Textiles; Paper"}
|
Is the patent correctly categorized?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.03418 | 0.003601 | 0.081543 | 0.003372 | 0.066406 | 0.007568 |
null |
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Physics"}
|
{"category": "Fixed Constructions", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
|
Is the patent correctly categorized?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.03418 | 0.039551 | 0.081543 | 0.141602 | 0.06543 | 0.376953 |
null |
{"category": "Physics", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
|
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting"}
|
Is the category the most suitable category for the given patent?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.054199 | 0.000179 | 0.027222 | 0.000368 | 0.246094 | 0.005371 |
null |
{"category": "Physics", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
|
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Electricity"}
|
Is the patent correctly categorized?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.194336 | 0.003082 | 0.275391 | 0.002396 | 0.574219 | 0.002396 |
null |
{"patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein .", "category": "Physics"}
|
{"category": "General tagging of new or cross-sectional technology", "patent": "according to the present invention , the four steps of ( a ) timely fixation for the purposes of cell preservation , ( b ) producing a cross - linked matrix in the plasma layer ; ( c ) decreasing surface tension and retarding evaporation at the fresh blood spread by by immersion in a non - polar ( water immiscible ) solvent , and ( d ) performing a chemical reaction by diffusing reagents across an interface , are combined for the purpose of stabilizing both the cell shape and the smoothness and homogeneity of the plasma layer . distortion of the plasma layer during drying of cell monolayers is solved by producing the cross - linked matrix before drying . an agent for subsequent cross - linking in the plasma is dissolved in the plasma while the blood is still a liquid suspension . the activating or polymerizing agent is dissolved in the non - polar solvent . concentrations are adjusted so that cross - linking occurs within about the first minute of immersion of the wet blood spread on the slide in the non - polar solvent while excessive reactions are prevented . by proper adjustment of conditions of agent to be cross - linked , polymerizing agent , blood spreading process , non - polar solvent and time , one may separate two phenomena of distortion . first , by using a polymerizing agent which acts chiefly on the plasma component , migration of plasma during the subsequent drying is eliminated . in this case , the cells are left unaffected , except that surface tension forces as they would act on the cells are greatly reduced . the spreading or stretching of the cells after this treatment is intermediate between fixed cells and those without the treatment . by using a polymerizing agent that also fixes the cells before they are dry , one may preserve both a smooth , undistorted plasma layer and cells without distortion . these cells generally have the appearance , after drying , of cells usually seen only in wet preparations . loss of central palor in red blood cells as described in u . s . pat . no . 4 , 209 , 548 does not happen under these conditions . any suitable cross - linking agent may be used in the process of the present invention . typical cross - linking agents include formaldehyde , glutaraldehyde and trichloroacetic acid . cross - linking action may be by structural change in the agent to be cross - linked , as with trichloroacetic acid , or by formation of additional covalent bonds , as with an aldehyde . while any suitable agent with these properties may be used , the agent of choice is glutaraldehyde . properties of the agent to be cross - linked include large molecular weight , solubility in the plasma of human blood , non - reactivity with either the plasma or particulate components of human blood , but responding to the cross - linking agent , and not causing cell aggregation or attachment of blood components to the cell surface . optimum results were obtained by using human serum albumin as agent to be cross - linked and glutaraldehyde as a cross - linking agent . any suitable non - polar solvent may be used in the present invention . properties of such a solvent include low surface tension , non - miscible with water but capable of dissolving the cross - linking agent , and non reactive with water , blood or the reagents used in cross - linking . the optimum solvent used with glutaraldehyde and human serum albumin is cyclohexane . any suitable blood spreading process , such as the spinner process , the coverslip process and the wedge process , may be used in this invention , although it is preferred to employ the spinner process because a larger usable monolayer area is produced . the following examples further define the present invention . it should be noted , however , that these examples are intended to illustrate , and in no way are intended to limit the invention . the agent , used herein , for subsequent cross - linking is human serum albumin , the coloring agent is a dye fast green sf ( color index # 42053 ), the slide preparation is by a spinner process described in u . s . pat . no . 3 , 827 , 805 , the non - polar solvent is cyclohexane and the cross linking or activating agent dissolved in cyclohexane is glutaraldehyde . human serum albumin ( hsa ) is a 30 % aqueous solution . glutaraldehyde solution is 1 / 6 of the maximum or saturation concentration in cyclohexane . it is prepared by shaking together a 25 % aqueous glutaraldehyde solution and the pure cyclohexane at room temperature . subsequently , the saturated solution is diluted with pure cyclohexane in ratio of about 1 part in 6 . two parts of blood are mixed with one part of human serum albumin solution . a monolayer spread is made on the slide using a spinner and is immediately immersed in cyclohexane glutaraldehyde . after 30 seconds , the slide is transferred to pure ( clean ) cyclohexane where the unreacted glutaraldehyde is rinsed away . upon removal of the slide from the clean cyclohexane bath , the solvent is permitted to evaporate and the slide is dried . both plasma and cells are preserved , free of distortion from their original shape . example i is repeated using trichloracetic as the cross - linking agent for the human serum albumin . immersion of the wet blood film is kept down to about 15 seconds in cyclohexane containing about 1 / 100 % of trichloroacetic acid . the cross - linking agents , as in example i , above , acts by crossing the boundary between the non - polar solvent and the water wet monolayer of blood , and by performing its cross - linking chemical reaction after further diffusion on the water side of the boundary . among other reactions the trichloroacetic acid causes denaturation of the albumin which then precipitates in place to the extent that a smooth plasma layer is obtained . in this example , only plasma is preserved free of distortion . since trichloroacetic acid does not fix the cells , they are subjected to stretching forces during drying . as a result they resemble cells as they would appear in conventional monolayer blood spreads . while specific components of the present system are defined in the examples above , many other variables may be introduced which may in any way affect , enhance or otherwise improve the invention . these are intended to be included herein . while variations are given in the present application , many modifications and variations will occur to those skilled in the art upon reading the present disclosure . these , too , are intended to be included herein ."}
|
Is the patent correctly categorized?
| 0.25 |
b37c5c6eb010c56c226418769d76a416e3e69238000d5d2023fb63d69b1a10c8
| 0.03418 | 0.267578 | 0.081543 | 0.339844 | 0.06543 | 0.462891 |
null |
{"category": "Performing Operations; Transporting", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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{"category": "Human Necessities", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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Does the category match the content of the patent?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.71875 | 0.490234 | 0.710938 | 0.425781 | 0.820313 | 0.757813 |
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Performing Operations; Transporting"}
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{"category": "Chemistry; Metallurgy", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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Is the patent correctly categorized?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.014954 | 0.007355 | 0.091309 | 0.006287 | 0.289063 | 0.018555 |
null |
{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Performing Operations; Transporting"}
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Textiles; Paper"}
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Does the patent belong in this category?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.095215 | 0.000444 | 0.172852 | 0.001457 | 0.439453 | 0.003937 |
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{"category": "Performing Operations; Transporting", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Fixed Constructions"}
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Does the category match the content of the patent?
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b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.71875 | 0.142578 | 0.710938 | 0.162109 | 0.820313 | 0.412109 |
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Performing Operations; Transporting"}
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting"}
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Is the categorization of this patent accurate?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.021606 | 0.005219 | 0.114258 | 0.029785 | 0.359375 | 0.139648 |
null |
{"category": "Performing Operations; Transporting", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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{"category": "Physics", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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Is the categorization of this patent accurate?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.621094 | 0.050293 | 0.578125 | 0.031738 | 0.683594 | 0.106934 |
null |
{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "Performing Operations; Transporting"}
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{"category": "Electricity", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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Is the categorization of this patent accurate?
| 0.25 |
b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.021606 | 0.09668 | 0.114258 | 0.230469 | 0.359375 | 0.242188 |
null |
{"category": "Performing Operations; Transporting", "patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims ."}
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{"patent": "referring now in detail to the drawings , more specifically fig1 the reference numeral 20 denotes generally a vehicular automatic occupant sensing anti - carjacking system constructed in accordance and embodying theinvention . the automatic occupant sensing anti - carjacking system 20 contains an electronic command control unit 7 , mounted in a hidden location within a motor vehicle 64 , in fig5 . the command control unit 7 is configured for communication with an array of sensors 21 . as will be observed from fig1 the command control unit 7 is operatively connected to a combination keypad - monitor 6 for user programming includingbypass and override functions . such programming may include a selection of available options such as , sensor selections , audible warning devices , timers , light flashers etc . an array of sensors 21 are operatively connected to a command control unit 7 . the sensors may include pressure sensors , infra red sensors , motion detectors , ignition sensors , shift lever position sensor , rpm sensors etc . these are all conventional sensorswhich are used in conjunction with other existing vehicular protection systems and are well known in the market . selected system carjacking responses are actuated by signal from the command control unit 7 to an array of interfaced relays 22 . the relays 22 are strategically positioned at various locations throughout the vehicle 64 and with each adapted to serve a dedicated function . among the relays 22 are an ignition disable relay 10 , starter disable relay 11 , fuel disable relay 12 , audible device relay 14 , lighting relay 13 . internal and external audible devices 19 are operatively connected to the audible device relay 14 within the vehicle 64 for the purposes of providing internal audible functions to drive the carjacker out of the vehicle 64 , as well as , external audible functions to provide an audible alert to draw attention to the vehicle 64 and the carjacker . the combination keypad - monitor 6 may be employed to program the command control unit 7 to recognize only certain of the sensors 21 and which of the relays 22 will be actuated under specific circumstances and in which sequence the relays 22 will be activated . for example , the authorized occupant can program the operator &# 39 ; s seat pressure sensor 61 , referring to fig5 this sensor 61 employs a low cost versatile pressure transducer 43which will allow the authorized occupant to program a specific voltage signal to the command control unit 7 . any of the pressure actuated sensors1 may be variable , sensor 61 was chosen for simplicity . the voltage signal will be relative to the amount of pressure that the authorized occupant exerts on the sensor 61 while sitting in the authorized occupant &# 39 ; s seat 56 . this will allow an authorized operator to program a specific voltage signal from sensor 61 in the memory of the command control unit 7 allowingonly an authorized occupant to operate the vehicle 64 within the parametersstored in the memory of the command control unit 7 . the keypad - monitor 6 may also provide on screen verification of all programming activities through its liquid crystal diode monitor and keypad . additionally , the keypad - monitor 6 may be employed to program the command control unit 7 to appropriately adjust sensitivity of sensors 21 , as well as , appropriately actuating the relays 22 . the automatic occupant sensing anti - carjacking system 20 includes an ignition sensor 2 which determines when ignition is on as an additional input to command control unit 7 . ignition sensor 2 is preferably a wire connected to the vehicle 64 &# 39 ; s ignition circuit ( not shown ) for producing avoltage signal when the ignition is on and no voltage signal when the ignition is off . the automatic occupant sensing anti - carjacking system 20 also includes an engine rpm or revolutions per minute sensor 3 which determines when the engine is running as an additional input to the command control unit 7 . rpm sensor 3 is preferably a wire connected to thevehicle 64 &# 39 ; s ignition circuit ( not shown ) for providing a voltage signal when the engine is running and for providing no voltage signal when the engine is not running . the automatic occupant sensing anti - carjacking system 20 also includes an shift lever position sensor 4 which determines what position the vehicle 64 &# 39 ; s shift lever ( not shown ) is in as an additional input to the command control unit 7 . shift lever position sensor 4 is preferably a wire connected to the vehicle 64 &# 39 ; s neutral safety switch ( not shown ) for providing a voltage signal when the shift lever ( not shown ) is in the reverse or any forward drive selection e . g . first , second , third and overdrive on equipped automatic transmissions and for providing no voltagewhen the shift lever is in the neutral or park position . in vehicle 64 &# 39 ; s with manual transmissions a clutch pedal sensor ( not shown ) is used to signal the command control unit 7 of vehicle 64 movement . however , other sensing devices for determining whether the vehicle 64 is in neutral , drive , or reverse or whether the vehicle 64 is moving or not moving would be realized by one having ordinary skill in the art as providing the same purpose . auxiliary sensors 5 such as , motion sensors , infra red sensors , and pressure sensors may also be used . the automatic occupant sensing anti - carjacking system also includes pressure sensors 1 used to determine if a seat or other monitored area inside vehicle 64 is occupied or unoccupied as an additional input to the command control unit 7 . thus this is what is referred to as the occupant sensing aspect of the present invention . these sensors 1 which are pressure sensitive and are strategically located in the interior seating and floor area of the vehicle 64 . referring to fig5 which is a top viewof a block diagram of vehicle 64 shows one of many possible , strategic installations of pressure sensors . the reference numerals 51 , 55 , 62 and 63 denote fixed signal pressure sensors which detect pressure on the floorarea of the vehicle 64 . sensor 51 is located in the floor of the rear cargoor trunk area . sensor 55 is located in the floor area of the rear seats . sensors 62 and 63 are located in the floor area of the front seats . the reference numeral 52 denotes the rear seat of vehicle 64 . the reference numeral 53 denotes a fixed signal pressure sensor located in the backrest cushion of the rear seat 52 of vehicle 64 . the reference numeral 54 denotes a fixed signal pressure sensor located in the seat cushion of the rear seat 52 of vehicle 64 . the reference numeral 56 denotes the front seat of vehicle 64 . the reference numerals 57 and 58 denote fixed signal pressure sensors located in the backrest cushion of the front seat 56 of vehicle 64 . the reference numerals 59 and 60 denote fixed signal pressure sensors located in the passenger side of the seat cushion of the front seat 56 of vehicle 64 . the reference numeral 61 denotes the authorized operator variable signal pressure sensor , referring to fig5 located in the seat cushion of the operator &# 39 ; s seat 56 of the vehicle 64 . this sensor 61 responds to the seat pressure that the operator exerts on the operator &# 39 ; s seat . the advantage here is that is unlikely that different operators will have the same voltage signal identification . this allows the command control 7 to identify the authorized occupant by monitoring the output signal 45 of the pressure sensor module 48 . the command controlunit 7 continuously monitors the vehicle 64 sensors 21 automatically . the pressure transducer 43 can be easily modified to fit almost any application including the present invention . referring to fig4 the pressure sensor 42 comprises a low cost capacitive type versatile pressuretransducer 43 which is an electrical pressure transducer which is operatively connected to a pressure sensing pad 44 or other sensing apparatus to transmit the pressure signal to the pressure transducer 43 via rubber or plastic tubing . the pressure transducer contains a sensor module 48 providing an output signal 45 indicative of fluid pressure effective thereon to the command control unit 7 which also sends an input signal 46 to the pressure sensor 42 pressure transducer 43 as well as a ground connection at 47 . the flexible plastic or rubber sensing pad 44 andplastic or rubber tubing are readily available on the market . a well known manufacturer and supplier of such products is b . f . goodrich of akron , ohio . although a specific manufacturer and materials for the flexible liquid filled sensing pad 44 have been disclosed there are other well known manufacturers and materials which may be used . a liquid filled pressure sensing pad 44 is operatively connected to a pressure transducer 43 . although fig4 shows the components separately the pressure transducer and pressure sensing pad may be an integral unit . the command control unit 7 is operatively connected to the pressure transducer 43 . thepressure sensing pad 44 contains a liquid that has the properties of any well known ethylene glycol based solution . one such solution is peak antifreeze and coolant manufactured by old world industries inc ., northbrook , ill . although a specific solution has been disclosed it is well understood that numerous other liquid solutions may be used as well . the pressure transducer 43 accordingly reacts quickly to changes in the amount of pressure applied to the pressure sensing pad 44 as the authorized operator or occupant occupies a pressure sensor 42 monitored seat in the vehicle 64 . when a seat is occupied the liquid pressure sensing pad 44 senses the pressure of the occupant as they occupy the seatsurface ( not shown ) this results in a change in pressure of the liquid inside the pressure sensing pad 44 . this change in pressure is received bythe pressure transducer 43 which transmits an output signal 45 of the sensor 42 which is monitored by the command control unit 7 . the output signal 45 is analyzed as a report of an occupied seat . the sensor 42 monitors the input pressure signal 49 while the seat is occupied . these input pressure signals 49 are analyzed and compared with those stored in the memory of the command control unit 7 . the output signal 45 of the sensor 42 therefore will vary depending on the input pressure signal 49 which is relative to how much pressure is applied to the pressure sensing pad 44 . when the seat is vacated the pressure transducer furnishes a constant output signal 45 for example a 0 - value . this output signal 45 is recognized by the command control unit 7 as an unoccupied seat . intentional or unintentional movements of the seated occupant ( s ) on the pressure sensing pad 44 are recognized by the command control unit 7 and would not interfere with the normal system operation . a transducer performing this function is the model number p155 manufactured by kavlico corporation , moorpark , calif . although a specific pressure transducer has been disclosed , it is well understood that numerous other pressure transducers can be used to convert the input pressure signal 49 into an output electrical signal 45 to the command control unit 7 . a pressure switch ( not shown ) may be used to turn on the command control unit 7 when the ignition is not on . this prevents unecessary voltage drainon the system battery 8 and the vehicle battery 9 . thus , when the ignition is not on the pressure activated switch ( not shown ) will provide battery power to the command control unit 7 when any monitored seat in the vehicleis occupied . the pressure switch ( not shown ) may be seperate or incorporated into the pressure sensor 42 . the output signal 45 of the authorized occupant is stored in the memory of the command control unit 7 and is constantly compared with the output signal 45 of the pressure sensor 42 . any unprogrammed or unauthorized signals will activate the disablement sequence at 33 in fig3 . this sensor 42 allows an authorized occupant to easily operate the system 20 while making it virtually impossible for an unauthorized occupant to operate the vehicle 64 . the authorized occupant can , after programming thecommand control unit 7 operate the vehicle 64 without the need for transmitters , buttons or switches or other manual devices to operate its carjacking functions . the command control unit 7 receives inputs from ignition sensor 2 , pressuresensors 1 , shift lever position sensor 4 , engine rpm sensor 3 and auxiliarysensors 5 , as well as , a determination of a connection to vehicle 64 battery 9 and command control unit 7 battery 8 . the command control unit processes these inputs and if necessary , controls system 20 devices , 15 , 16 , 17 , 18 , 19 by controlling corresponding relays 10 , 11 12 , 13 and 14 located in strategic locations in vehicle 64 . command control unit 7 circuitry includes any suitable microprocessor , for example , an intel microcontroller chip such as , 8031 or 8096 , or a motorola microcontroller chip such as a 68332 together with appropriate memory and interfacing . relays 22 are normally open and their operation are described below in conjunction with the operational flow charts shown in fig2 and 3 . otherwell - known signal conditioning circuitry can be used between command control unit 7 and the system devices 23 , including but not limited to , power resistors , as well as appropriate isolation circuitry such as capacitive filters etc . command control unit 7 is designed to operate the automatic occupant sensing anti - carjacking system 20 as shown by the flow chart of fig2 to provide automatically operated anti - carjacking protection . to a vehicle 64operator desiring automatically operable anti - carjacking protection in any carjacking scenario . this system offers anti - carjacking protection regardless whether the authorized occupant is inside or outside of the vehicle 64 , regardless whether the ignition is on or off in vehicle 64 , regardless whether the engine is running or not running in the vehicle 64 , regardless whether the vehicle 64 is attended or unattended , regardless whether the carjacker attempts to take the authorized occupant hostage andforce the authorized occupant to drive the vehicle 64 , regardless whether the carjacker attempts to take the authorized occupant hostage by forcing the authorized occupant into the trunk of the vehicle 64 and other likely scenarios . other than the programming of the command control unit 7 there are no manually operated buttons or switches needed to activate carjacking protection functions . the authorized occupant need not be concerned with turning it on or off as it works automatically requiring no further authorized occupant activation . appropriate indicators such as a chirp speaker or led indicators may be used to indicate system 20 status to the authorized occupant . the command control unit 7 retrieves the stored input , at 25 in fig2 from the array of sensors 21 . the command control unit 7 then begins to compare all signal inputs , at 30 in fig2 with those stored in the memory of the command control unit 7 . if any signals are not within programmed parameters the command control unit 7 activates the anti - carjacking disabling sequence at 33 in fig3 automatically . during the disablement sequence the command control continues to check sensor inputs at 34 , the hazard lights 18 at fig1 flash continuously for a pre - determined amount of time at 35 in fig3 before engine disablement at 36 , 37 and 38 to allow the operator time to safely drive the car out of traffic prior to engine disablement , at 36 , 37 and 38 , by the command control unit 7 . at the expiration of this pre - determined time the hazard lights 18 will continue to flash and the audible devices 19 , infig1 will begin to sound at 39 after disablement at 36 , 37 and 38 . audible devices included for use in the anti - carjacking disablement sequence are interior and exterior audible devices 19 . there are numerous types of well known sirens , speakers , and horns which may be used for thispurpose . the command control unit 7 includes a timing device for controlling both audible devices 19 and hazard flashers 18 so that they operate for a maximum time period and then automatically shut off . unless enabled by an authorized operator the engine will remain disabled at 36 , 37 and 38 and the hazard flasher 18 and audible devices 19 , referring to fig1 will stop after 15 minutes or other pre - determined amount of time . the system 20 will continue to monitor sensors 21 at 40 and continue disabling at 41 until the appropriate input parameters are received by thecommand control unit 7 . if there are no input signals the command control unit 7 will automatically disable vehicle 64 at 27 in fig2 . for increased anti - carjacking protections the command control unit 7 checksfor disablement status at 29 , in fig2 the engine can only be enabled , at28 , once disabled , at 36 , 37 and 38 in fig3 by an authorized occupant sitting and occupying the operator &# 39 ; s seat 56 , in fig5 of the vehicle 64where pressure sensor 61 will send a signal to the command control unit 7 that there is an authorized occupant in the vehicle 64 . the command control unit 7 will then enable the vehicle &# 39 ; s 64 engines at 29 in fig2 and deactivate hazard lights 18 and deactivate audible devices at 19 and return the system 20 to monitor mode at 24 . the vehicle 64 can also be enabled by an authorized operator using the reset and override functions of the monitor - keypad 6 . a carjacker would not be able to prevent disablement at 36 , 37 and 38 as the array of sensors 21 would signal the command control unit 7 of an unauthorized occupancy . the command control unit 7 monitors the system 20 at 24 , it then retrieves the signal at 25 , identifies the signal at 26 , checks the parameters of the signals at 30 and since the carjackers signal would be identified as unauthorized at 31 the command control unit 7 would activate the disabling sequence at 32 . another method the thief may attempt is to disconnect the vehicle 64 battery 9 and the system 20 battery 8 in an attempt to enable the system 20 . since all relays 22 in the system 20 are normally open and must be energized by the command control unit 7 disconnection of the batteries at 8 and 9 will only serve to put the system 20 in the disablement mode at 27in fig2 . it is important that the anti - carjacking prevention features be automatically initiated , prior art devices which utilize remote transmitters and hidden switches are not reliable as the carjacker may force coerce the operator to give up the transmitter , the operator may forget to carry the transmitter , the operator may be coerced prior to entering or shortly after exiting their vehicles the operator may be injured by the carjacker and be unable to use the transmitter or activate any hidden switches . also prior art devices using remote transmitters onlyprotect the vehicle from carjacking while the engine is running and the operator is in the vehicle . they offer no protection if the operator failsto activate the transmitter , forgets the transmitter , the vehicle exceeds transmitter signal range prior to the operation of the transmitter signal or the carjacker obtains the transmitter . the present invention as herein described makes it virtually impossible foran carjacker to obtain the vehicle 64 during an attempted carjacking in anyscenario . to illustrate the capabilities of the present invention , several scenarios are described below which demonstrates the unequalled protection afforded by the automatic occupant sensing anti - carjacking system 20 of the presentinvention : assume the operator drives vehicle 64 to the grocery market and turns the engine off and leaves the vehicle unoccupied . the array of sensors 21 willsend signals to the command control unit 7 that the vehicle 64 is unoccupied . the command control unit will then automatically initiate ignition , fuel and starter disablement at 27 in fig2 until enabled by an authorized occupant . the authorized operator returns to vehicle 64 and occupies the operator &# 39 ; s seat 56 the array of sensors 21 will send a signalto the command control unit 7 that an authorized occupant is in the vehicle64 and the command control unit 7 will automatically enable at 28 the vehicle 64 systems 23 . additionally , if an unauthorized operator enters the unoccupied vehicle 64 the array of sensors 21 will send signals to thecommand control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . in another scenario , the authorized operator is stopped waiting for a traffic light to change when a carjacker appearing at the window points a gun at the authorized operator and demanding the vehicle 64 . to end this scenario and the possibility of injury , the authorized operator merely complies with the carjacker &# 39 ; s demands knowing that the vehicle 64 will not get more than a pre - determined amount of time away , for example 60 seconds . the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that an unauthorized operator has entered vehicle 64 . the command control unit 7 will than automatically initiate the anti - carjacking disablement sequence at 33 in fig3 . additionally , the vehicle 64 hazard lights 18 will flash continuously , at 35 notifying the authorized operator that the anti - carjacking disablement sequence has begun and the carjacking attempt will be foiled . at a pre - determined time after the hazard lights 18 began flashing , at 35 , for example , 60 seconds later the carjacker will then decide to abandon the carjacking , compelled by the painful sound of the interior audible device at 39 in fig3 . it is likely that the carjacker will be observed as vehicle 64 is abandoned because the sound of exterior audible device at 39 , in fig3 draws the attention of onlookers or passerbys or others at the scene . in yet another scenario , an operator is approaching their car in a parking lot or pumping gas at a gas station , when a carjacker demands the car threatening the operator with a gun . the operator wisely turns over the keys and lets the carjacker occupy the operator &# 39 ; s seat at 56 in the vehicle 64 . at this times the occupancy sensor at 61 , in fig5 will senda signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking sequence at 32 in fig2 and the hazard lights at 18 will began to flash continuously at 35 notifying the operatorthe carjacking attempt will be foiled in the same manner as described above . in a different scenario , the operator is stopped waiting for a traffic light to change when a carjacker forces his way by gunpoint into the passenger seat of the vehicle 64 and demands that the operator drive the vehicle or forces the operator into the trunk of the vehicle 64 the operator merely complies with the carjackers demand knowing that the vehicle 64 will be disabled at 32 , in fig2 as the pressure sensors at 57 , 61 , and 63 in fig5 send a signal to the command control unit 7 that an unauthorized occupant has entered the vehicle 64 . the command control unit 7 will then automatically initiate the anti - carjacking disabling sequence at 33 in fig3 . at this time the hazard lights 18 will begin to flash at 35 , in fig3 and after a pre - determined amount of time , for example , 60 seconds the vehicle 64 will be disabled at 36 , 37 and 38 and audible devices 19 will sound at 39 compelling the carjacker from the vehicle 64 . still another scenario is where the vehicle 64 is occupied by two authorized occupants . one at sensor 59 and one at sensor 61 . both sensors 59 and 61 , in fig5 are of the pressure sensor type illustrated in fig4 . both sensors 59 and 61 are programmed into the memory of the command control unit 7 . the authorized occupants stop at a late night party store at 1 : 30 a . m . the occupant at 59 exits the vehicle 64 to go into the party store . leaving the occupant at 61 in the vehicle . pressure sensor 60 is set to sense an unauthorized occupancy . while the authorized occupant at pressure sensor 59 is in the party store an unauthorized occupant enters the vehicle 64 at sensors 59 and 60 and attempts to make the occupant at sensor 61 drive the vehicle at gunpoint . within seconds after the unauthorized occupant enter the vehicle 64 the pressure sensors at 59 and 60 send signals to the command control unit 7 that an unauthorized occupant is in the vehicle 64 . the command control unit 7 automatically initiates the disabling sequence , at 33 in fig3 which prevents the vehicle 64 from leaving the scene and prevents a possible hostage scenariowhere the authorized occupant may have been forced to drive their own vehicle to some isolated location where the carjacker may do harm to an authorized occupant and go unnoticed . in yet another scenario , a carjacker watches and stalks a potential victim leave their vehicle 64 and go into the supermarket to shop . as the potential victim returns to and is sitting in their vehicle . the carjackerapproaches the vehicle preparing to attempt the carjacking . as the carjacker approaches the vehicle he notices an emblem obviously displayingthe fact the vehicle 64 is equipped with the present invention . the carjacker realizing that he will not be able to drive away with vehicle 64aborts his attempt and seeks another vehicle not so equipped . finally , referring to fig1 the command control unit 7 responds to sensorinputs by controlling actuators or relays 22 according to programmed instructions . the sensors 21 provide input to the command control unit 7 about vehicle occupancy , engine and vehicle conditions and the command control unit 7 initiates the appropriate response . by way of example , if the ignition sensor 2 indicates that the ignition is on and the shift lever position sensor 4 indicates a parked condition , the pressure sensors1 indicate a no occupancy condition and the rpm sensor 3 indicates the engine is running the command control unit 7 will allow an authorized operator to idle the engine for purposes of warming the engine in necessary weather conditions . the authorized operator need not be in the vehicle 64 for the engine to idle . upon initial startup the pressure sensor 61 , in fig5 sends a signal to the command control unit 7 that anauthorized occupant is in the vehicle . thus , after startup the authorized occupant may exit the vehicle 64 and the vehicle 64 will continue to idle . however , if the carjacker attempts to enter the vehicle while it is idling and the authorized occupant is not in the vehicle the pressure sensor 61 will send a signal to the command control unit 7 that an unauthorized occupant is in the vehicle 64 and will automatically initiate the disablement sequence at 33 in fig3 . thus it will be demonstrated that there is a vehicular automatic occupant sensing anti - carjacking system which achieves the various objectives , features and considerations of the present invention and which is well adapted to meet the conditions of mass production and practical usage . as various changes might be made in the exemplary embodiments above described and shown without departing from the spirit of the invention andas various changes might be made in the embodiment set forth , it is to be understood that all matter herein described or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense . the spirit and scope of the present invention are to be limited only by theterms of the appended claims .", "category": "General tagging of new or cross-sectional technology"}
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Is the patent correctly categorized?
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b645029c1cf919f8965ce8e991f7c3758ab7a1adb26db05d59ea35a9623ef0ec
| 0.652344 | 0.035156 | 0.730469 | 0.114258 | 0.832031 | 0.162109 |
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Electricity"}
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Human Necessities"}
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Is the category the most suitable category for the given patent?
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0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.001244 | 0.00002 | 0.007813 | 0.001205 | 0.046631 | 0.012024 |
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{"category": "Electricity", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Performing Operations; Transporting"}
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Does the category match the content of the patent?
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0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.339844 | 0.168945 | 0.703125 | 0.378906 | 0.796875 | 0.242188 |
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Electricity"}
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{"category": "Chemistry; Metallurgy", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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Is the category the most suitable category for the given patent?
| 0.25 |
0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.001411 | 0.02124 | 0.007813 | 0.018555 | 0.046631 | 0.038574 |
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{"category": "Electricity", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Textiles; Paper"}
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Is the category the most suitable category for the given patent?
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0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.239258 | 0.000261 | 0.12793 | 0.000626 | 0.636719 | 0.004913 |
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Electricity"}
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{"category": "Fixed Constructions", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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Does the patent belong in this category?
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0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.006897 | 0.174805 | 0.02478 | 0.78125 | 0.018799 | 0.710938 |
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Electricity"}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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Does the category match the content of the patent?
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0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.005066 | 0.035645 | 0.03418 | 0.034668 | 0.039063 | 0.394531 |
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "Electricity"}
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{"category": "Physics", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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Is the categorization of this patent accurate?
| 0.25 |
0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.002808 | 0.396484 | 0.012817 | 0.894531 | 0.066406 | 0.84375 |
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{"category": "Electricity", "patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above ."}
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{"patent": "fig1 to 3 were already discussed above . fig4 illustrates the constellation of the pol - qam 6 / 4 modulation scheme as an exemplary embodiment of the inventive modulation scheme . in addition to the 4 sops each having 4 phase constellation points in case of pdm - qpsk ( see fig3 ), in pol - qam 6 / 4 two additional polarizations states ( see sop 5 and sop 6 in fig4 ) are added which do not lie in the plane defined by sop 1 - sop 4 . thus , pol - qam 6 / 4 uses 6 sops each having 4 iq - constellation points . here , the linear 0 \u00b0 ( te ) and 90 \u00b0 ( tm ) states of polarization are used as additional states of polarization . however , the entirety of sop 1 - 6 may be rotated on the sphere such that the relative distance between the states of polarization remains the same . e . g . in case the two polarization components forming the pol - qam 6 / 4 signal exhibit a phase offset \u03c8 between each other , sop 1 - 4 are rotated around the s 1 axis in fig2 ( with a rotation of 2 \u00b7 \u03c8 ). symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 4 . symbol = sop x \u00b7( e j0 , e j\u03c0 / 2 , e j\u03c0 , e j3\u03c0 / 2 ), with x = 1 , . . . , 6 . however , preferably , the phase states of sop 5 and sop 6 are rotated by 45 \u00b0 compared to the phase states in sop 1 - sop 4 ( see fig3 ), i . e . the phase states are not identical for sop 1 - sop 4 and sop 5 - sop 6 . it can be shown that this increases the euclidian distance between the different symbols . the additional sops 5 and 6 ( here corresponding to te and tm output waves ) extend the alphabet of symbols from 16 symbols ( 4 sops each having 4 iq constellation points ) to 24 symbols ( 6 sops each having 4 iq constellation points ). hence , the maximum information which can be carried by a symbol increases from log 2 16 = 4 bits / symbol to log 2 24 = 4 . 58 bits / symbol . it should be noted that the inventive modulation scheme is not limited to 4 initial phases ( as in case of qpsk ) per state of polarization and may use a higher number of phases , e . g . 8 phases in case of 8 psk or 12 phases in case of 16 - qam ( quadrature amplitude modulation ). in case of 8 phases , the inventive method provides 8 sops on the great circle 10 and the two additional sop 5 and sop 6 outside the great circle 10 . thus , also sops different to the 6 sops discussed so far , can form the signals for the symbol alphabet , e . g . 8 sops not lying on a common great circle or 4 sops forming a tripod on the ps . fig5 illustrates the inverse of the euclidian distance for all combinations of two symbols in case of pm - qpsk ( see left diagram ) and in case of pol - qam 6 / 4 ( see right diagram ). the symbol alphabet for pm - qpsk comprises 16 symbols , thus , the left diagram shows 16 \u00b7 16 bars , whereas the symbol alphabet of pol - qam 6 / 4 comprises 24 symbols resulting in 24 \u00b7 24 bars in the right diagram . the right diagram for pol - qam 6 / 4 shows no bars higher than the bars in the left diagram for pol - qam . the same maximum heights of the bars prove the same minimum euclidian distance in both cases . thus , the osnr penalty remains unchanged when moving from pm - qpsk to pol - qam 6 / 4 . thus , pol - qam 6 / 4 extends the number of possible symbols from 16 to 24 without degradation of the osnr sensitivity . there exist many alternatives to map a number of information bits on the optical wave states forming the symbol alphabet . in the following a simple mapping of 9 information bits on two consecutive symbols ( which form a super symbol ) is explained in exemplary manner . in this case the transmitted information rate is 9 bits / 2 symbols = 4 . 5 bits / symbol . this value is slightly below the maximum achievable value of 4 . 58 bits / symbol . a wave state of a super symbol comprising two consecutive symbols \u2014 symbol 1 and symbol 2 \u2014 is formed by the orthogonal te , tm polarization components x 1 , y 1 of symbol 1 and the orthogonal te , tm polarization components x 2 , y 2 of symbol 2 . both polarization components are combined in a polarization beam combiner of the transmitter ( see combiner 3 in fig1 ). the waves x 1 , y 1 , x 2 , and y 2 are modulated by iq - modulators ( see iq - modulator 2 a and 2 b in fig3 ). two bits b 1 and b 2 may determine the complex output wave of a polarization component by iq ( b 1 , b 2 )=( b 1 \u2212 0 . 5 )+ j ( b 2 \u2212 0 . 5 ). iq ( b 1 , b 2 ) describes a qpsk constellation point with the amplitude 1 . table 1 below shows the mapping of 9 bits b 0 - b 1 to an optical super symbol formed by two consecutive optical symbols . in the transmitter mapping table e . g . the term \u201c x 1 \u201d in iq x1 ( b 1 , b 2 ) indicates that for symbol 1 the te (= x ) polarization is modulated by a qpsk constellation point determined by the bits b 1 and b 2 . in case that one of the additional sops ( sop 5 and sop 6 ) is excited ( i . e . the transmitter output signal carries either only a te ( x ) or a tm ( y ) polarization component , y 1 / 2 = 0 or x 1 / 2 = 0 ), the amplitude of the associated iq - modulator is increased by the factor of \u221a{ square root over ( 2 )} to keep the signal power at the same level (= 1 ) as for the pdm - qpsk modulation . as evident from tab . 1 , only one of the two symbols within a super symbol may be in sop 5 or sop 6 . with this mapping of two bits to an iq constellation the decision in the receiver becomes easy . at the receiver , the following decisions are performed : di 1 =| x 1 |\u2212| y 1 | and di 2 =| x 2 |\u2212| y 2 |, with di 1 , 2 denoting the difference between the signal amplitude ( magnitude ) of x 1 , 2 and y 1 , 2 . each difference result di 1 , 2 is in one of three states . thus , di 1 , 2 is 0 if sop 1 - 4 are transmitted ( fig3 ), and di 1 , 2 is + 1 or \u2212 1 if sop 5 - 6 are transmitted . the decision process at the receiver is illustrated in tab . 2 . the decision in the receiver may be realized in a dsp . the decision process is based on determining and analyzing di 1 , 2 . in case both di 1 and di 2 are 0 , then b 0 = 0 and only sop 1 - 4 are used for both symbols of the super symbol . in this case e . g . the two bits b 1 , b 2 are determined by the decision dec ( x 1 ). the term \u201c dec ( x 1 )\u201d denotes the two decisions required to extract the two bits b 1 and b 2 from the received constellation point transported by the component wave x 1 , i . e . b 1 = result of ( re ( x 1 )& gt ; 0 ) and b 2 = result of ( im ( x 1 )& gt ; 0 ). similarly , the other bits b 3 - b 8 are determined . in case of di 1 \u2260 0 or di 2 \u2260 0 , b 0 corresponds to 1 , i . e . one of sop 5 and 6 were used for one symbol of the current super symbol . further , one has to check whether di 1 \u2260 0 or alternatively di 2 \u2260 0 . in case di 1 \u2260 0 , b 1 corresponds to 0 . alternatively , b 1 corresponds to 1 . in dependency of the value of di 1 , 2 also b 2 is decided ( see third column in tab . 2 ). the remaining bits b 3 - b 8 are determined as indicated in the fourth to seventh columns . a first embodiment of a transmitter for generating an optical signal modulated between all 6 sops is illustrated in fig6 . the pol - qam 6 / 4 transmitter in fig6 is based on the pm - qpsk transmitter in fig1 and e . g . may be configured to transport 40 gb / s or 100 gb / s data rates . figurative elements in fig1 and 6 denoted by the same reference signs are basically the same . in addition to the elements in fig1 , the pol - qam 6 / 4 transmitter comprises an intensity modulator 20 which is configured to selectively dim one of the two optical waves fed to the optical polarization combiner 3 . in fig6 the intensity modulator 20 is realized as an mzi and intensity modulation is performed upstream of the iq - modulators 2 a and 2 b , i . e . at the inputs of iq - modulators 2 a and 2 b . however , intensity modulation may be also performed downstream of the iq - modulators 2 a and 2 b . the intensity modulator 20 in fig6 has two complementary outputs , i . e . the intensity at the upper output fed to the upper modulator 2 a is complementary to the intensity at the lower output fed to the lower modulator 2 b . here , a three - state intensity modulator 20 is used , i . e . the modulator 20 modulates the two optical waves between 3 intensity states . in the 0 . 5 / 0 . 5 intensity state both waves have essentially the same ( high ) intensity , in the 1 / 0 intensity state the upper wave ( fed to the upper modulator 2 a ) has high intensity and the lower wave ( fed to the upper modulator 2 b ) has very low or zero intensity , and in the 0 / 1 intensity state the upper wave has very low or zero intensity and the lower wave has high intensity . preferably , in the 1 / 0 and 0 / 1 states the intensity modulator operates in saturation . in the 0 . 5 / 0 . 5 intensity state , the conventional polarization constellation points are selected ( see e . g . sop 1 - 4 in fig3 in case of qpsk modulation ). in the 1 / 0 and 0 / 1 intensity states , the two additional states of polarization are selected . if e . g . the upper path is assigned to the te polarization with 0 \u00b0 polarization angle and the lower path is assigned to the tm polarization with 90 \u00b0 polarization angle , dimming the upper wave ( 0 / 1 state ) results in sop 6 ( tm polarization ), whereas dimming the lower wave ( 1 / 0 state ) results in sop 5 ( te polarization ). similar to fig1 , the modulation encoder 4 \u2032 generates two binary signals d 1 - d 2 for controlling the upper iq - modulator 2 a and two binary signals d 3 - d 4 for controlling the lower iq - modulator 2 b . each pair of binary signals select a phase state from the four phase states of the qpsk constellation . the modulator encoder 4 \u2032 further generates the modulation signal d 5 fed to the intensity modulator 2 . the modulator signal d 5 is a three - state signal for selecting each of the three states . a second embodiment of a transmitter generating an optical signal modulated between all 6 sops is illustrated in fig7 . the pol - qam 6 / 4 transmitter in fig7 is based on the pm - qpsk transmitter in fig1 . figurative elements in fig1 and 7 denoted by the same reference signs are basically the same . in fig7 an additional optical polarization modulator 30 is provided downstream of the polarization combiner 3 . here , the polarization modulator is realized as a polarization switch 30 which switches to one of the additional sops . the polarization switch 30 is realized by using a switchable quarter wave plate ( qwp ) which is capable of converting \u2014 when activated \u2014 circular polarized light to linear polarized light . this is caused by the fact that in a qwp a polarization component of the light polarized along a fast axis propagates faster than the orthogonal polarization component polarized along the orthogonal slow axis . in a qwp this difference in speed results in a quarter wavelength phase shift between both polarization components . thus , by activating the qwp in the polarization switch 30 ( e . g . by switching the qwp in the light path ), the 90 \u00b0 phase shift between two orthogonal polarization components of a circular polarized wave ( see sop 2 or sop 4 in fig3 ) directly at the input of the polarization switch 30 may be compensated , resulting in a linear polarized wave at the output of the polarization switch 30 . for switching from sop 2 and sop 4 to sop 5 and sop 6 when activating the qwp , the qwp has to be arranged in such a way at the output of the polarization combiner 3 that the axes of the qwp are tilted by 45 \u00b0 compared to the orthogonal polarization components of the optical signal ( i . e . 45 \u00b0 polarized light would be coupled only in one of the axis of the qwp ). in dependency of the data to be transmitted , a modulation encoder 4 \u2033 generates modulation signals d 1 - d 5 . preferably , the modulations signals d 1 - d 5 are binary signals . the modulation encoder 4 \u2033 feds modulation signals d 1 - d 4 to the iq - modulators 2 a and 2 b and modulation signal d 5 to the polarization modulator 30 . the binary signal d 5 activates or deactivates the qwp in the polarization switch 30 as discussed above . for modulation of the pol - qam signal it is also an option to compute the optical fields e x and e y in the electrical domain and to generate the transmitter field via a field modulator . it is well known that a mzi with a phase modulator in its interferometer arms provides an optical output field proportional in field amplitude to the applied drive voltage d ( for small values of d ), provided the mzi is biased at zero ( no transmission for d = 0 ). e is proportional to sin ( a \u00b7 d ) if the magnitude of d is larger , \u201c a \u201d is a coefficient . this is further illustrated by the iq - modulator in fig8 . two mzis form two field modulators for the real ( i ) and imaginary ( q ) components of the field e = e i + j e q . the field amplitudes e i and e q are roughly proportional to the applied drive voltages di and dq , respectively . as shown in fig1 , 6 and 7 already discussed above , a combination of a second iq - modulator for the orthogonal polarization enables to modulate the orthogonal polarization , e . g . the first modulator provides e x = e x1 + j e xq for the x polarization and the second modulator provides e y = e y1 + j e yq for the orthogonal y polarization . the required drive voltages are d x1 , d xq , d y1 , and d yq respectively . the voltages d x1 , d xq , d y1 , and d yq can by computed in a digital ( dsp ) or analog electronic processor receiving the information bits . at the output of the processor time samples ( e . g . with symbol rate or with double symbol rate ) of all d x1 , d xq , d y1 , and d yq are provided . the voltages d x1 , d xq , d y1 , and d yq can be computed for example by using tab . 1 . iq x and iq y are already complex numbers which are proportional to the driving voltages d x1 , d xq , d y1 , and d yq and depend on two bits bi and bj : iq ( bi , bj )=( bi \u2212 0 . 5 )+ j ( bj \u2212 0 . 5 ). real and imaginary parts of iq x , y are proportional to d x , y1 and d x , yq , respectively . fig9 illustrates a third embodiment of a transmitter which is capable to modulate the output signal between all 6 sops and is based on the idea to compute the necessary optical fields e x and e y of both polarization components essentially in the electrical domain in the modulation encoder 4 \u2032\u2033. the modulation signals d 1 \u2032- d 4 \u2032 as generated by the modulation encoder 4 \u2032\u2033 are non - binary , analog signals . the iq - modulators 2 a and 2 b are operated in the analog domain . this corresponds to an ofdm transmitter which modulates an analog signal formed by the inverse fourier transform of the subchannel signals on the optical carrier . the inventive modulation scheme may be also used in connection with ofdm . accordingly , each subcarrier may be modulated using the additional states of polarizations sop 5 and sop 6 as indicated in fig3 . fig1 illustrates a conventional coherent pdm - ofdm transmission system comprising a pdm - ofdm transmitter and a pdm - ofdm receiver . data (\u201c x data \u201d) transmitted via the x polarization plane ( e . g . te ) and data (\u201c y data \u201d) transmitted via the y polarization plane are independently processed in separate transmitter paths associated to the two polarization planes . each transmitter path comprises a serial - to - parallel - converter 40 a / b , a coder 41 a / b , a i - fft - block 42 a / b for performing an inverse fast fourier transform , a parallel - to - serial - converter 43 a / b and two dacs 44 a - d ( digital - to - analog converter ) for the inphase ( denoted as \u201c i \u201d) and the quadrature ( denoted as \u201c q \u201d) components . the inphase and quadrature components of each polarization component x and y are modulated on an optical carrier by iq - modulators 45 a / b . the two orthogonal polarization components x and y are combined by a polarization combiner 46 . at the receiver , the polarization components x and y of the optical signal are completely separately processed . first , the polarization multiplexed signal is split into the orthogonal polarization components x and y by a polarization splitter 47 . thereafter , the polarization components x and y are split into the inphase and quadrature components by optical hybrids 48 a / b . the inphase ix and quadrature qx components of the polarization component x and the inphase iy and quadrature qy components of the polarization component y are converted to electrical signals by four photodiodes 49 a - d . downstream of the photodiodes 49 a - d are adcs 50 a - d ( analog - to - digital converters ), serial - to - parallel converters 51 a / b , two separate fft - blocks 52 a / b ( fast fourier transform ) for the x and y polarization components as well as separate decoders 53 a / b and parallel - to - serial converters 54 a / b . as indicated in the lower part of fig1 , for each subcarrier the x polarization and the y polarization are separately modulated according to a given phase constellation ( e . g . qpsk ). at the receiver , the x polarization component and the y polarization component are separately detected . since the polarization components x and y of the polarization splitter 47 are typically not aligned to the polarization components x and y at the transmitter , electronic polarization demultiplexing can be applied to recover the transmitted x signal and transmitted y signal . for this purpose , for each corresponding upper ( 52 a ) and lower ( 52 b ) subcarrier output of the fft a complex 2 \u00b7 2 matrix multiplication may be applied ( not shown ). this multiplication performs the polarization demultiplexing operation leading to an x subcarrier signal and a y subcarrier signal which are then fed to the respective decoders 53 a and 53 b where the x and y subcarrier signals are decided separately and independently . alternatively , optical polarization demultiplexing may be used ( not shown ) by aligning the polarization components x and y of the polarization splitter 47 to the polarization components x and y at the transmitter . fig1 illustrates an embodiment of a coherent ofdm transmission system with subcarrier modulation according to pol - qam . figurative elements in fig1 and 11 denoted by the same reference signs are basically the same . in fig1 the data to be transmitted is fed to a cascade of a serial - to - parallel - converter 40 \u2032 and a combined mapper / coder 41 \u2032. in the combined mapper / coder 41 \u2032 the necessary x and y polarization components are determined for generating an individual pol - qam signal per each subcarrier wavelength , preferably for generating a pol - qam 6 / 4 signal as discussed above . this is indicated in the lower part of fig1 by the polarization and phase constellation diagram of pol - qam 6 / 4 identical to the polarization and phase constellation diagram in fig4 . a pol - qam 6 / 4 subcarrier signal is formed by the combination of an x polarization component subcarrier and y polarization component subcarrier at the same frequency . the x and y components are transformed in the time domain by two i - fft - blocks 42 a / b . the remaining parts of the transmitter are identical to the transmitter in fig1 . at the receiver , the polarization components x and y of the optical signal are initially processed and demultiplexed as discussed in connection with fig1 . however , in contrast to the separate decoders 53 a / b in fig1 , the receiver in fig1 comprises a joint decoder 53 \u2032 for jointly deciding the x and y components forming a combined symbol per subcarrier . the joint decoder 53 \u2032 may be configured to jointly deciding two consecutive symbols per subcarrier , with the two consecutive symbols forming a super symbol as discussed above . the decoded subcarrier information is fed to a joint parallel - to - serial converter 54 \u2032 for recovering the original serial data stream . it should be noted that the embodiments of the invention as discussed above may be also configured for a higher number of phase states per symbol , e . g . 8 phases per symbol as in case of 8 psk . moreover , qam modulation instead of pure psk modulation may be used , in particular for the iq - modulators discussed above .", "category": "General tagging of new or cross-sectional technology"}
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Does the patent belong in this category?
| 0.25 |
0682a14968c1c4cbef7351f8f2c4af3539bf66887cc35e750f27cc19d213e51f
| 0.554688 | 0.200195 | 0.886719 | 0.90625 | 0.949219 | 0.08252 |
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{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Human Necessities"}
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Does the category match the content of the patent?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.025146 | 0.059326 | 0.098145 | 0.133789 | 0.163086 | 0.092773 |
null |
{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"category": "Chemistry; Metallurgy", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
|
Is the categorization of this patent accurate?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.014526 | 0.007813 | 0.049561 | 0.005737 | 0.212891 | 0.004456 |
null |
{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"category": "Textiles; Paper", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
|
Is the categorization of this patent accurate?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.014526 | 0.061768 | 0.049561 | 0.002548 | 0.21582 | 0.072754 |
null |
{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Fixed Constructions"}
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Is the categorization of this patent accurate?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.014526 | 0.091309 | 0.049561 | 0.128906 | 0.212891 | 0.445313 |
null |
{"category": "Performing Operations; Transporting", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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Does the patent belong in this category?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.068359 | 0.024414 | 0.048828 | 0.032471 | 0.613281 | 0.170898 |
null |
{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"category": "Physics", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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Is the categorization of this patent accurate?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.014526 | 0.12793 | 0.049561 | 0.375 | 0.212891 | 0.208984 |
null |
{"patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto .", "category": "Performing Operations; Transporting"}
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{"category": "Electricity", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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Does the category match the content of the patent?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.025146 | 0.005554 | 0.098145 | 0.014526 | 0.163086 | 0.02002 |
null |
{"category": "Performing Operations; Transporting", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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{"category": "General tagging of new or cross-sectional technology", "patent": "with reference to fig1 device 10 is the device of the claimed invention . the basic components of device 10 include ribs 11 - 17 , collar 18 and a clear flexible single - piece cover 20 . collar 18 is a thin circular structure having a circular aperture 22 in its center . the diameter of circular aperture 22 is about one - half that of the outer diameter of circular collar 18 . integrally connected to collar 18 is an arm 24 having the same thickness as collar 18 and having a length approximately equal to the inside diameter of collar 18 . attached to opposite portions of collar ribs 11 - 17 . as shown in fig . 6 each rib 11 - 17 has an arcuate portion 26 and a pair of linear segments 28 . linear segments 28 are constructed so that a first end 30 of each linear segment 28 is integrally attached to the arcuate portion of an associated rib . the second ends 32 and 33 of the pair of linear segments 28 of each rib face each other , and with the linear segments 28 of an associated rib , lie in a plane that includes the arcuate portion of the rib . the ribs may be constructed of metal and may be of a gauge similar to the wire used to construct clotheshangers . ends 32 and 33 of each linear segment 28 of ribs 11 - 17 are hingedly attached to diametric points on the periphery of the collar . for instance the collar may have attached to its surface a first series of knuckles ( not shown ) and a second series of knuckles ( not shown ). the second series of knuckles are diametrically positioned on the collar relative to the first . the ends 32 and 33 of ribs 11 - 17 are used as pintles . ends 32 of ribs 11 - 17 are inserted into the first series of knuckles and ends 33 of ribs 11 - 17 are inserted into the second series of knuckles , and the ends 32 and 33 are rotatable within the knuckles , and hingedly connect ribs 11 - 17 to collar 18 . alternatively , sockets may be drilled into the sides of the collar and ends 32 and 33 of ribs 11 - 17 may be rotatably seated within the sockets . as seen in fig . 1 rib 14 is located on the collar so that its apex 36 lies approximately above the center of aperture 22 of collar 18 . in this position linear segments 28 , of rib 14 , have their ends 32 and 33 attached approximately on or near a diameter of circular collar 18 and a folding hinge line 19 . ribs 13 and 15 have their linear segments 28 attached to collar 18 so that these linear segments are parallel to , and positioned on either side of the linear segments of ribs 14 ; linear segments 13 and 15 are spaced an equal linear distance from the linear segment of rib 14 . although the linear segments of ribs 13 and 15 are parallel to one another the planes defined by the linear segments , and the arcuate portions of each of these ribs are not parallel as apexes 36 of ribs 13 and 15 are spaced a greater distance from one another than are their respective linear segments . ribs 16 and 12 are fastened to the collar on either side of rib 14 at points which lie approximately two times the linear distance from the linear segments of rib 14 than do the linear segments of ribs 13 and 15 . the planes defined by the linear segments and the arcuate portions of ribs 12 and 16 are not parallel to one another as apexes 36 of these ribs are also spaced a greater linear distance from one another than their respective linear segments . ribs 11 and 17 also have linear segments with ends 32 and 33 attached to the periphery of collar 18 . the ends 32 and 33 of ribs 11 and 17 are positioned at an equal distance from either side of the linear segments of rib 14 at points which are spaced approximately three times the linear distance from linear segments 28 of rib 14 than are the linear segments of ribs 13 and 15 . the apexes of ribs 11 and 17 lie at about a forty - five degree angle relative to the apex of rib 14 and therefore these two ribs lie in approximately the same substantially horizontal plane perpendiucular to the plane defined by rib 14 . the collar 18 and the ribs 11 - 17 form a supporting substructure or a framework for single - piece cover 20 which is transparent and flexible . the cover may be a laminate composed of different plastics or of the same plastic . alternatively , the cover may be formed of only one sheet of plastic . plastic such as polyethylene , polypropylene or polyethylene terephthalate may be used . the cover lies over the supporting ribs and may be attached , for example by staples , velcro fasteners , or snap fasteners to the underside of collar 18 . as seen from fig . 1 , the structure described is a semi - circular structure having a cavity 38 . access is permitted to the cavity through aperture 22 , and two bottom slits 53 and two tops slits 55 . bottom slits 53 are used by the individual within cavity 38 . these slits allow one to perform self - grooming services . bottom slits 53 have overlapping rubber flaps ( not shown ) to seal the slits when the individual within cavity 38 withdrawals his hands from cavity 38 . top slits 55 may be parallel neighboring slits formed in a midportion of single - piece cover 20 located between any of ribs 11 - 17 . a barber gains access to cavity 38 by placing his hands through top slits 55 as shown in fig . 1 and 2 . on the outside surface of cover 20 , positioned over top slits 55 , as shown in fig . 2 , are a plurality of overlapping rubber flaps 65 . rubber flaps 65 seal slits 55 to maintain a slight vacuum in cavity 38 when the barber removes his arms from cavity 38 . although not deoicted , the overlapping flaps may form a structure that resembles the iris of diaphram in a single lens reflex camera . collar 18 , as discussed above , has an arm 24 integrally connected thereto . the arm 24 is a support for vacuum hose 40 ( fig1 and 2 ) and for air filter 42 and breathing tube 44 . vacuum hose 40 as seen more clearly in fig2 is attached at a first end to the vacuum side of a vacuum pump 45 . a portion of vacuum hose 40 is supported by passing it through a hole in arm 24 , and an open end of the hose is positioned in cavity 38 defined by collar 18 , ribs 11 through 17 and cover 20 . the section or open area of arm 24 between vacuum hose 40 and arm 24 may be packed with suitable material to seal the area where the hose protrudes therethrough to help maintain a slight vacuum within cavity 38 . the air filter 42 is composed of a perforated plastic structure having a porous - cover , for example a cloth cover . the filter is tapered at its neck for positioning the filter through a hole in arm 24 as shown . breathing tube 44 is fastened to the neck of the filter which secures air filter 42 to arm 24 . breathing tube 44 includes mouth piece 46 to be used as shown in fig2 . although not depicted , the overlapping flaps may form a structure that resembles the iris diaphram in a single lens reflex camera . as seen in fig4 the collar may be formed of two half sections 54 and 56 , wherein arm 24 is integrally connected at a midpoint of the collar about one quarter the circumferential distance of the collar from the linear segments 28 of rib 14 . in a first embodiment the two half sections 54 and 56 are connected to one another by hinges . these hinges are constructed of material similar to the material sold under the trademark velcro , and therefore the hinge pieces can be quickly and easily disconnected from one another . the hinges ( not shown ) are positioned on the underside of collar 18 across hinge line 19 . in a second embodiment , the two half sections 54 and 56 of collar 18 are connected by a pivot pin 58 . by this construction a first end of half section 56 of collar 18 lies above a first end of half section 54 . when the collar sections are brought together to form aperture 22 , the second end of half section 56 also lies above the second end of half section 54 . the half sections at their non - pivotally connected ends may be connected by a pin or other fastener device ( not shown ). in order to gain access to device 10 to cut hair , in accordance with the first embodiment , ribs 15 - 17 are folded in one direction as shown in fig4 and ribs 11 - 14 are folded in an opposing direction , relative to ribs 15 - 17 . the two velcro type hinges are released and the astronaut receiving the hair cut positions his neck between collar half sections 54 and 56 which are then rejoined by the velcro type fasteners . to gain access to device 10 to cut hair , the velcro hinges , in accordance with the first embodiment are removed or the pin connecting the second ends of the collar halves , in accordance with the second embodiment , is removed . as shown in fig4 the collar is opened by rotating collar half section 54 in the direction of arrow 60 . cover 20 is constructed of a sufficient amount of material to accommodate such movement . the astronaut positions his neck within the opening of the collar , under the cover , and then the collar half sections are closed about his neck . the hinges are replaced or the removed pin is then replaced to connect the second ends of half sections 54 and 56 . thereafter the ribs are unfolded returning them to their position shown in fig1 . in embodiments one and two the astronaut &# 39 ; s head is positioned within cavity 38 as shown in fig2 and 3 . in embodiments one or two the device 10 has a flexible circular seal flap 62 ( e . g ., a rubber flap ) attached to the circumference of the inside diameter of collar 18 . seal flap 62 as shown in fig4 has two half sections , each section being secured to an associated collar half section . when the half sections of the collar , 54 and 56 are closed about the astronauts neck seal flap 62 conforms to the contour of the astronauts neck maintaining the slight vacuum cavity 38 . alternatively , the astronaut receiving the hair cut may be fitted with a separate flexible plastic or rubber cylindrically - shaped collar ( not shown ). this collar is fastened about the neck of the astronaut and is attached at its top portion to the top or bottom portion of collar 18 and secured thereto . a bottom portion of the cylindrically shaped collar is draped around the persons neck and the cylindrically shaped collar has a skirt with a drawstring . the string is tightened in a comfortable manner to seal the aperture and to help maintain the slight vacuum within cavity 38 relative to the cabin . to cut the barber or groomer places his arms through top slits 55 in cover 20 parting overlapping rubber flaps 65 ; the astronaut places the mouthpiece 46 of the breathing tube 44 in his mouth , and the barber , by manipulating scissors and a comb , is able to cut the astronaut . the astronaut can cut his own hair , or shave his facial hair by putting his own arms through bottom slits 53 ( fig1 ) in the bottom of single - piece cover 20 . as hair clippings are produced the vacuum hose 40 , connected to the vacuum pump , which is operating to create a reduced pressure atmosphere within the cavity relative to the cabin , quickly and cleanly disposes of the clippings . in view of reduced gravity in space the device is easily rotated about the astronauts neck so that the device essentially follows the muscle movements of the baber as shown in fig2 and 3 . both astronaut and barber can be completely secured within the cabin by placing their feet through stirrups 67 shown in fig2 and 3 . the astronaut is also preferably restrained in a seated position . the device may also be used to collect the aerosol droplets of hair spray or small powder residue and the residue of other cosmetics which otherwise would float freely throughout the cabin if applied to an individual not using the present invention . a manicure can be conducted using the device of the invention . to recieve such a service the astronaut places his hands through aperture 22 of the collar 18 parting seal flap 62 , and the manicurist , by placing his hands through top slits 55 of flexible cover 20 , can clip the nails and cuticles of an astronaut . the nail and cuticle clippings thus produced can be quickly disposed of via vacuum hose 40 within cavity 38 . when the device is used as a manicure station , the air filter can be removed and an appropiate support can be inserted in place of the air filter to elevate the device or support the device so the astronaut receiving the manicure can rest comfortably . hair cutting tools and / or manicure tools may be releasably attached , for example by magnets , or velcro type fasteners , to the top surface of collar 18 as illustrated by scissors 63 in fig1 . the device 10 of the invention has low mass and is portable and can be easily and quickly stored within the crew cabin . for instance , after grooming activities are concluded , and the astronaut is removed from the device , ribs 11 - 17 are folded in the direction of arrow 61 of fig5 and collar half section 54 is folded along hinge line 19 , to collapse device 10 . vacuum hose 40 is disconnected from the collapsed device aand the device is then placed in container 62 and stored in cabinet 64 as shown in fig5 . while the device of the instant invention has been described and illustrated , it should be apparent that many modifications may be made thereto without departing from the spirit and scope of the invention . accordingly , the disclosed invention is not limited by the foregoing description , but is only limited by the scope of the claims appended hereto ."}
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Does the patent belong in this category?
| 0.25 |
a65d671a6ddb2e644bfa8065bccb787314f7f8a3dea2c0a4519fa8dabfc95a30
| 0.069336 | 0.279297 | 0.048828 | 0.511719 | 0.613281 | 0.546875 |
null |
{"category": "Chemistry; Metallurgy", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Human Necessities"}
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Does the patent belong in this category?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.178711 | 0.007813 | 0.683594 | 0.004333 | 0.785156 | 0.010681 |
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Chemistry; Metallurgy"}
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{"category": "Performing Operations; Transporting", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
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Is the categorization of this patent accurate?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.019775 | 0.002121 | 0.195313 | 0.00103 | 0.376953 | 0.02063 |
null |
{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Chemistry; Metallurgy"}
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{"category": "Textiles; Paper", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
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Does the category match the content of the patent?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.287109 | 0.018311 | 0.287109 | 0.009705 | 0.275391 | 0.02478 |
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Chemistry; Metallurgy"}
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Fixed Constructions"}
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Is the patent correctly categorized?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.010681 | 0.047363 | 0.271484 | 0.075684 | 0.378906 | 0.427734 |
null |
{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Chemistry; Metallurgy"}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
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Is the categorization of this patent accurate?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.020386 | 0.004059 | 0.19043 | 0.003479 | 0.376953 | 0.055908 |
null |
{"category": "Chemistry; Metallurgy", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Physics"}
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Is the patent correctly categorized?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.226563 | 0.010986 | 0.777344 | 0.030273 | 0.730469 | 0.263672 |
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{"category": "Chemistry; Metallurgy", "patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto ."}
|
{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Electricity"}
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Does the patent belong in this category?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.178711 | 0.000519 | 0.683594 | 0.000828 | 0.785156 | 0.001244 |
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "Chemistry; Metallurgy"}
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{"patent": "\u03b2 - lapachone , as well as its intermediates , derivatives and analogs thereof ( also referred to herein as the \u201c active compounds \u201d), are described in li , c . j . et al ., j . biol . chem ., 1993 . unlike prior art \u03b2 - lapachone syntheses as illustrated in scheme 1 , the synthesis of \u03b2 - lapachone , in accordance with the present invention and generally illustrated in scheme 2 , commences with the reaction of 2 - hydroxy - 1 , 4 - naphthoquinone with 1 - bromo - 3 - methyl - 2 - butene in the presence of sodium iodide and triethylamine ( a weak base ) in dimethylsulfoxide ( dmso ) to produce lapachol in up to 40 % yield , after purification ( 20 g , up to 40 % overall yield ). lapachol is then quantitatively converted to \u03b2 - lapachone by treatment with sulfuric acid . the \u03b2 - lapachone is purified by recrystallization from ethanol . any impurities detected by thin layer chromatography ( tlc ), nuclear magnetic resonance spectroscopy ( nmr ) or hplc ( high pressure liquid chromatography ) can be removed by addition of repeated crystallization steps . with reference to fig1 and discussed in greater detail in the examples section below , the synthetic process for preparing the \u03b2 - lapachone intermediate , lapachol , commences with the preparation of a reaction mixture comprised of 2 - hydroxyl - 1 , 4 - napthoquinone , 1 - bromo - 3 - methyl - 2 - butene , triethylamine ( tea ) and dimethylsulfoxide ( dmso ). this reaction mixture is first stirred at room temperature under a noble gas atmosphere for about one hour . the reaction mixture is then heated and subsequently cooled to stop the reaction the mixture is then extracted three times with ch 2 ci 2 ( e . g ., 500 ml , 300 ml , 200 ml ) and the organic phases pooled and successively washed with water , followed by two washings with 5 % sodium bicarbonate ( nahco 3 ) and one washing with 1 % sodium chloride ( nacl ). the organic phase is then dried with sodium sulfate ( na 2 so 4 ) and the filtrate , after filtration , is evaporated by rotovap . the residue is then dissolved in toluene heated in a water bath at 50 \u00b0 c . and any existing insoluble material is filtered off . the resulting toluene solution is then extracted three times with 2 n naoh ( e . g ., 800 ml , 300 ml , 200 ml ). the resulting combined aqueous phase is then neutralized with 220 ml concentrated hydrochloric acid ( hcl ) and the mixture is extracted three times with toluene ( e . g ., 500 ml , 300 ml , 300 ml ). the organic phases are then pooled and any ( black ) solids existing in the organic phase is removed by filtration . once filtered , the combined organic phase is then washed successively with 1 % nacl , 5 % aqueous sodium bicarbonate and 1 % aqueous sodium chloride , the resulting organic phase is then dried with sodium sulfate and the resulting filtrate is evaporated by rotovap to dryness , followed by the addition of isopropanol for co - evaporation to completely remove residual toluene . the residue is then dissolved in isopropanol , heated and then cooled . pure lapachol is obtained after filtering washing with cold isopropanol and drying under vacuum . with reference to fig2 and discussed in greater detail in the examples section below , the synthesis of \u03b2 - lapachone from lapachol commences with preparation of a reaction mixture comprised of the pure lapachol ( 30 g ) in 300 ml of sulfuric acid . the reaction mixture is stirred at room temperature for 30 minutes and poured into ice water with manual stirring . the mixture is then extracted twice with toluene ( e . g ., 600 ml and 400 ml ) to provide a combined organic phase , which is then washed successively with 800 ml of 1 % nacl , 400 ml of 1 % nahco 3 and 800 ml of 1 % nacl . the resulting organic phase is then dried with 50 g na 2 so 4 and the solid is filtered off . tolune in the remaining filtrate is then evaporated off by rotovap and co - evaporated following the addition of ethanol to completely remove residual toluene . the residue is then dissolved in either 75 % ethanol or absolute ethanol , preferably absolute ethanol , heated in an 80 \u00b0 c . water bath and then filtered and cooled to 4 \u00b0 c . pure \u03b2 - lapachone is then isolated by filtration and washed with cold 75 % ethanol ( 4 \u00b0 c . 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . the invention is further defined by reference to the following examples . it will be apparent to those skilled in the art that many modifications , both to the materials and methods , may be practiced without departing from the purpose and interest of the invention . into a dried 2 , 000 ml round bottomed flask was added 2 - hydroxy - 1 , 4 - napthoquinone ( 69 . 7 g , 0 . 40 mol ), 1 - bromo - 3 - methyl - 2 - butene ( 66 g , 0 . 44 mol ), sodium iodide ( 60 g , 0 . 4 mol ), triethylamine ( 58 . 55 ml , 0 . 42 mol ) and dimethylsulfoxide ( dmso ), 500 ml . the mixture was stirred vigorously at room temperature under argon atmosphere for 1 hour , then heated with a heating mantle to 45 \u00b0 c . after 3 - 6 hours , at 45 \u00b0 c . with vigorous stirring , the mixture was cooled down in an ice bath , and 800 ml of water was added to stop the reaction . the mixture is then transferred into a 2 , 000 ml separatory funnel and extracted three times with methylene chloride ( 500 ml , 300 ml and 200 ml ). the organic phases were pooled and washed successively with water ( 800 ml ), 5 % aqueous sodium bicarbonate ( 2 \u00d7 800 ml )* and 1 % aqueous sodium chloride ( 800 ml ), then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap . the residue was dissolved in toluene ( 1 , 000 ml ) with heating in a 50 \u00b0 c . water bath , and any insoluble material existing was filtered off . the warm toluene solution was extracted three times with freshly prepared , warm 2n sodium hydroxide ( 800 ml , 300 ml and 200 ml ). the aqueous phases were pooled and neutralized by addition of hydrochloric acid ( 220 ml ) with vigorous manual stirring , then extracted three times with toluene ( 500 ml , 300 ml and 300 ml ). the organic phase were pooled and any black solid existing in the organic phases was removed by filtration . the combined organic phase was washed successively with 1 % aqueous sodium chloride ( 800 ml ), 5 % aqueous sodium bicarbonate ( 500 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap , then isopropanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in isopropanol ( 300 ml ) with heating in an 80 \u00b0 c . water bath and then was cooled to 4 \u00b0 c . slowly . pure lapachol was obtained after filtering , washing with cold isopropanol ( 4 \u00b0 c ., 50 - 100 ml ) and drying under vacuum . during the 5 % aqueous sodium bicarbonate extractions , significant amounts of precipitate ( 2 - hydroxy - 1 , 4 - naphthoquinone ) appeared between aqueous phase and organic phase . the precipitate along with organic layer was separated from aqueous layer for the first extraction , but the precipitate was separated from both aqueous and organic layers for the second extraction , and was transferred into a 500 ml separatory funnel ; 5 % aqueous sodium bicarbonate ( 150 ml ) and methylene chloride ( 150 ml ) were added into the 50 ml separatory funnel . after shaking , the organic phase was separated and pooled with the major organic phases before extraction with 1 % aqueous sodium chloride . into a 1 , 000 ml beaker containing sulfuric acid ( 300 ml ), lapachol ( 30 g , 0 . 124 mol ) was added in portions slowly over 5 minutes at room temperature while stirring vigorously . after addition , the dark mixture was stirred for an additional 30 min and then poured into ice water ( 800 g ) with manual stirring in a 2 , 000 ml beaker . the mixture was transferred into a 2 , 000 ml separatory funnel and extracted twice with toluene ( 600 ml and 400 ml ). the toluene phases were pooled and washed successively with 1 % aqueous sodium chloride ( 800 ml ), 1 % aqueous sodium bicarbonate ( 400 ml ) and 1 % aqueous sodium chloride ( 800 ml ), and then dried with sodium sulfate ( 50 g ). after filtration , the filtrate was evaporated to dryness by rotovap and then ethanol ( 300 ml ) was added for co - evaporation to completely remove residual toluene . the residue was dissolved in 75 % ethanol or absolute ethanol , preferably absolute ethanol ( ethanol / water , 3 : 1 , 300 ml ) with heating in an 80 \u00b0 c . water bath , then was filtered and cooled to 4 \u00b0 c . slowly . pure \u03b2 - lapachone was isolated by filtration , then washed with cold 75 % ethanol ( 4 \u00b0 c ., 100 ml ), dried under vacuum , packed under argon atmosphere and stored at \u2212 20 \u00b0 c . in the dark . routine procedures were used for melting point measurement , hplc analysis and nmr analysis . melting point and nmr data reported in literature were used for comparison with obtained data ( see tables 2 and 3 below ). for hplc analysis , a linear gradient from 25 % to 75 % buffer ( methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 55 : 20 )) in 10 min at a flow rate of 1 ml / min was applied , and the sample was prepared by dissolving lapachol or \u03b2 - lapachone in methanol at a concentration of 2 mg / ml and then diluting it in methanol / acetonitrile / 0 . 1 % phosphoric acid ( 25 : 20 : 55 ) to 10 \u03bcg / ml for 10 to 100 \u03bcl injections . methanol was fisher scientific cat # a452 - 4 . acetonitrile was fisher scientific cat # a998sk - 4 . phosporic acid was baker cat # 0260 - 03 . the bplc column used was a nova - pak c18 ( 5 micron ), 3 . 9 \u00d7 150 mm ( waters part no . wat086344 )., and the iplc system used was a beckman 126n solvent module / 168nm detector / system gold . in the lapachol synthesis , a weak organic base , triethylamine ( tea ) was used ( pyridine may also be used ) instead of strong inorganic bases such as potassium hydroxide or lithium hydroxide as used in prior art lapachol syntheses to trap the acid generated from the reaction between the quinone and bromide compound ( see schaffner - sabba , k ., et al ., \u03b2 - lapachone : synthesis of derivatives and activities in tumor models , j . med . chem ., 27 , ( 1984 ) 990 - 994 ; sun , j . s . et al ., a preparative synthesis of lapachol and related naphthoquinones , tetrahedron letters , 39 ( 1998 ) 8221 - 8224 ). observation showed that use of a weak organic base simplified the procedures and enhanced the yield ( see scheme 1 above and table 1 below ), thus reducing production costs . the second step of the synthesis , conversion of the lapachol to \u03b2 - lapachone , was shown to be relatively simple and resulted in high yield ( more than 90 %). the analytical data shown in table 2 ( melting point data for lapachol and \u03b2 - lapachone ) and table 3 ( nmr data for \u03b2 - lapachone ) confirm the identity of the synthesized compounds . hplc analysis of starting material ( 2 - hydroxy - 1 , 4 - naphtoquinone ), lapachol and \u03b2 - lapachone prepared in accordance with the present method are more than 99 % pure . see fig3 a - 3 e . while there have been shown and described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof , it will be understood that various omissions and substitutions and changes in the form and details of the disclosed invention may be made by those skilled in the art without departing from the spirit of the invention . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto .", "category": "General tagging of new or cross-sectional technology"}
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Does the category match the content of the patent?
| 0.25 |
e8b7cece9dee1b21e94e0893314f602513c52c41f865759bb4d06e0efd679b7b
| 0.287109 | 0.304688 | 0.296875 | 0.057373 | 0.275391 | 0.084961 |
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Performing Operations; Transporting"}
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Human Necessities"}
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Does the patent belong in this category?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.020996 | 0.003281 | 0.024048 | 0.048828 | 0.265625 | 0.129883 |
null |
{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Performing Operations; Transporting"}
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Chemistry; Metallurgy"}
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Is the patent correctly categorized?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.013611 | 0.001244 | 0.054199 | 0.027954 | 0.21582 | 0.035645 |
null |
{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Performing Operations; Transporting"}
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Textiles; Paper"}
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Is the patent correctly categorized?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.013611 | 0.000912 | 0.054199 | 0.002884 | 0.21582 | 0.00592 |
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{"category": "Performing Operations; Transporting", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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{"category": "Fixed Constructions", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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Is the patent correctly categorized?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.04541 | 0.074707 | 0.026001 | 0.296875 | 0.427734 | 0.380859 |
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{"category": "Performing Operations; Transporting", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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Is the patent correctly categorized?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.04541 | 0.039551 | 0.02478 | 0.055908 | 0.427734 | 0.578125 |
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{"category": "Performing Operations; Transporting", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Physics"}
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Does the patent belong in this category?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.047363 | 0.010681 | 0.018555 | 0.154297 | 0.478516 | 0.400391 |
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Performing Operations; Transporting"}
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{"patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art .", "category": "Electricity"}
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Is the category the most suitable category for the given patent?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.011658 | 0.000444 | 0.032471 | 0.092773 | 0.198242 | 0.030273 |
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{"category": "Performing Operations; Transporting", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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{"category": "General tagging of new or cross-sectional technology", "patent": "an ampule cutting apparatus in accordance with the present invention will now be described in detail with reference to the accompanying drawings . fig3 a is a perspective view illustrating the ampule cutting apparatus in accordance with the present invention , and fig3 b is a schematic side - sectional view illustrating the inside structure of the ampule cutting apparatus in accordance with the present invention . referring to fig3 a and 3b , the ampule cutting apparatus includes a box - shaped housing 10 , a cyclone object collecting unit 20 disposed at the top inside portion of the housing 10 , and an ampule cutting unit 30 . the cyclone object collecting unit 20 is configured to suck and collect a cut ampule head h and flakes ( hereinafter referred to individually and collectively as \u2018 objects \u2019). the ampule cutting unit 30 , for housing and cutting the ampule head h , is linked and coupled to an intake port 21 of the cyclone object collecting unit 20 . in addition , the ampule cutting apparatus includes collecting units 40 and 60 for collecting the objects sucked by the cyclone object collecting unit 20 and a vacuum motor 50 for supplying a negative pressure to the cyclone object collecting unit 20 . the collecting units 40 and 60 and the vacuum motor 50 are installed inside the housing 10 . the constitutional elements of the ampule cutting apparatus will now be explained in detail with reference to the accompanying drawings . fig4 is a partial perspective view illustrating a protruding unit for housing a suction tube in the housing of fig3 a , and fig5 is a partial cross - sectional view illustrating an inclination angle of the bottom surface of the protruding unit of fig4 . the ampule cutting unit 30 is installed at the top inside portion of the housing 10 . in this case , the protruding unit 11 is formed on the top front surface of the housing 10 , for covering the ampule cutting unit 30 protruded from the upper portion in the forward direction . as illustrated in fig4 and 5 , the bottom surface 12 of the protruding unit 11 has an angle \u03b8 of substantially 5 to 85 \u00b0, preferably , 30 to 60 \u00b0 to the horizontal plane . the angle \u03b8 of protruding unit 11 helps the user to set the appropriate hand moving range in the ampule cutting operation . that is , the ampule a cutting direction is the direction towards the front surface of the housing 10 as shown in fig5 . when the user cuts the ampule a by pushing an ampule body b in the cutting direction , his / her hand is inwardly bent and fixed to the front surface of the housing 10 . therefore , the user can safely and easily cut the ampule a . preferably , the angle \u03b8 of the bottom surface 12 can be appropriately adjusted among the suggested angles in consideration of the size of the ampule a or other factors . fig6 is a disassembled cross - sectional view illustrating the ampule cutting unit of the ampule cutting apparatus in accordance with the present invention . fig7 is a perspective view illustrating a nozzle of fig6 . fig8 is a perspective view illustrating the ampule inserted into the nozzle of fig6 . fig9 is a partial cross - sectional view illustrating the front end of the nozzle of fig8 . fig1 a and 10b are schematic cross - sectional views illustrating a state where the ampule is inserted into the ampule cutting unit and a state where the ampule is cut by the ampule cutting unit , respectively . as shown in fig3 b and 6 , the ampule cutting unit 30 includes a suction tube 31 , a fixing unit 330 , and a nozzle 310 . the suction tube 31 has one end detachably coupled to the intake port 21 of the cyclone object collecting unit 20 and another end detachably coupled the nozzle 310 via the fixing unit 330 . as depicted in fig1 a , the nozzle 310 is inserted into the suction tube 31 through a through hole 331 of the fixing unit 330 . an outer circumference of a front end 321 of the nozzle 310 and an outer circumference of a protruding jaw 323 are pressed in a first inner circumference 333 and a second inner circumference 335 of the fixing unit 330 , respectively . here , the nozzle 310 pressed in the fixing unit 330 is not any more inserted by the fixing jaw 337 . in the ampule cutting unit 30 , the nozzle 310 and the fixing unit 330 for fixing the nozzle 310 can be easily replaced according to the capacity or shape of the ampule a . a main suction hole 311 is formed in the nozzle 310 in the longitudinal direction . a plurality of auxiliary suction holes 313 for linking the main suction hole 311 to the outside space of the nozzle 310 are inclinedly formed around the front end 321 of the nozzle 310 . the main suction hole 311 has a diameter larger than the ampule head h and smaller than the ampule body b , thereby preventing the ampule body b from being sucked into the cyclone object collecting unit 20 by the negative pressure generated in the nozzle 310 by the vacuum motor 50 in the ampule cutting operation . the inner circumference of the main suction hole 311 has a streamline shape corresponding to the shape of the ampule head h , for stably supporting the ampule a and minimizing the cutting force in the ampule cutting operation . that is , as shown in fig9 a and 10 b , the front end of the main suction hole 311 , namely , a shoulder positioning surface 316 a is formed to correspond to the shoulder s of the ampule a , thereby stably supporting the ampule a inserted into the main suction hole 311 . in addition , the rear end of the main suction hole 311 , namely , a head positioning surface 316 b is formed to correspond to the head h of the ampule a . in a state where the ampule head h is inserted into the main suction hole 311 to cut the ampule a ( refer to fig1 a ), if the ampule body b is pushed to the front surface of the housing 10 ( refer to fig1 b and 5 ), one side of the shoulder s of the ampule a is supported by the shoulder positioning surface 316 a , and the other side of the head h of the ampule a is supported by the head positioning surface 316 b . the ampule a having its two points supported can be easily cut by a small force . on the other hand , as shown in fig9 , the plurality of auxiliary suction holes 313 are inclinedly formed around the front end 321 of the nozzle 310 on which the inserted ample neck n is positioned , for sucking minute flakes generated at the cutting part in the ample head h cutting operation . preferably , the inclination angle of the plurality of auxiliary suction holes 313 ranges from about 15 to 75 \u00b0 to the longitudinal direction of the nozzle 310 according to the shape and size of the ampule a . in the case that the cut ampule head h does not pass through the main suction hole 311 but blocks the main suction hole 311 , the plurality of auxiliary suction holes 313 serve to prevent overheating of the vacuum motor 50 . fig1 a and 11b are cross - sectional views illustrating states before and after the suction tube is coupled to the intake port of the cyclone object collecting unit through a pair of coupling rings , respectively . referring to fig1 a , the ampule cutting unit 30 is detachably coupled to the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 . the first coupling ring 341 is fixedly coupled to one end of the intake port 21 , and the second coupling ring 343 is coupled to the suction tube 31 . the first and second coupling rings 341 and 343 have a protruding unit 341 a and a groove 343 a , and are detachably coupled to each other as shown in fig1 b . preferably , the first and second coupling rings 341 and 343 are made of a sealing material , for example , a rubber material . the ampule cutting unit 30 can be disconnected from the intake port 21 of the cyclone object collecting unit 20 through the first and second coupling rings 341 and 343 , and thus easily cleaned and repaired . it is thus easy to remove alien substances from the suction tube 31 . fig1 is a schematic perspective view illustrating an ultraviolet sterilizing unit of the ampule cutting apparatus in accordance with the present invention , fig1 a is a side view illustrating the ultraviolet sterilizing unit of fig1 , and fig1 b is a rear view , seen from i direction of fig1 a . as illustrated in fig1 , the ampule cutting apparatus includes the ultraviolet sterilizing unit 70 installed adjacently to the suction tube 31 , for sterilizing the suction tube 31 and the nozzle 310 contaminated by the injection contained in the ampule a . the ultraviolet sterilizing unit 70 includes an ultraviolet lamp 73 ( consumed power : 3 to 4 watts ) disposed adjacently to the suction tube 31 , a pair of supporting members 71 coupled to the inside portion of the housing 10 , for supporting the ultraviolet lamp 73 , and a grill unit 75 formed at the part of the suction tube 31 adjacent to the ultraviolet lamp 73 . as shown in fig1 a and 13b , the grill unit 75 is preferably formed to correspond to the ultraviolet lamp 73 , for sterilizing the suction tube 31 and the nozzle 310 by the ultraviolet rays emitted from the ultraviolet lamp 73 . preferably , suction tube 31 includes transparent ultraviolet transmission members 77 sealed therein . the transparent ultraviolet transmission members 77 allow the ultraviolet light from the ultraviolet lamp 73 into the suction tube . for example , transparent ultraviolet transmission members 77 can be made of transparent fluorine - containing polymers such as teflon . preferably , the positions of the grill unit 75 and the ultraviolet lamp 73 are appropriately varied by the position of the nozzle 310 varied by the cutting position of the ampule a . fig1 is a schematic disassembly perspective view illustrating a first collecting vessel of the ampule cutting apparatus in accordance with the present invention , and fig1 a and 15b are side views illustrating open and close states of a discharge plate of the first collecting vessel of fig1 . the collecting units 40 and 60 include the first collecting vessel 40 and the second collecting vessel 60 . the first collecting vessel 40 is detachably coupled to the bottom end of the cyclone object collecting unit 20 . the second collecting vessel 60 collects the objects collected in the first collecting vessel 40 for final disposal . the first collecting vessel 40 primarily collects the objects sucked into the cyclone object collecting unit 20 , and discharges a predetermined amount of objects to the lower direction when the vacuum motor 50 stops the operation . the second collecting vessel 60 finally collects the objects discharged from the first collecting vessel 40 . a door 15 formed on the housing 10 as shown in fig3 a is opened to empty the second collecting vessel 60 . the structure of the first collecting vessel 40 will now be explained in detail . as illustrated in fig1 , the first collecting vessel 40 includes a body 41 and a discharge plate 45 . the body 41 has its top end detachably coupled to the bottom end of the cyclone object collecting unit 20 . the discharge plate 45 is elastically hinge - coupled to one side of the bottom end of the body 41 and , thus , is configured for opening or closing the bottom end of the body 41 . first and second protrusions 42 a and 42 b are formed on the bottom end of one surface of the body 41 at predetermined intervals . third and fourth protrusions 47 a and 47 b corresponding to the first and second protrusions 42 a and 42 b are formed on one side of the discharge plate 45 . as depicted in fig1 and 15 a , the first to fourth protrusions 42 a , 42 b , 47 a and 47 b are hinge - coupled to each other by a hinge rod 49 passing through coupling holes 43 a , 43 b , 48 a and 48 b formed on the first to fourth protrusions 42 a , 42 b , 47 a and 47 b , respectively . the discharge plate 45 is elastically hinge - coupled to the body 41 by first and second torsion springs 46 a and 46 b coupled to the hinge rod 49 . the first torsion spring 46 a is positioned between the first protrusion 42 a and the third protrusion 47 a , and the second torsion spring 46 b is positioned between the second protrusion 42 b and the fourth protrusion 47 b . as shown in fig1 a , the first and second torsion springs 46 a and 46 b include a first fetch line 461 fixed to fixing protrusions 471 and 472 , and a second fetch line 463 elastically supported on one surface 41 a of the body 41 . still referring to fig1 a , the first collecting vessel 40 normally closes the bottom end of the body 41 by the elastic force of the first and second torsion springs 46 a and 46 b . when the suction force is generated by the operation of the vacuum motor 50 , the first collecting vessel 40 prevents reduction of the suction force by closing the bottom end of the body 41 by the discharge plate 45 . in addition , in a state where the vacuum motor 50 stops the operation , when the amount of the objects is over a reference amount , namely , when the weight of the objects is over the elastic force of the first and second torsion springs 46 a and 46 b , the first collecting vessel 40 freely drops the objects by opening the bottom end of the body 41 by rotating one side of the discharge plate 45 around the hinge rod 49 as shown in fig1 b . after all the objects collected in the first collecting vessel 40 are freely dropped , the discharge plate 45 returns to the original position of fig1 a by the first and second torsion springs 46 a and 46 b . here , the reference amount for discharging the objects can be adjusted by varying the specifications of the torsion springs , namely , elastic coefficients or winding numbers . the objects freely dropped from the first collecting vessel 40 are collected in the second collecting vessel 60 . preferably , the vacuum motor 50 disposed between the first and second collecting vessels 40 and 60 is appropriately covered not to interfere with the objects dropped from the first collecting vessel 40 . the operation of the ampule cutting apparatus in accordance with the present invention will now be described in detail . in a state where the vacuum motor 50 is operated , the ampule head h is inserted into the main suction hole 311 of the nozzle 310 as shown in fig1 a . when the ampule body b is pushed to the front surface of the housing 10 as shown in fig5 and 10 b , one side of the shoulder s of the ampule a is supported in the two points of the shoulder positioning surface 316 a , so that the ampule head h can be cut around the ampule neck n . the cut ampule head h is sucked into the cyclone object collecting unit 20 through the main suction hole 311 along the suction tube 31 . the minute flakes generated at the cutting part in the ampule head h cutting operation are sucked into the cyclone object collecting unit 20 through the plurality of auxiliary suction holes 313 and the main suction hole 311 along the suction tube 31 . the objects sucked into the cyclone object collecting unit 20 with the air are collected in the first collecting vessel 40 as shown in fig3 b , and the air contaminated by object is filtered by a general filter ( not shown ) installed in the cyclone object collecting unit 20 , sucked into the vacuum motor 50 through an exhaust port 23 and an exhaust path p , and externally discharged . on the other hand , while the suction operation is carried out by the vacuum motor 50 , if the amount of the objects collected in the first collecting vessel 40 exceeds the reference amount , the discharge plate 45 of the first collecting vessel 40 is rotated to the lower direction to open the bottom end of the first collecting vessel 40 . therefore , the objects accumulated on the discharge plate 45 are freely dropped to the second collecting vessel 60 . after most of the objects collected in the first collecting vessel 40 are dropped to the second collecting vessel 60 , the discharge plate 45 returns to the state of fig1 a by the first and second torsion springs 46 a and 46 b , thereby closing the bottom end of the first collecting vessel 40 . in this embodiment , two torsion springs are used , but one or more than two torsion springs can be used according to the needed elastic force . as discussed earlier , in accordance with the present invention , the ampule cutting apparatus can optimize suction of the ampule head and the flakes , by obtaining the smooth suction path by forming the main suction hole and the plurality of auxiliary suction holes on the nozzle into which the ampule head is inserted . in addition , the ampule cutting apparatus can easily cut the ampule with the minimum force , by forming the main suction hole of the nozzle in the streamline shape to correspond to the ampule head , and appropriately setting the installation angle of the ampule cutting unit in consideration of the ampule cutting angle . furthermore , the ampule cutting apparatus can maintain the wide suction path , optimize suction efficiency and prevent overheating of the vacuum motor , by easily cleaning the suction tube and removing alien substances from the suction tube by freely connecting or disconnecting the suction tube . finally , the ampule cutting apparatus can improve suction efficiency of the vacuum motor by setting the two steps of collecting vessels , reduce noises generated in the collecting operation of the cyclone object collecting unit , and sterilize the nozzle or suction tube contaminated by the injection by using the ultraviolet sterilizing unit . the foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention . the present teaching can be readily applied to other types of apparatuses . also , the description of the embodiments of the present invention is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art ."}
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Is the categorization of this patent accurate?
| 0.25 |
59c48d4cb35de505b6a9bcf7c6f253b0482cfe3ca6c96894fb9c053407f6c91a
| 0.029297 | 0.369141 | 0.018555 | 0.632813 | 0.277344 | 0.277344 |
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{"category": "Human Necessities", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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{"patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention .", "category": "Performing Operations; Transporting"}
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Is the patent correctly categorized?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.061035 | 0.062988 | 0.007813 | 0.028442 | 0.039063 | 0.275391 |
null |
{"category": "Human Necessities", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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{"category": "Chemistry; Metallurgy", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Does the category match the content of the patent?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.066406 | 0.012024 | 0.002472 | 0.243164 | 0.043457 | 0.230469 |
null |
{"patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention .", "category": "Human Necessities"}
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{"patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention .", "category": "Textiles; Paper"}
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Is the patent correctly categorized?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.009399 | 0.003708 | 0.002396 | 0.000504 | 0.010315 | 0.001595 |
null |
{"patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention .", "category": "Human Necessities"}
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{"category": "Fixed Constructions", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Is the patent correctly categorized?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.009399 | 0.036133 | 0.002319 | 0.030273 | 0.010315 | 0.092773 |
null |
{"patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention .", "category": "Human Necessities"}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Is the category the most suitable category for the given patent?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.022949 | 0.000805 | 0.001755 | 0.000149 | 0.032471 | 0.009155 |
null |
{"category": "Human Necessities", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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{"category": "Physics", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Is the patent correctly categorized?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.06543 | 0.021973 | 0.007813 | 0.035156 | 0.039063 | 0.161133 |
null |
{"category": "Human Necessities", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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{"category": "Electricity", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Does the category match the content of the patent?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.066406 | 0.003708 | 0.002472 | 0.003601 | 0.043457 | 0.007355 |
null |
{"category": "Human Necessities", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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{"category": "General tagging of new or cross-sectional technology", "patent": "the term &# 34 ; analyte &# 34 ; means any chemical or elemental compound of clinical and / or medical , environmental , or industrial significance and for which quantitative or qualitative measurements may be desired . examples of specific analytes are well known and include analytes of clinical significance such as glucose , hemoglobin , lipids , cholesterol , proteins , etc . other analytes will be readily apparent to those skilled in the art . a preferred biological compound is glucose . the present disclosure provides an apparatus and method for enhancing the transdermal transport of analytes . as illustrated in fig1 an apparatus of the invention generally consists of a sampling device 10 comprising a ultrasonic source 12 , a pressure reducing source 14 , a pressure boundary 16 which , together with a surface 20 of a body part , contains a sampling region 18 , and an analysis device 22 . any ultrasonic source 12 is suitable for use in the present invention . preferably , the source is an ultrasonic transducer capable of generating ultrasonic energy at a frequency range suitable for optimum extraction of glucose , e . g ., 20 khz to 1 mhz . the pressure reducing source 14 is capable of reducing pressure in the sampling , region 18 to an absolute pressure of about 400 mmhg , a vacuum pump is preferred . in one embodiment , the pump is powered by normal movements , such as the self - actuated pump described in u . s . patent application ser . no . ( not yet available ; atty docket number 5845 . us . 01 , filed dec . 18 , 1995 ). the pressure boundary 16 maintains a pneumatic seal against the surface 20 of the body , and may be any of a variety of well known materials suitable for this purpose , e . g ,., adhesive tape or an elastomeric ring . in those embodiments where analysis of analyte in sampling region 18 is provided , analysis of collected sample is provided by analysis element 22 located adjacent or , as shown in fig1 in contact with sampling region 18 . analysis element 22 is used to determine the presence or amount of at least one analyte of interest and the particular features of analysis element 22 are not critical to the invention . thus , any analyte detection method , sensor , or system suitable for use with the analyte of interest , for example optical or electrochemical sensors known in the art , may be used in analysis element 22 . an example of a suitable analysis device is an interference - free biosensor such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5843 . us . 01 , filed dec . 18 , 1995 ). the operation of a particular embodiment of the invention may be understood with reference to fig2 . the ultrasound source 12 generates ultrasonic energy directed at the body surface 20 . the transmission of this ultrasonic energy may be facilitated by the use of a coupling medium ( such as a gel ) within the sampling region 18 . the interaction of the ultrasonic energy with the body surface 20 increases the permeability of the skin at the body surface as described in current scientific literature ( mitragotri et al , j . pharm . sci . 84 : 697 - 706 , 1995 ). the pressure reducing , source 14 reduces the pressure in the sampling region 18 by removing air within the region 18 . note that the presence of a coupling medium within the region 18 should not affect the ability of the pressure reducing source 14 to reduce the pressure within the region 18 , and may in fact facilitate the pressure reduction by assisting in maintaining a seal between the pressure boundary 16 and the body surface 20 . any coupling medium should as well not interfere with the operation of the analysis device 22 . the combination of the enhanced permeability of the skin due to the ultrasonic energy and the pressure difference between the tissue and the sampling region will cause the enhanced flow of body fluid through the body surface 20 into the sampling region , where the concentration of the analyte is measured by the analysis device 22 . a second embodiment of the invention is illustrated in fig3 . in this embodiment pressure reducing source 14 is in vacuum connection with the pressure boundary 16 and the ultrasound source 12 and the analysis device 22 are contained within the sampling region 18 . such an arrangement facilitates ultrasound transmission , as the ultrasound source 12 may be directly coupled to the body surface 20 , if necessary with the local application of a coupling medium such as a gel . this arrangement also facilitates the measurement of the analyte , as the analysis device 22 is not affected by the coupling medium and may directly sense body fluid emerging from the body surface 20 . a third embodiment is illustrated in fig4 . two or more ultrasound sources 12 are placed on opposite sides of the pressure boundary 16 , so that they create a standing wave such as that described in u . s . patent application ser . no . not yet available ; atty docket number 5867 . us . 01 , filed feb . 23 , 1996 ) in the body surface 20 adjacent to the sampling region 18 . the reduced pressure source 14 reduces the pressure in the sampling region 18 . the combination of the ultrasound enhanced permeability of the skin and the difference in pressure between the tissue and the sampling region 18 causes fluid to exude from the body surface 18 . the concentration of the analyte of interest may then be measured by the analysis device 22 . all of the references cited in this application are incorporated by reference . the present invention has been described with reference to preferred and / or alternate embodiments . one of skill in the art will readily appreciate that changes , alterations or modifications can be made to these embodiments without departing from the true scope and spirit of the invention ."}
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Is the categorization of this patent accurate?
| 0.25 |
3bcb31da77599fcd103ff44965545dbf1e4f01eefda6c1bbddd42abd7cae1bcc
| 0.043457 | 0.245117 | 0.004761 | 0.189453 | 0.022949 | 0.263672 |
null |
{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Chemistry; Metallurgy"}
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{"category": "Human Necessities", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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Is the categorization of this patent accurate?
| 0.25 |
a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.0065 | 0.083984 | 0.095215 | 0.05835 | 0.157227 | 0.042725 |
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Chemistry; Metallurgy"}
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Performing Operations; Transporting"}
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Is the patent correctly categorized?
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a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.007355 | 0.000393 | 0.086426 | 0.017456 | 0.18457 | 0.090332 |
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{"category": "Chemistry; Metallurgy", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Textiles; Paper"}
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Is the category the most suitable category for the given patent?
| 0.25 |
a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.010986 | 0.000315 | 0.047363 | 0.000778 | 0.151367 | 0.009399 |
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{"category": "Chemistry; Metallurgy", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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{"category": "Fixed Constructions", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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Is the patent correctly categorized?
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a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.050293 | 0.039063 | 0.320313 | 0.353516 | 0.359375 | 0.359375 |
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Chemistry; Metallurgy"}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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Does the category match the content of the patent?
| 0.25 |
a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.102539 | 0.002716 | 0.219727 | 0.00193 | 0.211914 | 0.011353 |
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Chemistry; Metallurgy"}
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Physics"}
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Does the category match the content of the patent?
| 0.25 |
a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.102539 | 0.01001 | 0.219727 | 0.012024 | 0.211914 | 0.041504 |
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{"category": "Chemistry; Metallurgy", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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{"category": "Electricity", "patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :"}
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Is the categorization of this patent accurate?
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a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.031128 | 0.004456 | 0.168945 | 0.000755 | 0.150391 | 0.000687 |
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "Chemistry; Metallurgy"}
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{"patent": "a common procedure is used in the following examples 1 , 2 , and 3 , which relate to recombinant production of proteins identified as 2325p4 , 2325p6 , and 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 . this is procedure will be described first at a general level and then in more detail . thereafter , each example will be given . at a general level , fourteen oligonucleotides for each gene ( seven representing the top dna strand and seven for the bottom dna strand ) were synthesized . the oligonucleotides were cautiously designed so that : a ) after annealing , complementary oligonucleotides had an overhang at the 5 \u2032 end of each pair , each such overhang being 7 oligonucleotides long ; and b ) each such overhang had at least three nucleotide mismatches with the overhang of an unfitting pair of oligonucleotides . seven pairs of oligonucleotides , representing both strands of the full - length gene , were obtained after annealing . the duplex oligonucleotides were ligated in three steps to form full - length dna of the protein of interest . this full - length dna was then subjected to pcr . the pcr primers were chosen to : a ) incorporate a xbai restriction site at the 5 \u2032 end of the gene and a bamhi restriction site at the 3 \u2032 end of the gene . these sites were selected so the dna could be cloned into a pet - 11d plasmid vector at these sites . b ) include a translation initiation codon immediately before the first nucleotide of the gene . c ) incorporate a translation termination codon immediately after the last nucleotide of the final codon of the gene . the purified gene thus produced was inserted into a pet11d plasmid vector between xbai and bamhi restriction sites . the insert positive clones were identified and used to express recombinant protein . in each instance , the expressed protein had an additional methionine residue at position \u2212 1 . this was cleaved in vitro using aeromonas aminopeptidase to yield the desired protein . more specifically , in each instance fourteen oligonucleotides were synthesized and gel purified by genosys siotechnologies , inc . ( the woodlands , tex .). each oligonucleotide was phosphorylated at its 5 \u2032 end using t4 polynucleotide kinase enzyme and its reaction buffer from new england biolabs , inc . ( beverly , mass .). the desired dna was extracted with phenol : chloroform solution ( eastman kodak company , rochester , n . y .) and unincorporated ratp was removed by ethanol precipitation . each solution of complementary oligonucleotides ( 20 \u03bcg each , for a total of 40 \u03bcg ) was mixed and annealed to form duplex oligonucleotides . annealing was carried out by placing a tube containing the complementary oligonucleotides in a beaker containing boiling water and then transferring the beaker to a cold room for approximately 18 hours with gentle stirring . the annealed duplex oligonucleotides were then agarose gel purified using a jetsorb dna extraction kit from genomed inc . ( research triangle park , n . c .). the duplex oligonucleotides ( approximately 10 \u03bcg each ) were mixed and ligated together in three separate ligation steps at 16 \u00b0 c . for 18 hours using t4 dna ligase enzyme from new england biolabs , inc . ( beverly , mass .). as above , the dna in each ligation reaction mixture was precipitated with ethanol after extracting it with phenol : chloroform solution . this produced full - length double stranded dna of the protein of interest . this product , which was the desired gene , was amplified using pcr and purified from agarose gel using a jetsorb dna extraction kit . the purified gene was then digested with xbai and bamhi restriction enzymes followed by its ligation into a pet11d plasmid vector ( novagen ) that had also been digested with xbai and bamhi restriction enzyme from stratagene ( la jolla , calif .). ( it will be understood that the use of a pet11d vector , and of xbai and bamhi restriction sites , is only preferred and not necessary . another vector , and other restriction sites , could be used instead .) then , the ligated reaction mixture was used to transform e . coli strain xl1 - blue ( stratagene ) competent cells . the clones were identified for the insert dna of the desired protein in the plasmid dna preparations by restriction enzyme analysis . the recombinant plasmid dna was then used as described below to transform the expression host to express the target gene . e . coli bl21 ( de3 ) competent cells ( novagen , madison , wis .) were used as an expression host and transformed with the plasmid dna . ( another expression host could have been used instead .) the recombinant protein was expressed by induction with iptg . most of the expressed protein was found in the inclusion bodies and some was also present in the soluble fraction . to purify the recombinant protein , the bacterial pellet containing the inclusion bodies was resuspended , sonicated and centrifuged using the procedure of schultz and baldwin ( protein science 1 , 910 - 916 , 1992 ), modified as discussed below . the inclusion bodies were washed with 50 mm tris - hcl buffer , ph 8 . 5 containing 300 mm sodium chloride and centrifuged . the proteins present in the pellet were then denatured with 6 m guanidine - hcl in 100 mm tricine buffer , ph 8 . 5 . thereafter , the proteins were reduced and fully unfolded by adding 0 . 1 m reduced glutathione followed by incubation on at room temperature under nitrogen for 3 h . then , the proteins were refolded by 10 times dilution with nanopure water followed by incubation at 4 - 5 \u00b0 c . for 18 h . the refolded protein was then purified by cation exchange chromatography on sp - sepharose . the sp - sepharose column was eluted with a linear sodium chloride gradient ( 0 - 0 . 3 n ) in 0 . 15 m sodium acetate buffer , ph 5 . 0 . finally , the homogeneity of the purified proteins was checked by 10 - 20 % sds - polyacrylamide gel electrophoresis . although these steps were preferred to increase the yield of the desired protein , they are not necessary to the invention and may be omitted . finally , as stated above , the initial methionine residue at position 1 was cleaved in vitro by aeromonas aminopeptidase . this produced the desired protein . example 1 relates to a protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . in an initial step , oligonucleotides seq id no : 3 , seq id no : 4 , seq id no : 5 , seq id no : 6 , seq id no : 7 , seq id no : 8 , seq id no : 9 , seq id no : 10 , seq id no : 11 , seq id no : 12 , seq id no : 13 , seq id no : 14 , seq id no : 15 , and seq id no : 16 were synthesized and purified as discussed above . in the next step ( shown at the top of fig1 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 . these annealed oligonucleotides a1 , a2 , a3 , a4 , a5 , a6 , and a7 were then agarose gel purified as discussed above . the annealed and purified oligonucleotides were then mixed and ligated together in three separate ligation steps shown tin the center of fig1 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 3 and seq id no : 16 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted in a pet11d vector . the gene of the 2325p4 protein was agarose gel purified as discussed above . the purified 2325p4 gene was then digested with xbai and bamhi restriction enzyme and ligated into a pet11d plasmid vector as discussed above . then , as discussed above , the ligated reaction mixture was used to transform e . coli xl1 - blue competent cells , and the recombinant plasmid pet11d - 2325p4 dna was then used to transform the expression host to express the target gene as discussed above . the expressed protein has the amino acid sequence shown in seq id no : 59 , in which an additional n - terminal methionine residue is followed by lysine , the first amino acid of the 2325p4 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p4 recombinant protein having the amino acid sequence seq id no : 1 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p4 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 2 relates to a protein identified as 2325p6 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 17 and the nucleotide sequence of seq id no : 18 . in an initial step , oligonucleotides seq id no : 19 , seq id no : 20 , seq id no : 21 , seq id no : 22 , seq id no : 23 , seq id no : 24 , seq id no : 25 , seq id no : 26 , seq id no : 27 , seq id no : 28 , seq id no : 29 , seq id no : 30 , seq id no : 31 , and seq id no : 32 were synthesized and purified as discussed above . in the next step ( shown at the top of fig2 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 . these annealed oligonucleotides a8 , a9 , a10 , a11 , a12 , a13 , and a14 were agarose gel purified as discussed no above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig2 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 32 and seq id no : 33 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2325p6 protein , was purified from agarose gel and ligated into a pet - 11d plasmid vector at xbai and bamhi restriction site , all using the procedure discussed above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid pet11d - 2325p6 dna was used to transform the expression host ( e . coli bl12 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id nd : 60 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2325p6 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2325p6 recombinant protein having the amino acid sequence seq id no : 17 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2325p6 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . example 3 relates to a protein identified as 2728 in patent no . u . s . pat . no . 6 , 239 , 257 b1 , which has the amino acid sequence of seq id no : 34 and the nucleotide sequence of seq id no : 35 . in an initial step , oligonucleotides seq id no : 36 , seq id no : 37 , seq id no : 38 , seq id no : 39 , seq id no : 40 , seq id no : 41 , seq id no : 42 , seq id no : 43 , seq id no : 44 , seq id no : 45 , seq id no : 46 , seq id no : 47 , seq id no : 48 , and seq id no : 49 were synthesized and purified as discussed above . in the next step ( shown at the top of fig3 and described in detail above ), pairs of oligonucleotides were mixed and annealed to form duplex oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 . these annealed oligonucleotides a15 , a16 , a17 , a18 , a19 , a20 , and a21 were agarose gel purified as discussed above . the annealed oligonucleotides were mixed and ligated together in three separate ligation steps shown in the center of fig3 using the procedure described above . this produced full - length dna . 1 \u03bcg of the full - length dna was subjected to pcr with primers seq id no : 33 and seq id no : 49 . as discussed above , the primers provide xbai and bamhi restriction sites permitting the gene to be inserted into a pet11d plasmid vector . the double stranded full - length pcr product , namely the gene of the 2728 protein , was purified from agarose gel and ligated into a pet11d plasmid vector , all using the procedure described above . then , using the same procedure described above , e . coli xl1 - blue competent cells were transformed and the recombinant plasmid dna pet11d - 2728 was used to transform the expression host cell ( e . coli bl21 ( de3 ) competent cells ) to express the target gene . the expressed protein has the amino acid sequence shown in seq id no : 61 , in which an additional n - terminal methionine amino acid is followed by lysine , the first amino acid of the 2728 protein . the n - terminal additional methionine residue was cleaved as stated above to yield 2728 recombinant protein having the amino acid sequence seq id no : 34 . as stated in patent no . u . s . pat . no . 6 , 239 , 257 b1 , 2728 protein inhibited growth of human submaxillary gland carcinoma ( a - 253 ) cells and human bladder carcinoma ( t - 24 ) cells . as stated above , the protein identified as 2325p4 in patent no . u . s . pat . no . 6 , 239 , 257 b1 has the amino acid sequence of seq id no : 1 and the nucleotide sequence of seq id no : 2 . the process for making pet22b - 2325p4 dna is illustrated in fig4 . the above - described pet11d - 2325p4 plasmid dna ( consisting of 2325p4 dna cloned in a pet - 11d vector ) was used as a template for amplification using forward and reverse dna primers in pcr to produce 2325p4 dna in a form suitable for cloning into a pet22b plasmid between the msci and bamhi restriction sites . the forward primer , which is constructed to have seq id no : 50 , was designed to incorporate a msci restriction site at the 5 \u2032 end of the gene . the reverse primer , which is constructed to have seq id no : 10 , was designed to have a stop codon flanked by a bamhi site at the 3 \u2032 end of the gene . these primers were used in a single step of pcr amplification . the amplified dna was then digested with msci and bamhi restriction enzyme and cloned into pet22b plasmid digested with msci and bamhi restriction enzymes . the newly constructed plasmid was named pet22b - 2325p4 dna . pet11d - 2325p4a dna has been synthesized by replacing the isoleucine residue at position 44 of pet11d - 2325p4 dna with valine using site - directed mutagenesis . 2325p4a protein has the amino acid sequence of seq id no : 51 and the nucleotide sequence of seq id no : 52 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the isoleucine residue at position 44 to valine . the full - length gene off 2325p4a was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig5 , two separate pcr reactions were performed using pet11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 54 and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 53 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping region introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4a dna containing the desired mutation . then , the amplified full - length 2325p4a dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4a dna . recombinant 2325p4a protein was expressed and purified using e . coli bl21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 68 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 51 . this protein is active against a - 253 cells . commonly - owned patent no . u . s . pat . no . 6 , 175 , 003 b1 discusses the concept of \u201c cysteinizing \u201d therapeutically active rnases it would be advantageous to \u201c cysteinize \u201d the 2324p4 protein disclosed in the above - referenced &# 39 ; 257 patent to facilitate conjugation of a targeting moiety thereto . the 2325p4 protein has now been cysteinized by replacing the threonine residue at position 71 with cysteine using site - directed mutagenesis to form 2325p4 - cys71 , which has the amino acid sequence of seq id no : 55 and the nucleotide sequence of seq id no : 56 . primers were designed to generate dna fragments containing a ) an xbai restriction site at the 5 \u2032 terminus and b ) a stop codon flanked by a bamhi site at the 3 \u2032 terminus , and mismatched primers were synthesized to change the threonine residue at position 71 to cysteine . the full - length gene of 2325p4 - cys71 was made in two steps of pcr amplifications using a perkin elmer dna thermal cycler , pcr reagents and dna polymerase . in the first step of pcr amplification as shown in fig6 , two separate pcr reactions were performed using pet - 11d - 2325p4 dna as a template . in the first pcr reaction , amplification was carried out using primers seq id no : 33 and seq id no : 58 , and in the second pcr reaction , amplification was carried out using primers seq no id : 16 and seq id no : 57 . these two pcr reactions resulted in two overlapping dna fragments , both bearing the same mutation in the overlapping reaction introduced via primer mismatch . in the second step of pcr amplification , the two overlapping half - fragments were mixed together with primers seq id no : 33 and seq id no : 16 to produce full - length 2325p4 - cys7l dna containing the desired mutation . then , the amplified full - length 2325p4 - cys71 dna was gel purified and digested with xbai and bamhi restriction enzymes and subsequently cloned into pet - 11d plasmid cut with xbai and bamhi restriction enzymes . the newly constructed plasmid was named pet11d - 2325p4 - cys71 dna . recombinant 2325p4 - cys7l protein was expressed and purified using e . coli el21 ( de3 ) competent cells in the same way as described above in examples 1 , 2 , and 3 . the protein as expressed has the amino acid sequence of seq id no : 69 , with an initial methionine residue that is cleaved in vitro using aeromonas aminopeptidase to yield the protein having the amino acid sequence seq id no : 55 . this protein is active against a - 253 cells . quite obviously , a targeting moiety can be conjugated to the cysteine residue at position 71 of the 2325p4 - cys7l protein to direct it to a particular cell receptor of interest . the selection of an appropriate moiety is within the skill of a person skilled in the art . a fusion gene ( hege - linker - 2325p4 - cys71 dna ) cloned in pet22 plasmid vector has been synthesized and expressed . the recombinantly produced hegf - linker - 2325p4 - cys71 fusion protein has the amino acid sequence of seq id no : 70 and the nucleotide sequence of seq id no : 71 . a ) the sequence of hegf protein ( resides 1 to 53 ) b ) the sequence of the linker ( residues 54 to 62 ); and c ) the sequence or the 2325p4 - cys7l protein sequence ( residues 63 to 176 ) the full - length gene of hegf - linker - 2325p4 - cys71 was synthesized as shown in fig7 , using three steps of pcr amplification carried out using a perkin elmer dna thermal cycler , pcr reagents , and dna polymerase . pet22b - hegf dna and pet11d - 2325p4 - cys71 dna were used as templates for amplification . in the first step of pcr amplification , the plasmid pet22b - hegf dna was used as a template for amplification using primers seq id no : 72 and seq id no : 74 . the primer of seq id no : 74 has the c - terminal nucleotide sequence of hegf , followed by the nucleotide sequence of the linker . in the second step of pcr the plasmid pet11d - 2325p4 - cys71 dna was used as a template for amplification using primers seq id no : 16 and seq id no : 73 . as stated above , the primer of seq id no : 16 was designed to generate a stop codon flanked by a bamhi site at the 3 \u2032 terminus . the primer of seq id no : 73 contains the nucleotide sequence of the linker , followed by the n - terminal nucleotide sequence of 2325p4 - cys71 dna . these two pcr reactions resulted in two overlapping dna fragments in the third pcr step , these two overlapping fragments were mixed together with primer seq id no : 72 and seq id no : 16 to produce full - length hegf - linker - 2325p4 - cys71 dna . the amplified full - length hegf - linker - 2325p4 - cys71 dna was agarose gel purified as above , digested with bamhi restriction enzyme , and finally ligated into pet22b plasmid cut with msci and bamhi restriction enzymes . e . coli bl21 ( de3 ) competent cells were transformed with pet22b - hegf - linker - 2325p4 - cys71 plasmid dna and the recombinant protein was expressed and as in examples 1 , 2 , and 3 above . the protein as expressed has the amino acid sequence of seq id no : 70 . this protein is active against a - 253 cells . a surprising result occurred when the 2325p4 protein was expressed in e . coli bl21 ( de3 ) competent cells from pet22b - 2325p4 plasmid as discussed above in example 1 . four separate bioactive proteins were expressed , and all of them were active against a - 253 cells . the first of these was the 2325p4 protein , which has the amino acid sequence shown in seq id no : 1 . the second protein was the 2325p4 protein preceded by a two residue long leader sequence having the amino acid sequence of seq id no : 62 ( the second protein therefore has the amino acid sequence of seq id no : 63 ). the third protein was the 2325p4 protein preceded by a seven residue long leader sequence having the amino acid sequence of seq id no : 64 ( the third protein therefore has the amino acid sequence of seq id no : 65 ). the fourth protein was the 2325p4 protein preceded by a twenty - two residue long leader sequence having the amino acid sequence of seq id no : 66 ( the fourth protein therefore has the amino acid sequence of seq id no : 67 ). each of these leader sequences is derived from the pelb leader sequence of the pet22b vector . to a person skilled in the art , the fact that all four of these proteins remained active is very strong evidence that any protein protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the seven residue long leader sequence of seq id no : 64 in order will be active as well . and , the same is true of any protein made up of the 2325p4 protein preceded by at least one and at most all of the residues in the twenty two residue long leader sequence of seq id no : 66 in order . in other words , since the leader sequences of seq id no : 64 and seq id no : 66 did not affect the activity of the 2325p4 protein , any person ordinarily skilled in the art would expect that shortened versions of these leader sequences would , when likewise attached at the n - terminal end of the 2325p4 protein , leave the bioactivity of the 2325p4 protein unaffected . furthermore , given that the 2325p6 and 2728 proteins are also active against a - 253 and t - 24 cells , a person skilled in the art would conclude that adding all or any similarly - shortened shortened part of the seq id no : 64 or the seq id no : 66 leader sequences to the n - terminal end of the 2325p4 protein , to the n - terminal end of the 2325p6 protein , or to the n - terminal end of the 2728 protein , would also produce a bioactive protein . this is because these proteins are highly homologous and have highly similar activities against the same cancer cells . although one or more preferred embodiments have been described above , the invention is defined only by the following claims :", "category": "General tagging of new or cross-sectional technology"}
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Is the category the most suitable category for the given patent?
| 0.25 |
a9fc411b1ca4a66e5d6747ee6961a76d4c6b047fa95fc8c8bd5e0eec9c188da0
| 0.011353 | 0.109863 | 0.040283 | 0.398438 | 0.129883 | 0.259766 |
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{"category": "Human Necessities", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"category": "Performing Operations; Transporting", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 .", "category": "Human Necessities"}
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{"category": "Chemistry; Metallurgy", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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a4db778829b2230c015edcd82684f100765a2e5a3311beb1fa6fc30286f5993d
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{"patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 .", "category": "Human Necessities"}
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{"category": "Textiles; Paper", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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| 0.402344 | 0.773438 | 0.671875 | 0.746094 | 0.585938 | 0.267578 |
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{"category": "Human Necessities", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"category": "Fixed Constructions", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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a4db778829b2230c015edcd82684f100765a2e5a3311beb1fa6fc30286f5993d
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{"category": "Human Necessities", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 .", "category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting"}
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Is the categorization of this patent accurate?
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a4db778829b2230c015edcd82684f100765a2e5a3311beb1fa6fc30286f5993d
| 0.542969 | 0.036133 | 0.710938 | 0.081543 | 0.792969 | 0.22168 |
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{"category": "Human Necessities", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"category": "Physics", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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{"patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 .", "category": "Human Necessities"}
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{"category": "Electricity", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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Is the categorization of this patent accurate?
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a4db778829b2230c015edcd82684f100765a2e5a3311beb1fa6fc30286f5993d
| 0.08252 | 0.040283 | 0.130859 | 0.054932 | 0.261719 | 0.037842 |
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{"patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 .", "category": "Human Necessities"}
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{"category": "General tagging of new or cross-sectional technology", "patent": "we have found that lactobacillus salivarius strains ah102 , ah103 , ah105 , ah109 and ah110 are not only acid and bile tolerant and adhere to human intestinal cell lines but also , surprisingly have immunomodulatory effects , by modulating cytokine levels or by antagonising and excluding pro - inflammatory or immunomodulatory micro - organisms from the gastrointestinal tract . the general use of probiotic bacteria is in the form of viable cells . however , it can also be extended to non - viable cells such as killed cultures or compositions containing beneficial factors expressed by the probiotic bacteria . this could include thermally killed micro - organisms or micro - organisms killed by exposure to altered ph or subjection to pressure . with non - viable cells product preparation is simpler , cells may be incorporated easily into pharmaceuticals and storage requirements are much less limited than viable cells . lactobacillus casei yit 9018 offers an example of the effective use of heat killed cells as a method for the treatment and / or prevention of tumour growth as described in u . s . pat . no . 4 , 347 , 240 . it is unknown whether intact bacteria are required to exert an immunomodulatory effect or if individual active components of the invention can be utilized alone . proinflammatory components of certain bacterial strains have been identified . the proinflammatory effects of gram - negative bacteria are mediated by lipopolysaccharide ( lps ). lps alone induces a proinflammatory network , partially due to lps binding to the cd14 receptor on monocytes . it is assumed that components of probiotic bacteria possess immunomodulatory activity , due to the effects of the whole cell . upon isolation of these components , pharmaceutical grade manipulation is anticipated . interleukin - 8 ( il - 8 ) is one of the cytokines comprising the macrophage inflammatory protein family ( mip ). the mip - 1 and - 2 families represent a group of proteins which are chemotactic factors for leukocytes and fibroblasts . this family of proteins are also called intercrines , as cells other than macrophages are capable of synthesizing them . these cells include t and b cells , fibroblasts , endothelial cells , keratinocytes , smooth muscle cells , synovial cells , neutrophils , chondrocytes , hepatocytes , platelets and tumour cells . mip - 1\u03b1 , - 1\u03b2 , connective tissue activating protein ( ctap ), platelet factor 4 ( pf4 ) and il - 8 stimulate neutrophil chemotaxis . monocyte chemotactic protein ( mcp - 1 ) and rantes are chemotactic for monocytes , il - 8 for neutrophils and lymphocytes while pf4 and ctap are chemotactic for fibroblasts . roles other than chemotaxis have been described for some of these family members . mcp - 1 stimulates monocyte cytostatic activity and superoxide anion release . ctap and pf4 increase fibroblast proliferation , il - 8 increases vascular permeability while mip - 1\u03b1 and - 1\u03b2 are pyrogenic . il - 8 is intimately involved in inflammatory responses within the gastrointestinal tract . stimulation of il - 8 ( and other proinflammatory cytokines ) could contribute to the development of gastrointestinal lesions therefore it is important that probiotic bacteria should not stimulate the production of this cytokine . il - 10 is produced by t cells , b cells , monocytes and macrophages . this cytokine augments the proliferation and differentiation of b cells into antibody secreting cells . il - 10 exhibits mostly anti - inflammatory activities . it up - regulates il - 1ra expression by monocytes and suppresses the majority of monocyte inflammatory activities . il - 10 inhibits monocyte production of cytokines , reactive oxygen and nitrogen intermediates , mhc class ii expression , parasite killing and il - 10 production via a feed back mechanism ( 7 ). this cytokine has also been shown to block monocyte production of intestinal collagenase and type iv collagenase by interfering with a pge 2 - camp dependant pathway and therefore may be an important regulator of the connective tissue destruction seen in chronic inflammatory diseases . il - 12 is a heterodimeric protein of 70 kd composed of two covalently linked chains of 35 kd and 40 kd . it is produced primarily by antigen presenting cells , such as macrophages , early in the inflammatory cascade . intracellular bacteria stimulate the production of high levels of il - 12 . it is a potent inducer of ifn\u03b3 production and activator of natural killer cells . il - 12 is one of the key cytokines necessary for the generation of cell mediated , or th1 , immune responses primarily through its ability to prime cells for high ifn\u03b3 production ( 8 ). il - 12 induces the production of il - 10 which feedback inhibits il - 12 production thus restricting uncontrolled cytokine production . tgf - \u03b2 also down - regulates il - 12 production . il - 4 and il - 13 can have stimulatory or inhibitory effects on il - 12 production . inhibition of il - 12 in vivo may have some therapeutic value in the treatment of th1 associated inflammatory disorders , such as multiple sclerosis ( 9 ). interferon - gamma ( ifn\u03b3 ) is primarily a product of activated t lymphocytes and due to variable glycosylation it can be found ranging from 20 to 25 kda in size . this cytokine synergizes with other cytokines resulting in a more potent stimulation of monocytes , macrophages , neutrophils and endothelial cells . ifn\u03b3 also amplifies lipopolysaccharide ( lps ) induction of monocytes and macrophages by increasing cytokine production ( 10 ), increased reactive intermediate release , phagocytosis and cytotoxicity . ifn\u03b3 induces , or enhances the expression of major histocompatibility complex class ii ( mhc class ii ) antigens on monocytic cells and cells of epithelial , endothelial and connective tissue origin . this allows for greater presentation of antigen to the immune system from cells within inflamed tissues . ifn\u03b3 may also have anti - inflammatory effects . this cytokine inhibits phospholipase a 2 , thereby decreasing monocyte production of pge 2 and collagenase ( 11 ). ifn\u03b3 may also modulate monocyte and macrophage receptor expression for tgf\u03b2 , tnf\u03b1 and c5a ( 11 ) thereby contributing to the anti - inflammatory nature of this cytokine . probiotic stimulation of this cytokine would have variable effects in vivo depending on the current inflammatory state of the host , stimulation of other cytokines and the route of administration . tnf\u03b1 is a proinflammatory cytokine which mediates many of the local and systemic effects seen during an inflammatory response . this cytokine is primarily a monocyte or macrophage derived product but other cell types including lymphocytes , neutrophils , nk cells , mast cells , astrocytes , epithelial cells endothelial cells and smooth muscle cells can also synthesise tnf\u03b1 . tnf\u03b1 is synthesised as a prohormone and following processing the mature 17 . 5 kda species can be observed . purified tnf\u03b1 has been observed as dimers , trimers and pentamers with the trimeric form postulated to be the active form in vivo . three receptors have been identified for tnf\u03b1 . a soluble receptor seems to function as a tnf\u03b1 inhibitor ( 12 ) while two membrane bound forms have been identified with molecular sizes of 60 and 80 kda respectively . local tnf\u03b1 production at inflammatory sites can be induced with endotoxin and the glucocorticoid dexamethasone inhibits cytokine production ( 13 ). tnf\u03b1 production results in the stimulation of many cell types . significant anti - viral effects could be observed in tnf\u03b1 treated cell lines ( 14 ) and the ifns synergise with tnf\u03b1 enhancing this effect . endothelial cells are stimulated to produce procoagulant activity , expression of adhesion molecules , il - 1 , hematopoitic growth factors , platelet activating factor ( paf ) and arachidonic acid metabolites . tnf\u03b1 stimulates neutrophil adherence , phagocytosis , degranulation ( 15 ), reactive oxygen intermediate production and may influence cellular migration . leucocyte synthesis of gm - csf , tgf\u03b2 , il - 1 , il - 6 , pge 2 and tnf\u03b1 itself can all be stimulated upon tnf\u03b1 administration ( 16 , 17 ). programmed cell death ( apoptosis ) can be delayed in monocytes ( 18 ) while effects on fibroblasts include the promotion of chemotaxis and il - 6 , pge 2 and collagenase synthesis . while local tnf\u03b1 production promotes wound healing and immune responses , the dis - regulated systemic release of tnf\u03b1 can be severely toxic with effects such as cachexia , fever and acute phase protein production being observed ( 19 ). the invention will be more clearly understood from the following examples . characterisation of bacteria isolated from resected and washed human gastrointestinal tract . demonstration of probiotic traits . appendices and sections of the large and small intestine of the human gastrointestinal tract ( g . i . t .) obtained during reconstructive surgery , were screened for probiotic bacterial strains . all samples were stored immediately after surgery at \u2212 80 \u00b0 c . in sterile containers . frozen tissues were thawed , weighed and placed in cysteinated ( 0 . 05 %) one quarter strength ringers &# 39 ; solution . the sample was gently shaken to remove loosely adhering microorganisms ( termed \u2014 wash \u2018 w \u2019). following transfer to a second volume of ringer &# 39 ; s solution , the sample was vortexed for 7 mins to remove tightly adhering bacteria ( termed \u2014 sample \u2018 s \u2019). in order to isolate tissue embedded bacteria , samples 356 , 176 and a were also homogenized in a braun blender ( termed \u2014 homogenate \u2018 h \u2019). the solutions were serially diluted and spread - plated ( 100 \u03bcl ) on the following agar media : rcm ( reinforced clostridia media ) and rcm adjusted to ph 5 . 5 using acetic acid ; tpy ( trypticase , peptone and yeast extract ); mrs ( demann , rogosa and sharpe ); rog ( acetate medium ( sl ) of rogosa ); lla ( liver - lactose agar of lapiere ); bhi ( brain heart infusion agar ); lbs ( lactobacillus selective agar ) and tsaye ( tryptone soya sugar supplemented with 0 . 6 % yeast extract ). tpy and mrs supplemented with propionic acid was also used . all agar media was supplied by oxoid chemicals with the exception of tpy agar . plates were incubated in anaerobic jars ( bbl , oxoid ) using co 2 generating kits ( anaerocult a , merck ) for 2 - 5 days at 37 \u00b0 c . gram positive , catalase negative rod - shaped or bifurcated / pleomorphic bacteria isolates were streaked for purity on to complex non - selective media ( mrs and tpy ). isolates were routinely cultivated in mrs or tpy medium unless otherwise stated at 37 \u00b0 c . under anaerobic conditions . presumptive lactobacillus were stocked in 40 % glycerol and stored at \u2212 20 \u00b0 c . and \u2212 80 \u00b0 c . seven tissue sections taken from the g . i . t . were screened for the presence of strains belonging to the lactobacillus genera . there was some variation between tissue samples . table 1 below shows the bacterial count of the tissue samples expressed as colony forming units per gram ( cfu / ml ) of tissue . ( nd = not determined ) samples a ( ileum ) and 316 ( appendix ) had the lowest counts with approximately 10 2 cells isolated per gram of tissue . in comparison , greater 10 3 cfu / g tissue were recovered from the other samples . similar numbers of bacteria were isolated during the \u2018 wash \u2019 and \u2018 sample \u2019 steps with slightly higher counts in the \u2018 sample \u2019 solutions of 433 ( ileal - caecal ). metabolism of the carbohydrate glucose and the subsequent organic acid end - products were examined using an lkb bromma , aminex hpx - 87h high performance liquid chromatography column . the column was maintained at 60 \u00b0 c . with a flow rate of 0 . 6 ml / min ( constant pressure ). the hplc buffer used was 0 . 01 n h 2 so 4 . prior to analysis , the column was calibrated using 10 mm citrate , 10 mm glucose , 20 mm lactate and 10 mm acetate as standards . cultures were propagated in modified mrs broth for 1 - 2 days at 37 \u00b0 c . anaerobically . following centrifugation for 10 min at 14 , 000 g , the supernatant was diluted 1 : 5 with hplc buffer and 200 \u03bcl was analysed in the hplc . all supernatants were analysed in duplicate . biochemical and physiological traits of the bacterial isolates were determined to aid identification . nitrate reduction , indole formation and expression of \u03b2 - galactosidase activity were assayed . growth at both 15 \u00b0 c . and 45 \u00b0 c ., growth in the presence of increasing concentrations of nacl up to 5 . 0 % and protease activity on gelatin were determined . growth characteristics of the strains in litmus milk were also assessed . approximately fifteen hundred catalase negative bacterial isolates from different samples were chosen and characterised in terms of their gram reaction , cell size and morphology , growth at 15 \u00b0 c . and 45 \u00b0 c . and fermentation end - products from glucose ( data not shown ). greater than sixty percent of the isolates tested were gram positive , homofermentative cocci ( homo -) arranged either in tetrads , chains or bunches . eighteen percent of the isolates were gram negative rods and heterofermentative coccobacilli ( hetero -). the remaining isolates ( twenty two percent ) were predominantly homofermentative coccobacilli . thirty eight strains were characterised in more detail \u2014 13 isolates from 433 ; 4 from 423 ; 8 from 312 ; 9 from 356 ; 3 from 176 and 1 from 316 . all thirty eight isolates tested negative both for nitrate reduction and production of indole from tryptophan . growth at different temperatures , concentrations of nacl and gelatin hydrolysis are recorded in table 2 below . the api 50chl ( biomerieux sa , france ) system was used to tentatively identify the lactobacillus species by their carbohydrate fermentation profiles . overnight mrs cultures were harvested by centrifugation and resuspended in the suspension medium provided with the kit . api strips were inoculated and analysed ( after 24 and 48 h ) according to the manufacturers &# 39 ; instructions . identity of the lactobacillus sp . was then checked by sds - polyacrylamide gel electrophoresis analysis ( sds - page ) of total cell protein ( bruno pot , university of ghent , belgium , personal communication ). finally , 16s rna analysis and ribotyping were used to confirm strain identity . the api 50chl allowed rapid identification of the lactobacillus isolates . analysis of total cell protein of the lactobacillus sp . ( bruno pot , personal communication ) by sds - page , 16s rna analysis and ribotyping revealed further information on the specific species . table 3 below shows the identification of the 5 lactobacillus strains by four different techniques . the api zym system ( biomerieux , france ) was used for semi - quantitative measurement of constitutive enzymes produced by lactobacillus isolates . bacterial cells from the late logarithmic growth phase were harvested by centrifugation at 14 , 000 g for 10 mins . the pelleted cells were washed and resuspended in 50 mm phosphate buffer , ph 6 . 8 to the same optical density . the strips were inoculated in accordance with the manufacturer &# 39 ; s instructions , incubated for 4 h at 37 \u00b0 c . and colour development recorded . the enzyme activity profiles of the 5 strains ah102 , ah103 , ah105 , ah109 , ah110 are presented in table 4 below . none of the strains exhibited lipase , trypsin , \u03b1 - chymotrypsin , \u03b1 - glucuronidase , \u03b1 - mannosidase or \u03b1 - fucosidase activities . antibiotic sensitivity profiles of the isolates were determined using the \u2018 disc susceptibility \u2019 assay . cultures were grown up in the appropriate broth medium for 24 - 48 h spread - plated ( 100 \u03bcl ) onto agar media and discs containing known concentrations of the antibiotics were placed onto the agar . strains were examined for antibiotic sensitivity after 1 - 2 days incubation at 37 \u00b0 c . under anaerobic conditions . strains were considered sensitive if zones of inhibition of 1 mm or greater were seen . antibiotics of human clinical importance were used to ascertain the sensitivity profiles of each of the 5 lactobacillus strains . each of the lactobacilli tested was sensitive to ampicillin , amoxacillin , ceftaxime , ceftriaxone , ciprofloxacin , cephradine , rifampicin and chloramphenicol . the antibiotic sensitivities ( ug / ml ) of lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 are given in table 5 below . human gastric juice was obtained from healthy subjects by aspiration through a nasogastric tube ( mercy hospital , cork , ireland ). it was immediately centrifuged at 13 , 000 g for 30 min to remove all solid particles , sterilised through 0 . 45 \u03bcm and 0 . 2 \u03bcm filters and divided into 40 ml aliquots which were stored at 4 \u00b0 c . and \u2212 20 \u00b0 c . the ph and pepsin activity of the samples were measured prior to experimental use . pepsin activity was measured using the quantitative haemoglobulin assay . briefly , aliquots of gastric juice ( 1 ml ) were added to 5 ml of substrate ( 0 . 7 m urea , 0 . 4 % ( w / v ) bovine haemoglobulin ( sigma chemical co ., 0 . 25 m kcl - hcl buffer , ph 2 . 0 ) and incubated at 25 \u00b0 c . samples were removed at 0 , 2 , 4 , 6 , 8 , 10 , 20 and 30 min intervals . reactions were terminated by the addition of 5 % trichloracetic acid ( tca ) and allowed to stand for 30 min without agitation . assay mixtures were then filtered ( whatman , no . 113 ), centrifuged at 14 , 000 g for 15 min and absorbance at 280 nm was measured . one unit of pepsin enzyme activity was defined as the amount of enzyme required to cause an increase of 0 . 001 units of a 280 nm per minute at ph 2 . 0 measured as tca - soluble products using haemoglobulin as substrate . to determine whether growth of the lactobacillus strains occurred at low ph values equivalent to those found in the stomach , overnight cultures were inoculated ( 1 %) into fresh mrs broth adjusted to ph4 . 0 , 3 . 0 , 2 . 0 and 1 . 0 using 1n hcl . at regular intervals aliquots ( 1 . 5 ml ) were removed , optical density at 600 nm ( od600 ) was measured and colony forming units per ml ( cfu / ml ) calculated using the plate count method . growth was monitored over a 24 - 48 h period . survival of the strains at low ph in vitro was investigated using two assays : ( a ) cells were harvested from fresh overnight cultures , washed twice in phosphate buffer ( ph 6 . 5 ) and resuspended in mrs broth adjusted to ph 3 . 5 , 3 . 0 , 2 . 5 , and 2 . 0 ( with 1n hcl ) to a final concentration of approximately 10 8 cfu / ml for the lactobacilli . cells were incubated at 37 \u00b0 c . and survival measured at intervals of 5 , 30 , 60 and 120 min using the plate count method . ( b ) the lactobacillus strains were propagated in buffered mrs broth ( ph 6 . 0 ) daily for a 5 day period . the cells were harvested , washed and resuspended in ph adjusted mrs broth and survival measured over a 2 h period using the plate count method . to determine the ability of the lactobacilli to survive passage through the stomach , an ex - vivo study was performed using human gastric juice . cells from fresh overnight cultures were harvested , washed twice in buffer ( ph 6 . 5 ) and resuspended in human gastric juice to a final concentration of 10 6 - 10 8 cfu / ml , depending on the strain . survival was monitored over a 30 - 60 min incubation period at 37 \u00b0 c . the experiment was performed using gastric juice at ph \u02dc 1 . 2 ( unadjusted ) and ph 2 . 0 and 2 . 5 . each of the lactobacillus strains tested grew normally at ph 6 . 8 and ph 4 . 5 reaching stationary phase after 8 h with a doubling time of 80 - 100 min . at ph 3 . 5 growth was restricted with doubling times increasing to 6 - 8 h . no growth was observed at ph 2 . 5 or lower , therefore , survival of the strains at low ph was examined . each of the strains was generally resistant to ph values 3 . 5 , 3 . 0 , and 2 . 5 , with lactobacillus salivarius ah102 and ah105 also exhibiting resistance at ph 2 . 0 ( data not shown ). to determine the ability of the lactobacillus strains to survive conditions encountered in the human stomach , viability of each of the 5 strains was tested in human gastric juice at ph 1 . 2 and ph 2 . 5 , as shown in table 6 below . the survival is expressed at log 10 cfu / ml ( nd = not determined ). fresh cultures were streaked onto mrs agar plates supplemented with bovine bile ( b - 8381 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ) and porcine bile ( b - 8631 , sigma chemical co . ltd ., poole ) at concentrations of 0 . 3 , 0 . 5 , 1 . 0 , 1 . 5 , 5 . 0 and 7 . 5 % ( w / v ). plates were incubated at 37 \u00b0 c . under anaerobic conditions and growth was recorded after 24 - 48 h . bile samples , isolated from several human gall - bladders , were stored at \u2212 80 \u00b0 c . before use . for experimental work , bile samples were thawed , pooled and sterilised at 80 \u00b0 c . for 10 min . bile acid composition of human bile was determined using reverse - phase high performance liquid chromatography ( hplc ) in combination with a pulsed amperometric detector according to the method of dekker et al . ( 20 ). human bile was added to mrs / tpy agar medium at a concentration of 0 . 3 % ( v / v ). freshly streaked cultures were examined for growth after 24 and 48 h . human gall - bladder bile possesses a bile acid concentration of 50 - 100 mm and dilution in the small intestine lowers this concentration to 5 - 10 mm . furthermore , under physiological conditions , bile acids are found as sodium salts . therefore , cultures were screened for growth on mrs agar plates containing the sodium salt of each of the following bile acids ( sigma chemical co . ltd ., poole ): ( a ) conjugated form : taurocholic acid ( tca ); glycocholic acid ( gca ); taurodeoxycholic acid ( tdca ); glycodeoxycholic acid ( gdca ); taurochenodeoxycholic acid ( tcdca ) and glycochenodeoxycholic acid ( gcdca ); ( b ) deconjugated form : lithocholic acid ( lca ); chenodeoxycholic acid ( cdca ); deoxycholic acid ( dca ) and cholic acid ( ca ). for each bile acid concentrations of 1 , 3 and 5 mm were used . growth was recorded after 24 and 48 h anaerobic incubation . both a qualitative ( agar plate ) and a quantitative ( hplc ) assay were used to determine deconjugation activity . plate assay : all the cultures were streaked on mrs agar plates supplemented with ( a ) 0 . 3 % ( w / v ) porcine bile , ( b ) 3 mm tdca or ( c ) 3 mm gdca . deconjugation was observed as an opaque precipitate surrounding the colonies . high performance liquid chromatography ( hplc ): analysis of in vitro deconjugation of human bile was performed using hplc . briefly , overnight cultures were inoculated ( 5 %) into mrs broth supplemented with 0 . 3 % ( v / v ) human bile and were incubated anaerobically at 37 \u00b0 c . at various time intervals over a 24 h period , samples ( 1 ml ) were removed and centrifuged at 14 , 000 rpm for 10 min . undiluted cell - free supernatant ( 30 \u03bcl ) was then analysed by hplc . [ 0100 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were capable of growth ( bile acid resistance ) on three sources of bile used . it was observed that resistance to bovine bile was much higher than to porcine bile . each of the lactobacillus strains tested was resistant to concentrations up to and including 5 . 0 % bovine bile ( data not shown ). porcine bile was more inhibitory as shown in table 7 below . regardless of the bile resistance profiles in the presence of both bovine and porcine bile , each of the lactobacillus salivarius strains grew to confluence at the physiological concentration of 0 . 3 % ( v / v ) human bile ( data not shown ). each of the lactobacillus strains , when analysed specifically for its resistance to individual bile acids , grew well in the presence of taurine conjugated bile acids . isolates from each of lactobacillus strain grew to confluence on agar medium containing up to and including 5 mm of taurine conjugates tca , tdca and tcdca . of the glycine conjugates tested , gcdca was the most inhibitory . gdca was less inhibitory and gca was the least inhibitory of the three glycine conjugates . each of the lactobacillus strains grew on agar medium supplemented with 5 mm gca . this is shown in table 8 below . growth in the presence of deconjugated bile acids was also tested . each lactobacillus strain was resistant to concentrations of 5 mm lca . growth in the presence of ca was also tested . as shown in table 9 below , three of the 5 strains , ah102 , ah105 and ah109 grew in the presence of 1 mm ca . none of the strains grew in the presence of 1 mm cdca . ( data not shown ). antimicrobial activity was detected using the deferred method ( 21 ). indicators used in the initial screening were l . innocua , l . fermentum kld , p . flourescens and e . coli v157 . briefly , the lactobacilli ( mrs ) were incubated for 12 - 16 h and 36 - 48 h , respectively . ten - fold serial dilutions were spread - plated ( 100 \u03bcl ) onto mrs / tpy agar medium . after overnight incubation , plates with distinct colonies were overlayed with the indicator bacterium . the indicator lawn was prepared by inoculating a molten overlay with 2 % ( v / v ) of an overnight indicator culture which was poured over the surface of the inoculated mrs plates . the plates were re - incubated overnight under conditions suitable for growth of the indicator bacterium . indicator cultures with inhibition zones greater than 1 mm in radius were considered sensitive to the test bacterium . inhibition due to bacteriophage activity was excluded by flipping the inoculated mrs / tpy agar plates upside down and overlaying with the indicator . bacteriophage cannot diffuse through agar . [ 0108 ] lactobacillus salivarius ah102 , ah103 , ah105 , ah109 and ah110 were screened for inhibitory activity using ls . innocua , l . fermentum kld , p . fluorescens and e . coli as indicator microorganisms . when the test strains were inoculated on unbuffered mrs , inhibition of the four indicators was observed . zones ranging in size from 1 mm to 5 mm were measured . inhibition of ls . innocua by each of the lactobacilli produced the largest zones . the adhesion of the probiotic strains was carried out using a modified version of a previously described method ( 22 ). the monolayers of ht - 29 and caco - 2 cells were prepared on sterile 22 mm 2 glass coverslips , which were placed in corning tissue culture dishes , at a concentration of 4 \u00d7 10 4 cells / ml . cells were fed fresh medium every 2 days . after \u02dc 10 days , and differentiation of the monolayer had occurred , the monolayers were washed twice with phosphate buffered saline ( pbs ). antibiotic - free dmem ( 2 ml ) and 2 ml of \u02dc 18 h lb . suspension containing \u02dc 10 9 cfu / ml were added to each dish and cells were incubated for 2 h at 37 \u00b0 c . in a humidified atmosphere containing 5 % co 2 . after incubation , the monolayers were washed 5 times with pbs , fixed in methanol ( bdh laboratory supplies , poole , uk ) for 3 min , gram stained ( gram stain set , merck ) and examined microscopically under oil immersion . for each glass coverslip monolayer the number of adherent bacteria per 20 epithelial cells was counted in 10 microscopic fields . the mean and standard error of adherent bacteria per 20 epithelial cells was calculated . each adhesion assay was carried out in duplicate . in a second method , after washing 5 times in pbs , adhering bacteria were removed by vortexing the monolayers rigorously in cold sterile h 2 o . bacterial cells were enumerated by serial dilution in quarter strength ringer &# 39 ; s solution ( oxoid ) and incubation on mrs ( lactobacilli ). each of the 5 lactobacillus strains , ah102 , ah103 , ah105 , ah109 and ah110 adhered to gastrointestinal epithelial cells ( fig1 ). these probiotic strains would be suitable as vaccine / drug delivery vehicles as they adhere to the gastrointestinal epithelium and therefore interact with the relevant host tissue . determination of the effect of each of the lactobacillus strains on pbmc cytokine production . peripheral blood mononuclear cells were isolated from healthy donors ( n = 19 ) by density gradient centrifugation . pbmcs were stimulated with the probiotic bacterial strains for a 72 hour period at 37 \u00b0 c . at this time culture supernatants were collected , centrifuged , aliquoted and stored at \u2212 70 \u00b0 c . until being assessed for il - 8 , il - 10 , il - 12 and ifn\u03b3 levels using elisas ( boehringer mannheim ). ah102 , ah103 and ah105 stimulated production of ifn\u03b3 from pbmcs ( fig2 ). ah102 , ah103 , ah109 and ah110 co - incubation did not significantly alter il - 10 levels ( fig3 ). stimulation with ah105 significantly reduced secretion of il - 10 by pbmcs . ah102 , ah105 , ah109 and ah110 co - incubation significantly upregulated il - 12 production by pbmcs ( fig4 ). ah103 had no significant effect on il - 12 production . none of the 5 lactobacillus strains stimulated il - 8 production in vitro , from pbmcs isolated from healthy donors . indeed , in each case , il - 8 levels were reduced ( fig5 ). determination of cytokine levels in an epithelial / pbmc co - culture model following incubation with ah103 and ah110 . the appropriate in vitro model with physiological relevance to the intestinal tract is a culture system incorporating epithelial cells , t cells , b cells , monocytes and the bacterial strains . to this end , human caco - 2 epithelial cells were seeded at 5 \u00d7 10 5 cells / ml on the apical surface of 25 mm transwell inserts with a pore size of 3 \u25a1 m ( costar ). these cells were cultured for four weeks in rpmi 1640 , supplemented with 10 % foetal calf serum , glutamine , penicillin and streptomycin , at 37 \u00b0 c . in a 5 % co 2 environment . culture media was changed every 3 days . when the epithelial cells were fully differentiated , human peripheral blood mononuclear cells ( pbmcs ) were isolated by density gradient centrifugation . 1 \u00d7 10 6 washed pbmcs was incubated basolaterally to the epithelial cells and cultured with 1 \u00d7 10 7 probiotic bacteria . controls contained media alone . no direct cell - cell contact between pbmcs and epithelial cells was possible in this model system and cellular communication was mediated solely by soluble factors . following 72 hours of incubation with ah103 or ah110 , cell culture supernatants were removed , aliquoted and stored at \u2212 70 \u00b0 c . tnf\u03b1 and il - 8 extracellular cytokine levels were measured using standard elisa kits ( r & amp ; d systems ). tnf\u03b1 levels and il - 8 levels were measured , in duplicate , using pbmcs from 3 healthy volunteers . following incubation of epithelial cell - pbmc co - cultures with probiotic bacteria , tnf\u03b1 and il - 8 cytokine levels were examined by elisas ( fig6 ). ah103 significantly reduced the level of il - 8 released by these cells . ah110 reduced the levels of tnf\u03b1 and il - 8 released by these cells . the human immune system plays a significant role in the aetiology and pathology of a vast range of human diseases . hyper and hypo - immune responsiveness results in , or is a component of , the majority of disease states . one family of biological entities , termed cytokines , are particularly important to the control of immune processes . pertubances of these delicate cytokine networks are being increasingly associated with many diseases . these diseases include but are not limited to inflammatory disorders , immunodeficiency , inflammatory bowel disease , irritable bowel syndrome , cancer ( particularly those of the gastrointestinal and immune systems ), diarrhoeal disease , antibiotic associated diarrhoea , paediatric diarrhoea , appendicitis , autoimmune disorders , multiple sclerosis , alzheimer &# 39 ; s disease , rheumatoid arthritis , coeliac disease , diabetes mellitus , organ transplantation , bacterial infections , viral infections , fungal infections , periodontal disease , urogenital disease , sexually transmitted disease , hiv infection , hiv replication , hiv associated diarrhoea , surgical associated trauma , surgical - induced metastatic disease , sepsis , weight loss , anorexia , fever control , cachexia , wound healing , ulcers , gut barrier function , allergy , asthma , respiratory disorders , circulatory disorders , coronary heart disease , anaemia , disorders of the blood coagulation system , renal disease , disorders of the central nervous system , hepatic disease , ischaemia , nutritional disorders , osteoporosis , endocrine disorders , epidermal disorders , psoriasis and acne vulgaris . the effects on cytokine production are specific for each of the probiotic strains examined . thus specific probiotic strains may be selected for normalising an exclusive cytokine imbalance particular for a specific disease type . customisation of disease specific therapies can be accomplished using a selection of the probiotic strains listed above . the enteric flora is important to the development and proper function of the intestinal immune system . in the absence of an enteric flora , the intestinal immune system is underdeveloped , as demonstrated in germ free animal models , and certain functional parameters are diminished , such as macrophage phagocytic ability and immunoglobulin production ( 23 ). the importance of the gut flora in stimulating nondamaging immune responses is becoming more evident . the increase in incidence and severity of allergies in the western world has been linked with an increase in hygiene and sanitation , concomitant with a decrease in the number and range of infectious challenges encountered by the host . this lack of immune stimulation may allow the host to react to non - pathogenic , but antigenic , agents resulting in allergy or autoimmunity . deliberate consumption of a series of non - pathogenic immunomodulatory bacteria would provide the host with the necessary and appropriate educational stimuli for proper development and control of immune function . inflammation is the term used to describe the local accumulation of fluid , plasma proteins and white blood cells at a site that has sustained physical damage , infection or where there is an ongoing immune response . control of the inflammatory response is exerted on a number of levels ( 24 ). the controlling factors include cytokines , hormones ( e . g . hydrocortisone ), prostaglandins , reactive intermediates and leukotrienes . cytokines are low molecular weight biologically active proteins that are involved in the generation and control of immunological and inflammatory responses , while also regulating development , tissue repair and haematopoiesis . they provide a means of communication between leukocytes themselves and also with other cell types . most cytokines are pleiotrophic and express multiple biologically overlapping activities . cytokine cascades and networks control the inflammatory response rather than the action of a particular cytokine on a particular cell type ( 25 ). waning of the inflammatory response results in lower concentrations of the appropriate activating signals and other inflammatory mediators leading to the cessation of the inflammatory response . tnf\u03b1 is a pivotal proinflammatory cytokine as it initiates a cascade of cytokines and biological effects resulting in the inflammatory state . therefore , agents which inhibit tnf\u03b1 are currently being used for the treatment of inflammatory diseases , e . g . infliximab . pro - inflammatory cytokines are thought to play a major role in the pathogenesis of many inflammatory diseases , including inflammatory bowel disease ( ibd ). current therapies for treating ibd are aimed at reducing the levels of these pro - inflammatory cytokines , including il - 8 and tnf\u03b1 . such therapies may also play a significant role in the treatment of systemic inflammatory diseases such as rheumatoid arthritis . irritable bowel syndrome ( ibs ) is a common gastrointestinal disorder , affecting up to 15 - 20 % of the population at some stage during their life . the most frequent symptoms include abdominal pain , bowel habit disturbance , manifested by diarrhoea or constipation , flatulence , and abdominal distension . there are no simple tests to confirm diagnosis , and if no other organic disorders can be found for these symptoms , the diagnosis is usually ibs . patients suffering from ibs represent as many as 25 - 50 % of patients seen by gastroenterologists . many factors are thought to be involved in onset of symptoms including e . g . bout of gastroenteritis , abdominal or pelvic surgery , disturbances in the intestinal bacterial flora , perhaps due to antibiotic intake , and emotional stress . compared with the general population , ibs sufferers may have a significantly reduced quality of life , are more likely to be absent from work , and use more healthcare resources . there are no effective medical treatments and to date , recommended therapies have included antispasmodic agents , anti - diarrhoeal agents , dietary fibre supplements , drugs that modify the threshold of colonic visceral perception , analgesics and anti - depressants . while each of the strains of the invention have unique properties with regard to cytokine modulation and microbial antagonism profiles , it should be expected that specific strains can be chosen for use in specific disease states based on these properties . it also should be anticipated that combinations of strains from this panel with appropriate cytokine modulating properties and anti - microbial properties will enhance therapeutic efficacy . the strains of the present invention may have potential application in the treatment of a range of inflammatory diseases , particularly if used in combination with other anti - inflammatory therapies , such as non - steroid anti - inflammatory drugs ( nsaids ) or infliximab . the production of multifunctional cytokines across a wide spectrum of tumour types suggests that significant inflammatory responses are ongoing in patients with cancer . it is currently unclear what protective effect this response has against the growth and development of tumour cells in vivo . however , these inflammatory responses could adversely affect the tumour - bearing host . complex cytokine interactions are involved in the regulation of cytokine production and cell proliferation within tumour and normal tissues ( 26 , 27 ). it has long been recognized that weight loss ( cachexia ) is the single most common cause of death in patients with cancer and initial malnutrition indicates a poor prognosis . for a tumour to grow and spread it must induce the formation of new blood vessels and degrade the extracellular matrix . the inflammatory response may have significant roles to play in the above mechanisms , thus contributing to the decline of the host and progression of the tumour . due to the anti - inflammatory properties of lactobacillus salivarius these bacterial strains they may reduce the rate of malignant cell transformation . furthermore , intestinal bacteria can produce , from dietary compounds , substances with genotoxic , carcinogenic and tumour - promoting activity and gut bacteria can activate pro - carcinogens to dna reactive agents ( 28 ). in general , species of lactobacillus have low activities of xenobiotic metabolizing enzymes compared to other populations within the gut such as bacteroides , eubacteria and clostridia . therefore , increasing the number of lactobacillus bacteria in the gut could beneficially modify the levels of these enzymes . the majority of pathogenic organisms gain entry via mucosal surfaces . efficient vaccination of these sites protects against invasion by a particular infectious agent . oral vaccination strategies have concentrated , to date , on the use of attenuated live pathogenic organisms or purified encapsulated antigens ( 29 ). probiotic bacteria , engineered to produce antigens from an infectious agent , in vivo , may provide an attractive alternative as these bacteria are considered to be safe for human consumption ( gras status ). murine studies have demonstrated that consumption of probiotic bacteria expressing foreign antigens can elicit protective immune responses . the gene encoding tetanus toxin fragment c ( ttfc ) was expressed in lactococcus lactis and mice were immunized via the oral route . this system was able to induce antibody titers significantly high enough to protect the mice from lethal toxin challenge . in addition to antigen presentation , live bacterial vectors can produce bioactive compounds , such as immunostimulatory cytokines , in vivo . l . lactis secreting bioactive human il - 2 or il - 6 and ttfc induced 10 - 15 fold higher serum igg titres in mice immunized intranasally ( 30 ). however , with this particular bacterial strain , the total iga level was not increased by coexpression with these cytokines . other bacterial strains , such as streptococcus gordonii , are also being examined for their usefulness as mucosal vaccines . recombinant s . gordonii colonizing the murine oral and vaginal cavities induced both mucosal and systemic antibody responses to antigens expressed by this bacterial ( 31 ). thus oral immunization using probiotic bacteria as vectors would not only protect the host from infection , but may replace the immunological stimuli that the pathogen would normally elicit thus contributing to the immunological education of the host . the introduction of probiotic organisms is accomplished by the ingestion of the micro - organism in a suitable carrier . it would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel . the addition of one or more oligosaccharides , polysaccharides , or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract . prebiotics refers to any non - viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value , e . g . bifidobacteria , lactobacilli . types of prebiotics may include those that contain fructose , xylose , soya , galactose , glucose and mannose . the combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit , and is termed synbiotic . it will be appreciated that the probiotic strains may be administered prophylactically or as a method of treatment either on its own or with other probiotic and / or prebiotic materials as described above . in addition , the bacteria may be used as part of a prophylactic or treatment regime using other active materials such as those used for treating inflammation or other disorders especially those with an immunological involvement . such combinations may be administered in a single formulation or as separate formulations administered at the same or different times and using the same or different routes of administration . the invention is not limited to the embodiments herein before described which may be varied in detail . 1 . mccracken v . j . and gaskins h . r . probiotics and the immune system . in : probiotics a critical review , tannock , g w ( ed ), horizon scientific press , uk . 1999 , p . 85 - 113 . 2 . savage d . c . interaction between the host and its microbes . in : microbial ecology of the gut , clark and bauchop ( eds ), academic press , london . 1977 , p . 277 - 310 . 3 . kagnoff m . f . immunology of the intestinal tract . gastroenterol . 1993 ; 105 ( 5 ): 1275 - 80 . 4 . lamm m . e . interaction of antigens and antibodies at mucosal surfaces . ann . rev . microbiol . 1997 ; 51 : 311 - 40 . 5 . raychaudhuri s ., rock k l . fully mobilizing host defense : building better vaccines . nat biotechnol ., 1998 ; 16 : 1025 - 31 . 6 . stalimach a ., strober w , macdonald t t , lochs h , zeitz m . induction and modulation of gastrointestinal inflammation . immunol . today , 1998 ; 19 ( 10 ): 438 - 41 . 7 . de waal malefyt r , haanen j , spits h , roncarolo m g , te velde a , figdor c , johnson k , kastelein r , yssel h , de vries j e . interleukin 10 ( il - 10 ) and viral il - 10 strongly reduce antigen - specific human t cell proliferation by diminishing the antigen - presenting capacity of monocytes via downregulation of class ii major histocompatibility complex expression . j exp med oct . 1 , 1991 ; 174 ( 4 ): 915 - 24 . 8 . schmitt e , rude e , germann t . the immunostimulatory function of il - 12 in t - helper cell development and its regulation by tgf - beta , ifn - gamma and il - 4 . chem immunol 1997 ; 68 : 70 - 85 . 9 . leonard j p , waldburger k e , schaub r g , smith t , hewson a k , cuzner m l , goldman s j . regulation of the inflammatory response in animal models of multiple sclerosis by interleukin - 12 . crit rev immunol 1997 ; 17 ( 5 - 6 ): 545 - 53 . 10 . donnelly r p , fenton m j , finbloom d s , gerrard t l . differential regulation of il \u2014 production in human monocytes by ifn - gamma and il - 4 . j immunol jul . 15 , 1990 ; 145 ( 2 ): 569 - 75 11 . wahl s m , allen j b , ohura k , chenoweth d e , hand a r , ifn - gamma inhibits inflammatory cell recruitment and the evolution of bacterial ; cell wall - induced arthritis . j immunol jan . 1 , 1991 ; 146 ( 1 ): 95 - 100 . 12 . gatanaga t , hwang c d , kohr w , cappuccini f , lucci j a 3d , jeffes e w , lentz r , tomich j , yamamoto r s , granger g a . purification and characterization of an inhibitor ( soluble tumor necrosis factor receptor ) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients . proc natl acad sci usa november 1990 ; 87 ( 22 ): 8781 - 4 . 13 . kawakami m , ihara i , ihara s , suzuki a , fukui k . a group of bactericidal factors conserved by vertebrates for more than 300 million years . j immunol may 1984 ; 132 ( 5 ): 2578 - 81 . 14 . mestan j , digel w , mittnacht s , hillen h , blohm d , moller a , jacobsen h , kirchner h . antiviral effects of recombinant tumour necrosis factor in vitro . nature oct . 30 ,- nov . 5 , 1986 ; 323 ( 6091 ): 816 - 9 . 15 . ferrante a , nandoskar m , walz a , goh d h , kowanko i c . effects of tumour necrosis factor alpha and interleukin - 1 alpha and beta on human neutrophil migration , respiratory burst and degranulation . int arch allergy appl immunol 1988 ; 86 ( 1 ): 82 - 91 . 16 . bachwich p r , chensue s w , larrick j w , kunkel s l . tumor necrosis factor stimulates interleukin - 1 and prostaglandin e2 production in resting macrophages . biochem biophys res commun apr . 14 , 1986 ; 136 ( 1 ): 94 - 101 . 17 . cicco n a , lindemann a , content j , vandenbussche p , lubbert m , gauss j , mertelsmann r , herrmann f . inducible production of interleukin - 6 by human polymorphonuclear neutrophils : role of granulocyte - macrophage colony - stimulating factor and tumor necrosis factor - alpha . blood may 15 , 1990 ; 75 ( 10 ): 2049 - 52 . 18 . mangan d f , welch g r , wahl s m . lipopolysaccharide , tumor necrosis factor - alpha , and il - 1 beta prevent programmed cell death ( apoptosis ) in human peripheral blood monocytes . j immunol mar . 1 , 1991 ; 146 ( 5 ): 1541 - 6 . 19 . dinarello c a , cannon j g , wolff s m . new concepts on the pathogenesis of fever . rev infect dis january - febuary 1988 ; 10 ( 1 ): 168 - 89 . 20 . dekker , r , van der meer , r , olieman , c . sensitive pulsed amperometric detection of free and conjugated bile acids in combination with gradient reversed - phase hplc . chromatographia 1991 ; 31 ( 11 / 12 ): 549 - 553 . 21 . tagg , j r , dajani , a s , wannamaker , l w . bacteriocins of gram positive bacteria . bacteriol rev . 1976 ; 40 : 722 - 756 . 22 . chauviere , g ., m . h . cocconier , s . kerneis , j . foumiat and a . l . servin . adherence of human lactobacillus acidophilus strains lb to human enterocyte - like caco - 2 cells . j . gen . microbiol 1992 ; 138 : 1689 - 1696 23 . crabbe p . a ., h . bazin , h . eyssen , and j . f . heremans . the normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing iga in the gut . the germ free intestinal tract . into . arch . allergy appl immunol , 1968 ; 34 : 362 - 75 . 24 . henderson b ., poole , s and wilson m . 1998 . in \u201c bacteria - cytokine interactions in health and disease . portland press , 79 - 130 . 25 . arai k i , lee f , miyajima a , miyatake s , arai n , yokota t . cytokines : coordinators of immune and inflammatory responses . annu rev biochem 1990 ; 59 : 783 - 836 . 26 . mcgee d w , bamberg t , vitkus s j , mcghee j r . a synergistic relationship between tnf - alpha , il - 1 beta , and tgf - beta 1 on il - 6 secretion by - the iec - 6 intestinal epithelial cell line . immunology september 1995 ; 86 ( 1 ): 6 - 11 . 27 . wu s , meeker w a , wiener j r , berchuck a , bast r c jr , boyer c m . transfection of ovarian cancer cells with tumour necrosis factor alpha ( tnf - alpha ) antisense mrna abolishes the proliferative response to interleukin - 1 ( il - 1 ) but not tnf - alpha . gynecol oncol april 1994 ; 53 ( 1 ): 59 - 63 . 28 . rowland i . r . toxicology of the colon : role of the intestinal microflora . in : gibson g . r . ( ed ). human colonic bacteria : role in nutrition , physiology and pathology , 1995 , pp 155 - 174 . boca raton crc press . 29 . walker , r . i . new strategies for using mucosal vaccination to achieve more effective immunization . vaccine , 1994 ; 12 : 387 - 400 . 30 . steidler l ., k . robinson , l . chamberlain , k . m scholfield , e . remaut , r . w . f . le page and j . m . wells . mucosal delivery of murine interleukin - 2 ( il - 2 ) and il - 6 by recombinant strains of lactococcus lactis coexpressing antigen and cytokine . infect . immun ., 1998 ; 66 : 3183 - 9 . 31 . medaglini d ., g . pozzi , t . p . king and v . a . fischetti . mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium streptococcus gordonii after oral colonization . proc . natl . acad . sci . usa , 1995 ; 92 : 6868 - 72 ."}
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Is the categorization of this patent accurate?
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a4db778829b2230c015edcd82684f100765a2e5a3311beb1fa6fc30286f5993d
| 0.08252 | 0.416016 | 0.130859 | 0.738281 | 0.261719 | 0.523438 |
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{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "General tagging of new or cross-sectional technology"}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Human Necessities"}
|
Does the category match the content of the patent?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.151367 | 0.038574 | 0.034668 | 0.027954 | 0.038574 | 0.037842 |
null |
{"category": "General tagging of new or cross-sectional technology", "patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein ."}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Performing Operations; Transporting"}
|
Is the categorization of this patent accurate?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.421875 | 0.006683 | 0.820313 | 0.019409 | 0.335938 | 0.120117 |
null |
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "General tagging of new or cross-sectional technology"}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Chemistry; Metallurgy"}
|
Does the category match the content of the patent?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.151367 | 0.046631 | 0.034668 | 0.194336 | 0.040283 | 0.049561 |
null |
{"category": "General tagging of new or cross-sectional technology", "patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein ."}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Textiles; Paper"}
|
Is the patent correctly categorized?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.365234 | 0.002045 | 0.574219 | 0.001282 | 0.386719 | 0.009155 |
null |
{"category": "General tagging of new or cross-sectional technology", "patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein ."}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Fixed Constructions"}
|
Is the categorization of this patent accurate?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.421875 | 0.061035 | 0.828125 | 0.039063 | 0.335938 | 0.185547 |
null |
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "General tagging of new or cross-sectional technology"}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting"}
|
Is the category the most suitable category for the given patent?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.034668 | 0.000085 | 0.013611 | 0.000179 | 0.037842 | 0.002258 |
null |
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "General tagging of new or cross-sectional technology"}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Physics"}
|
Is the patent correctly categorized?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.013611 | 0.002625 | 0.071777 | 0.00885 | 0.115723 | 0.047363 |
null |
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "General tagging of new or cross-sectional technology"}
|
{"patent": "the present invention enables treatment of ischemic events , including cerebral ischemia , and reperfusion injury associated with ischemic events . additionally , the present invention permits the treatment of ischemic events in a manner that avoids or minimizes the adverse effects associated with conventional treatments , such as reperfusion injury . the term &# 34 ; treatment &# 34 ; in its various grammatical forms refers to preventing , alleviating , minimizing or curing maladies or other adverse conditions . it has been discovered that plasmin and plasmin - forming proteins , a category that includes lys - plasminogen , a pre - activated zymogen of plasmin , can be used , in accordance with the present invention , to attenuate or avoid reperfusion injury following an ischemic event . this beneficial effect can be obtained even when reperfusion already has started . lys - plasminogen itself can be employed as a treatment . all forms of lys - plasminogen are considered suitable for use with this invention as long as they retain the ability to affect the benefits described above . also suitable for use pursuant to the present invention are fragments of lys - plasminogen and variants of lys - plasminogen , such as analogs , derivatives , muteins and mimetics of the natural molecule , that retain the ability to affect the benefits described above . fragments of lys - plasminogen refers to portions of the amino acid sequence of the lys - plasminogen polypeptide . these fragments can be generated directly from lys - plasminogen itself by chemical cleavage , by proteolytic enzyme digestion , or by combinations thereof . additionally , such fragments can be created by recombinant techniques employing genomic or cdna cloning methods . furthermore , methods of synthesizing polypeptides directly from amino acid residues also exist . the variants of lys - plasminogen can be produced by these and other methods . site - specific and region - directed mutagenesis techniques can be employed . see current protocols in molecular biology vol . 1 , ch . 8 ( ausubel et al . eds ., j . wiley & amp ; sons 1989 & amp ; supp . 1990 - 93 ); protein engineering ( oxender & amp ; fox eds ., a . liss , inc . 1987 ). in addition , linker - scanning and pcr - mediated techniques can be employed for mutagenesis . see pcr technology ( erlich ed ., stockton press 1989 ); current protocols in molecular biology , vols . 1 & amp ; 2 , supra . non - peptide compounds that mimic the binding and function of a peptide (&# 34 ; mimetics &# 34 ;) can be produced by the approach outlined in saragovi et al ., science 253 : 792 - 95 ( 1991 ). protein sequencing , structure and modeling approaches for use with any of the above techniques are disclosed in protein engineering , loc . cit . and current protocols in molecular biology , vols . 1 & amp ; 2 , supra . once a desired fragment or variant of lys - plasminogen is obtained , techniques described herein can be employed for determining whether the fragment or variant is effective for the above therapies , such as treatment of reperfusion injury and , if so , identifying an appropriate dosage range . the rat stroke model described in the example below is a simple and cost - efficient way of performing this testing in vivo . the present invention also contemplates the use of progenitors of lys - plasminogen , that is , precursors of lys - plasminogen as well as substances that act on a lys - plasminogen precursor to generate lys - plasminogen . illustrative of lys - plasminogen progenitors is glu - plasminogen , which is cleaved by an appropriate protease to generate lys - plasminogen . a substance effecting such a proteolytic cleavage is plasmin , the use of which falls within the scope of this invention as stated above . these rat stroke model described below is also useful for evaluating the effectiveness of lys - plasminogen progenitors . lys - plasminogen can be obtained by proteolytic cleavage of glu - plasminogen to remove amino acid sequences from glu - plasminogen . methods of producing lys - plasminogen are described in greater detail in european application 0 353 218 . see also neuwenhuizen , supra . an example presented below demonstrates a previously unknown effect of lys - plasminogen which implicates its efficacy , and that of the lys - plasminogen variants and progenitors as well as plasmin and plasmin - forming proteins , in the treatment of reperfusion injury . until now , lys - plasminogen was only known to function in fibrinolysis . it was not expected that plasmin or any plasmin - forming protein , such as lys - plasminogen , would be able to overcome the blood - brain barrier , which has been presumed to be necessary to be effective at the site of a cerebral ischemic event . other uses for lys - plasminogen exist as well . lys - plasminogen is helpful in treating subjects after cardiac arrest . lys - plasminogen administration may prevent the ischemic damage to neural cells . lys - plasminogen can also be used in the treatment of total body ischemia ( shock ), ischemia of the bowels and lower extremities and for the preservation of organs for transplant by preventing ischemia . administration methods include those used for clotlysis treatments , typically intravenous routes . the dosage of lys - plasminogen to be employed with this invention should be based on the weight of the subject and administered at a dosage of about 10 to 1000 caseinolytic units (&# 34 ; cu &# 34 ;)/ kg . preferably , the dosage should be about 100 to 600 cu / kg , and more preferably the dosage should be about 500 cu / kg . the lys - plasminogen can be administered during blood reperfusion , which would occur when lys - plasminogen is administered along with conventional clot lysis treatments such as t - pa . additionally , the beneficial effect of the lys - plasminogen can still be obtained when it is administered after reperfusion has already begun . preferably , the lys - plasminogen should be administered before or within about 30 minutes after reperfusion has begun . lys - plasminogen variants and progenitors should be administered in dosages that yield the same effect as the dosage ranges discussed above . a treatment in accordance with the present invention can be effected advantageously via administration of the above - described substances in the form of injectable compositions . a typical composition for such purpose comprises a pharmaceutically acceptable carrier . an exemplary composition in this context is a lys - plasminogen buffer vehicle ( 9 g / l nacl , 1 g / l na 3 citrate \u2022 2h 2 o , 3 g / l l - lysine , 6 g / l nah 2 po 4 \u2022 2h 2 o and 40 , 000 kiu / l aprotonin ). pharmaceutically acceptable carriers in this context include other aqueous solutions , non - toxic excipients , including salts , preservatives , buffers and the like , as described in remington &# 39 ; s pharmaceutical sciences , 15th ed . easton : mack publishing co . pp 1405 - 1412 and 1461 - 1487 ( 1975 ) and in the national formulary xiv ., 14th ed . washington : american pharmaceutical association ( 1975 ), the contents of which are hereby incorporated by reference . examples of non - aqueous solvents are propylene glycol , polyethylene glycol , vegetable oil and injectable organic esters such as ethyloleate . aqueous carriers include water , alcoholic / aqueous solutions , saline solutions , parenteral vehicles such as sodium chloride , ringer &# 39 ; s dextrose , etc . intravenous vehicles include fluid and nutrient replenishers . preservatives include antimicrobials , anti - oxidants , chelating agents and inert gases . the ph and exact concentration of the various components of the binding composition are adjusted according to routine skills in the art . see goodman and gilman &# 39 ; s the pharmacological basis for therapeutics ( 7th ed .). in this experimental series ,- the effects of lys - plasminogen on the sequelae of experimentally induced ischemia in rats was evaluated . two different approaches were employed to assess the neurologic consequences of ischemia . ischemia was induced in rats as described below . first , male sprague - dawley rats ( weight 300 - 400 g ) are anesthetized with 350 mg / kg choral hydrate i . p ., and a catheter was then inserted into the jugular vein . five milliliters of blood was withdrawn through the jugular catheter ( 100 iu heparin in the syringe ) in order to reduce mean arterial blood pressure to 50 mm hg . the prepared carotid arteries are exposed and clamped simultaneously with the blood withdrawal . the clamps are removed after a period of 30 minutes , and the withdrawn blood is reinfused ( reperfusion ). fibrin sealant ( tisseel \u00ae) is applied to the wounds . the animals remain under anesthesia for a total of 24 hours ( 23 . 5 hours after reperfusion ). after regaining consciousness , each animal undergoes one of the following procedures : animals are maintained at constant body temperatures for a total of 24 hours , sacrificed with ether and the brains removed . assessment of brain edema was performed using modifications of methods published for other species . oh & amp ; betz , stroke 22 : 915 - 21 ( 1991 ). moisture content , which is an excellent parameter for assessing ischemia / reperfusion - induced edema of the brain , is determined as follows : both hemispheres are weighed , dried for 17 hours at 200 \u00b0 c ., and reweighed . moisture content is was calculated in percent of total moist weight according to the following formula : ## equ1 ## assessment of neurologic deficits : animals were assessed for neurologic deficits on the first , second and third post - operative days . wauquier et al ., neuropharmacology 28 : 837 - 46 ( 1989 ). state of consciousness , gait , muscle tone , performance on an overhead ladder tilted at 45 \u00b0, and performance on a vertically mounted rotating disk were evaluated on the basis of the scoring system shown in fig1 . a cumulative score for the three days is calculated ( maximum score = 54 ). lys - plasminogen ( immuno ag ) was administered intravenously by means of catheter into either the jugular or tail vein . these administrations were performed in increasing concentrations at various time points . ischemic animals treated with isotonic saline served as positive controls , while animals subjected to a sham operation and treated with isotonic saline served as negative controls . the above - described lys - plasminogen buffer was tested using each of these procedures in separate experiments . a summary of dosage , administration schedule , experimental procedures and results is set forth in fig2 . the results for 500 cu / kg lys - plasminogen ( and the buffer employed as a control ) are shown in fig3 and 4 for edema and fig5 and 6 for neurologic deficits . significance values were based on t - tests for edema and the kruskal - wallis test assuming a chi - square distribution for neurologic deficits . a dose of 500 cu / kg of lys - plasminogen showed a significant protective effect on the sequence of experimentally induced cerebral ischemia in rats . the schedule of administration did not play an essential role . notably , the lys - plasminogen still exerted a protective effect even when it was administered 30 minutes after the beginning of reperfusion . this contrasts with results obtained for the standard therapeutic measure flunarizine , which is a calcium antagonist used in clinical practice . flunarizine ( 0 . 63 mg / kg given intravenously ) was effective when administered in the reperfused blood , but had no effect when administered 30 minutes after reperfusion ( data not shown ). lys - plasminogen ( 500 cu / kg ) was capable of reversing the effects of cerebral ischemia as assessed on the basis of brain edema and neurologic deficits in a rat model of experimental ischemia . the buffer used in the lys - plasminogen preparation had no effect . in contrast to a standard therapeutic measure ( flunarizine ), lys - plasminogen was effective even when administered 30 minutes after reperfusion . it is to be understood that the description , figures and specific examples , while indicating preferred embodiments of the invention are given by way of illustration and are not intended to limit the present invention . various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the discussion and disclosure contained herein .", "category": "Electricity"}
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Does the category match the content of the patent?
| 0.25 |
17e83af3ecafba096672ee64b4db227d0ef1496ab31225ccb5ddcb04d4855951
| 0.151367 | 0.000315 | 0.034668 | 0.001068 | 0.040283 | 0.000607 |
null |
{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"category": "Human Necessities", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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Is the category the most suitable category for the given patent?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.164063 | 0.00383 | 0.037354 | 0.005554 | 0.241211 | 0.027222 |
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{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "Physics"}
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{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "Performing Operations; Transporting"}
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Does the patent belong in this category?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.001068 | 0.011658 | 0.015869 | 0.117676 | 0.064453 | 0.19043 |
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{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"category": "Chemistry; Metallurgy", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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Is the patent correctly categorized?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.222656 | 0.004333 | 0.277344 | 0.003082 | 0.412109 | 0.007355 |
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{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "Textiles; Paper"}
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Is the patent correctly categorized?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.222656 | 0.000008 | 0.277344 | 0.002716 | 0.412109 | 0.003708 |
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{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"category": "Fixed Constructions", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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Is the categorization of this patent accurate?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.119141 | 0.04541 | 0.163086 | 0.558594 | 0.271484 | 0.154297 |
null |
{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "Physics"}
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{"category": "Mechanical Engineering; Lightning; Heating; Weapons; Blasting", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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Does the patent belong in this category?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.001068 | 0.017944 | 0.014954 | 0.002625 | 0.064453 | 0.230469 |
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{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "Electricity"}
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Is the categorization of this patent accurate?
| 0.25 |
d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.119141 | 0.000132 | 0.163086 | 0.024414 | 0.271484 | 0.070801 |
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{"category": "Physics", "patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims ."}
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{"patent": "the present invention provides a system for converting input analog signals such as audio signals into digital signals and subsequently coded into structured data sets for recording in condensed digital form ; and , for reconstructing a digital data set similar to the original digital signal input prior to reconversion to the analog form of signal . in its broadest sense , therefore , the recording of the audio signals into a digital form for subsequent playback is accomplished by the provision of a microcomputer recording system which comprises electronic components for converting an analog audio signal into at least three digital data streams , wherein the first of the digital data streams is a relatively broad band reference signal representative of the amplitude of a pre - selected range of audio frequencies , and the second of said data streams is produced by filtering the analog audio signal to produce at least one data stream channel indicative of a sampled band width of frequencies narrower than the band width represented by such first data stream , and a third reference data stream representative of the sampling frequency of the audio signal ; sampling means for producing a sequential stream of data samples from each of the digital data streams , selection means for selecting a pre - determined portion of the digital data sample produced by the sampling means in each of the data streams ; means for separately storing each of said selected digital data samples produced by the sampling means ; means for comparing the reference signal data stream containing amplitude data with said second data stream containing frequency data to produce frequency spectrogram data representative of the frequency and amplitude of the original audio signal ; means for transforming data samples of the third data stream channel selected from the narrower band width into data representative of a time versus amplitude histogram for each band width ; means for comparing said histogram data with selected waveform parameters and producing and storing addressable data representative of the waveform of the original audio input and means for sequentially assembling and storing the frequency spectrogram data and the amplitude reference data of the first data stream and the addressable waveform data for subsequent playback use . in the preferred embodiment shown in fig1 the input signal is conditioned and amplified in the first stage of the data acquisition module ( dam ). the dam is a multi - channel programmable microprocessor based device that utilizes standard integrated circuits to perform three functions : 1 . to sample at the rate of 42 khz , hold , digitize , and output the broadband ( 20 hz to 20 khz ) audio signal level ( dc voltage ) of amplitude every 0 . 01 second . thus , 100 times every second a digital &# 34 ; word &# 34 ; composed of from 4 to 14 bits is created for assembly as part of a disk record file . 2 . to sample , hold , digitize and output an audio frequency spectrogram every 0 . 01 second from a 128 segment array of logical bandpass filters which sample 128 channels and are arranged logarithmically over the overall band width used . the data set produced by this function may range from null ( no signals on any channel ) to ( n ) [( 7 bit identifier +( 7 bit scaler )+( 2 bit pointer )] where ( n ) is the number of channels with signal content . 3 . to act as a digital storage oscilloscope loader , assembling strings of digitized amplitude versus time data ( histograms ) corresponding to the array of bandpass filters selected in paragraph 2 , above . this assembled data set is produced every 0 . 01 second and is the largest single data structure and contains time continuous listing for every active bandpass filter . the number of &# 34 ; words &# 34 ; in each string is a function of the filter center frequency and requires as many as 4 , 000 samples for a 20 khz channel , or as few as five samples for a 20 hz channel . this data set is not sent to the file assembler as in paragraphs 1 and 2 , above , but is loaded into a random access memory ( ram ) buffer where it is accessible by the waveform analyzer and coder module . the function of the waveform analyzer and coder module ( wac fig1 ) is to be a digital numeric processor array that is programmed to extract characteristic wavcforms from the data set stored in the ram by the dam described above . the waveform data are reduced to tabular form in which one period of each waveform codified is assigned to one wave table which preferably is a digitized x - y coordinate system consisting of 1 , 024 bytes along the x axis and an 8 bit &# 34 ; word &# 34 ; in each byte location to scale the y axis in 256 increments ; 127 above zero and 127 below . a set of wavetables is therefore generated for all active bandpass filter channels every 0 . 10 second . a range of 0 to 128 p . m . s . tables may be generated per cycle ( 0 . 01 second ). the wac utilizes either one of several p . m . s . reductive analytic methods to find waveforms . the first being the fast fourier transform ( fft ) and the second the fast delta hadamard transform ( fdht ). the two methods may be briefly described as follows : the fft is based on the principal that almost any periodic function f ( x ) of period 2 of vibrations can be represented by a trigonometric series of sines and cosines . the full expression in general terms is : ## equ1 ## the algorithm for executing this equation efficiently was first published by rabiner & amp ; gold , 1974 and oppenheim and schafer , 1975 . the fdht is utilized for the analysis of spectral composition of a data set where the spectrum \u03c8 is in the form : ## equ2 ## where fi is the frequency and \u03c8 i is signal intensity . in the present application of this method the digital output of the logical filters from hereinbefore numbered paragraph 2 , is summed at each filter and added to the next output until all frequencies have been sampled . at the last step the total output is : ## equ3 ## then an estimation of the spectrum ( \u03c8 &# 39 ;) can be found by matrix multiplication : ## equ4 ## the algorithm for implementing the fdht was published in 1983 by e . e . fenimore at los alamos national laboratory . b - splines computational algorithms may also be employed to extract characteristic waveforms . ten times every second the latest produced set of waveform tables are sent to the disk record assembler ( dra fig1 ). the disk record assembler ( dra ) is a program module that receives as input the waveform table references ( addresses ) from the wac every 0 . 10 seconds and paragraph 2 ( above ) frequency spectrogram data sets every 0 . 01 seconds directly from the data acquisition module ( dam ) as well as the digital word representing the total broadband signal strength . the waveform tables are kept in a local memory buffer in the dra so that they may be revised or discarded every 0 . 10 second cycle by a subroutine which for convenience will be called waveform catalog maintenance . disk records ( fig4 ) for storage are variable in length but always follow this format : the first 14 bits are the field length statement , the next 7 bits are the frequency filter or channel identifier followed by a 2 bit pointer ( flag ) and its 7 bit scaler , 7 bit waveform table identifier , 7 bit simultaneous waveform table identifier ( repeat if necessary ), 2 bit flag ( signals next filter identifier ), and so forth to the last 14 bit word which is the broadband signal level . the data stream format is shown graphically in fig4 . once a record is prepared for storage it is held in a local memory buffer in the dra for one cycle so it can be compared to the next sequential record . this allows the dra to utilize &# 34 ; tokens &# 34 ;; specific reserved symbols to identify &# 34 ; repeats &# 34 ;, &# 34 ; same excepts &# 34 ; and &# 34 ; nulls &# 34 ; in the current record being assembled to save storage space . the waveform catalog maintenance subroutine is programmed to evaluate incoming updates of waveform tables against the waveform tables previously stored , and among themselves . since there are only 128 channels available for storage of the amplitude histogram output of the dam , the comparison of the waveform output of the wac with the stored waveform data of the dra determines redundancy and duplicates are discarded . the remaining incoming tables are possibly unique or simply improved versions of forms already stored . waveforms that contain new features on existing tables are saved in place of their previous table resident . unique forms are assigned new tables . when an overload occurs due to a &# 34 ; full house &# 34 ; and a unique waveform arrives it is placed in a local buffer for one cycle to determine its repetitiveness . if indeed it does occur in the next 0 . 10 second cycle , space in the waveform catalog is made for it by discarding the waveform most similar to another in the catalog . the algorithms used for these evaluations are based on standard statistical methods for measuring the fit of two curves to one another . in the preferred embodiment of this invention the storage medium is a 5 . 25 &# 34 ; magnetic disk commonly in use for digital magnetic storage and retrieval . these disks have a storage capacity of about 1 megabyte ( 1 million bytes or 8 million bits ) and are anticipated to reach 10 megabytes in the near future . for purposes of illustration , a 5 megabyte disk will be assumed . assembled disk records from the dra are the input for the disk read / write module . in the &# 34 ; write &# 34 ; mode , records in the form of the data stream format previously described , will be written to disk storage as long as there is space available . considering an average record to be 20 bytes of data the disk will contain about 240 , 000 records , each representing 0 . 01 seconds of real time . in addition the entire waveform catalog is written to disk after all space on the disk has been filled except for the 130 kilobytes required for the waveform catalog itself . in the retrieve mode , or playback , the disk read / write module first reads the waveform catalog from the disk into ram . the waveform tables are then accessed by the player module when called within each disk record . each 0 . 01 second disk record is read from the disk serially to preserve its relationship to the real time of the original audio source material . the player module utilized in the present invention will preferably contain digital oscillators to produce the output signal and &# 34 ; smoothing &# 34 ; filters to eliminate the &# 34 ; steps &# 34 ; inherent in digital representations of continuous analog functions . additive synthesis is the principal upon which the player module &# 39 ; s logic is based . briefly summarized , additive synthesis theory states that complex musical signals can be constructed by summing all of the voltage components of the signal of each frequency subset at each instant in time . thus , if the data reduction process preserves all of the original information about voltage versus time in such a way that it can be recombined precisely and in phase in time the output signal will equal the original input signal in each specified frequency or &# 34 ; pitch &# 34 ;. in the preferred embodiment of the invention these conditions of additive synthesis are preserved at a level of perceptual resolution so that what the human ear will hear is indistinguishable from the original for most source material . the player module then directs the oscillators to output at the frequencies specified by the disk records utilizing the waveform reference data to set the timbre of each oscillator and the broadband amplitude reference data sets the voltage levels . synchronized timing is built into the system by definition of the 0 . 01 second cycle time upon which the system is based . a most preferred embodiment of the system will employ very large scale integrated circuit ( vlsis ) technology to reduce logical groupings of circuit to single semiconductor chips , as opposed to the schematic representation shown in fig5 which utilizes many &# 34 ; off the shelf &# 34 ; integrated circuit components . referring now to fig2 the analytic model is graphically depicted . the model has three reference axis dimensions of measurement ; time , amplitude ( dc voltage ), and frequency . the time axis is divided into 0 . 01 second increments . it is important to the understanding of the system of the present invention to realize that the 0 . 01 second interval corresponds to the rate at which incremental acoustic &# 34 ; snapshots &# 34 ; of the audio signal are recorded . this increment was chosen because it is short enough that the human ear physiologically hears a sequence of 0 . 01 second changes in total signal as a continuous integrated whole . the stream of acoustic &# 34 ; snapshots &# 34 ; is directly analogous to the stream of &# 34 ; frames &# 34 ; in a motion picture film . the acoustic &# 34 ; snapshots &# 34 ; themselves contain , in binary form , the total broadband ( 20 to 20 , 000 hz ) amplitude , a frequency spectrogram and waveform table references obtained from the dam ( fig1 ). the illustration in fig2 amplitude histograms , such as ( ah 6 ) shows the waveforms contained in the so - called &# 34 ; amplitude histograms &# 34 ; which are the raw data sets used to write the waveform tables . this will be discussed in greater detail hereinafter . the total broadband amplitude record is the reading , every 0 . 01 seconds , of a continuous digital stream of 14 bit words &# 34 ; written &# 34 ; by the broadband sample , hold and digitizing circuit at the rate of 42 , 000 &# 34 ; words &# 34 ; per second . viewed another way this is like saying that only one word is saved for every 420 created . this series of amplitude readings is utilized from the ram buffer module in the &# 34 ; playing &# 34 ; of the digital oscillators at the output end of the system . every amplitude reading in every frequency channel is scaled to this reference level . referring again to fig2 ; ( bbr ) &# 34 ; broadband reference record &# 34 ; is a 2 dimensional data array in which the first term is the time value within the 0 . 10 second time frame incremented every 0 . 01 seconds ( i . e . 0 , 0 . 01 , 0 . 02 , seconds ). the second term is the binary representation of the dc voltage level or amplitude at each time increment . the voltage level is recorded to the accuracy of a 14 bit word . this allows 16 , 384 discreet values for representation of the dc voltage range which may typically be from 0 . 05 volts to 5 volts i . e . 100 db . the absolute accuracy is thus 4 . 95 divided by 16 , 384 or \u00b1 0 . 0003 vdc . it would be desirable to have this level of accuracy for the vdc measurement recorded in each bandpass filter channel . however , to achieve economy of storage space it is desirable to use as few bits as possible to represent the amplitude of the signal in each channel . to accomplish these contradictory goals the method of relative representation is adopted . each frequency channel amplitude record is a bit word called a scaler value , that allows 128 values , which records each channel &# 39 ; s signal as a proportion of the broadband value . thus a channel with a vdc that is 0 . 250 vdc when the broadband value is 3 . 250 has a proportional value of 0 . 07692 with respect to the broadband signal . on a 7 bit scale this is a &# 34 ; 3 &# 34 ; out of 128 . the second benefit of this approach is the increased speed of computation afforded by the comparative nature of modular arithmetic logic as opposed to the more time consuming logic for accumulating and encoding a 14 bit accurate &# 34 ; word &# 34 ; at each channel , thus utilizing a 7 bit word instead of a 14 bit word is a 50 % savings in storage space . referring now to fig3 the frequency spectrogram fs 10 is similar to the broadband amplitude record except that the amplitude of the voltage in each of 128 discreet narrow bandwidths is &# 34 ; saved &# 34 ; every 0 . 01 seconds . the 128 channels are sample , hold and digitizer circuits that are limited to the bandwidths they can &# 34 ; hear &# 34 ; by preselected digital bandpass filters . the distribution of the channels across the 20 to 20 , 000 hz audio range may be controlled by the user with equalizer type slide switches or may be automatically signal seeking . that is , the logic of the 128 channel array responds to the amplitude of the voltage in each of 128 discreet narrow band widths and &# 34 ; self - centers &# 34 ; around &# 34 ; live &# 34 ; bandwidths . this principal is the same as used in signal seeking radio receivers . as representatively shown in fig2 there can be overlaps between channels such as shown by the shaded triangular regions on the frequency spectrogram axis . a signal in the overlap region indicates to the system logic that the channel array is not &# 34 ; in tune &# 34 ; with the incoming digitized signal and can serve to set a flag value for correction that can be used by the automatic ranging circuit to &# 34 ; step over &# 34 ; to the next acoustic &# 34 ; snapshot &# 34 ; to get a centered channel reading . the amplitude histograms , for example ah 6 in fig2 are created whenever a channel is &# 34 ; live &# 34 ;. these histograms are point by point amplitude versus time binary plots that are generated on a real time continuous basis . they are not 0 . 01 second &# 34 ; snapshots &# 34 ;. the actual length in time required for plotting a histogram will vary with the audio frequency of the channel . it is generally conceded that the higher the frequency , the more data points will be required to &# 34 ; feed &# 34 ; the waveform analyzer and coder . of course , the upper limit in time for this process is 0 . 10 seconds or the synchronization of the entire system would be affected . the purpose of the amplitude histograms is to provide the &# 34 ; raw data &# 34 ; for the fft or fdht routines that operate the wac . in order for the fft to characterize a series of x - y coordinates as a periodic curve function at least 2 complete cycles of the periodic function must be collected . in many cases , due to electronic recording logic circuit delays often referred to as &# 34 ; settling time &# 34 ; disturbances , more than 2 cycles worth of data must be collected for analysis . referring now to fig3 the wave table catalog information is graphically represented in its preferred form for the system . as soon as the waveform analyzer and coder ( fig1 ), has &# 34 ; found &# 34 ; a waveform in an amplitude histogram ( fig2 ah 6 ) the waveform data for one period of the waveform is plotted on an x - y coordinate system as shown graphically in wave table wt 1 , of fig3 . the amplitude of the wave is plotted in the y dimension with 1 , 020 8 bit binary words that allow a precision of 127 steps above and below the x axis . the x axis itself is an arbitrary division of the waveform &# 39 ; s period into 1 , 020 increments . the wave table has four bytes reserved for information about the tables status within the catalog of 128 tables . this is necessary since references to wave tables positions are made in each 0 . 01 second acoustic &# 34 ; snapshot &# 34 ; that may be revised as the recording proceeds and more or better information becomes available . preferable all rewrites of wave table references are accomplished at the end of an entire recording session in one pass through the disk records . referring to fig4 the bit pattern for a typical acoustic &# 34 ; snapshot &# 34 ; is graphically depicted . an average diskette will contain 240 , 000 of these acoustic &# 34 ; snapshots &# 34 ;. the first binary word is 14 bits long and is the binary number that is equal to the total number of bytes that follow in the acoustic &# 34 ; snapshot &# 34 ;. this field length statement is necessary for control of the system data flow on playback . the &# 34 ; player &# 34 ; module must be told by the controlling software how much data to buffer for 0 . 10 second of real time output . the following seven bit word tells the player the first of the frequency identifiers contained in the acoustic &# 34 ; snapshot &# 34 ; followed by its two bit flag for frequency shifting , i . e . whether it is necessary or not , and in which direction . the third seven bit word is a binary number ( from 1 to 128 ) that sets the relative amplitude ( voltage level ) for the previously stated frequency output . the forth seven bit word is a binary number ( from 1 to 128 ) that tells the player where to find the waveform in the waveform table that is to be addressed with the frequency previously stated . the fifth and sixth seven bit words are also waveform table references to be applied to the first frequency statement . in operation , the &# 34 ; player &# 34 ; reads through the acoustic &# 34 ; snapshot &# 34 ; ( disk record ) and then proceeds to &# 34 ; load &# 34 ; a digital oscillator circuit with the values it has located by reference and those it has read directly from the acoustic &# 34 ; snapshot &# 34 ;. for example , in the case of the record shown in fig4 there are four frequencies called for . each of these has a known number of oscillation frequencies , they are the same as the channel bands . these frequencies are assigned to specific digital oscillators . the amount of energy to be used to drive the oscillator is specified by the relationship of the scaler to the broadband reference signal specified by the 14 bit word at the end of the acoustic &# 34 ; snapshot &# 34 ;. the waveform table references are linked to the frequency oscillators in the same order that they appear in the acoustic &# 34 ; snapshot &# 34 ;. each oscillator acquires the characteristic sound represented by the sum of the waveforms applied to it by the player . the number of times a wave table is read per second by the player for an oscillator is a function of the frequency of the oscillator ; i . e . a 440 hz oscillator cycles ( or reads ) a wave table at the rate of 440 times a second . referring to fig5 a typical schematic layout of the components and their interconnections are shown for a preferred embodiment of the present invention . comparing the requirements shown in fig1 for the various functions with the capabilities of various available electronic components , one can practice the present invention by selecting components having the requisite capabilities . for example , the broad band digitizer used in the data acquisition module ( dam ) can be selected from commercially available high speed analog to digital encoders such as are available from hewlett packard , datel , inc ., intel or r . c . electronics . the 128 channel array in the dam can also be obtained from hewlett packard to convert analog to digital with specified pass characteristics for each channel . currently 16 channel components are available so that eight of such components would be required . as indicated in the figures and the description contained herein , components such as the ram should have up to 500k byte capacity ; read only memory ( rom ) 320k bytes and the central processing unit ( cpu ) shown in fig5 should preferably have 16 byte 8 mhz capacity with multiple 80 byte numeric data processor add on capacity . the disk drive unit shown may be replaced by any suitable means of digital read / write storage such as magnetic bubble memory packs , linear magnetic tape drives , laser based disks or fiches . the user control pad may offer tone , gain , range , track select and other additional features or it may be as simple as on / off , record / playback . signal input and output is via conventional rca type jacks . the preferred embodiment of the present invention has been described with particular emphasis on the required functional characteristics of the components in the system logic that has been employed . it should be apparent that a wide variety of components may be applicable for use in the general system described to achieve the same or similar results . for example , different sampling rates , or the like may be employed advantageously with other components without departing from the spirit of the invention described . indeed the recording and playback functions can be integrated or separate and indeed it will be possible that the record format disclosed could be used with a computer or computer communications link , such as a modem to transmit the recorded data to a remote playback facility . additionally , digital information can be broadcast by an rf signal to a remote location for loading a local memory unit with the requisite wave table information and then the digital data set information on the record can be transmitted for playback at the remote location . this can be done with relatively narrow bandwidth transmissions . the audio signal could then be reproduced by the playback unit at a remote location from the transmitted rf digital information . again , this system has the advantage of achieving the high signal to noise ratio outputs which are inherent in digital communication systems . the preferred embodiment of the present invention has been described in terms of the recording of sound and its playback . in addition to using the described system for audio playback , the output may be used for stimulating the auditory nerves in the manner achieved by hearing aids or artificial ears . no software changes would be necessary for achieving this output response . the same concepts of the instant invention can apply equally well to medically related acoustic , eeg , or ekg analog signals . here waveform tables established during a baseline medical exam using these non - invasive diagnostic techniques can be used to digitize and condense the analog signals during stress , post operative or post treatment diagnosis . the medical input could also be via an ultrasound probe and the instant invention could also store ultrasound images and analyze them for density and other sound wave detectable features . the input of the present invention could also be a security listening device . the data streams of the instant invention would thus be indicative of security sound information . the random access memory would provide data for a comparison between potential break - in sound patterns and previously collected sound records . this would eliminate false trips of the alarm system . memory disks could be changed to the use factor of the secured area . for example , a &# 34 ; week - end &# 34 ; disk would have an entirely different reference than a &# 34 ; night - shift &# 34 ; disk . the input device could be vibration detection device acoustically coupled to a piece of machinery such as an electric dynamo , mill , or press in a manufacturing plant , or any other device incorporating bearings which are heavily or cyclically loaded . the analog input contains numerous frequency , amplitude , and waveform information which is indicative of the condition of these bearings . this information can be analyzed by the microcomputer system of the instant invention and used to detect the otherwise subtle changes in these signal parameters to predict impending bearing failure , or the like . fig6 illustrates still another application of the microcomputer system disclosed supra . in this embodiment , an inventory detection and analysis system is disclosed . here , the input to the data acquisition module of fig1 is a hand held rangefinder device 10 . preferably , device 10 further includes a remote bar code reader of the holographic type . device 10 is connected to a microcomputer system 12 ( preferably of the type employing a battery power - pack for complete portability ), incorporating the functional system of fig1 . goods g are arrayed on shelves in the location to be inventoried . shelves also should incorporate bar codes b on at least one end of each shelf space . the goods should be stacked , if more than one deep , from the back of the shelves , leaving partially filled columns exposed for easy detection by device 10 . the bar codes are commodity codes or other item specific designations describing the goods arrayed on the bar coded shelf . alternatively , a key pad could be used to manually enter this information , before scanning each shelf with device 10 . in operation , the portable microcomputer is initialized , and the disc record assembler module and other control codes are entered . the operator would stand in front of the goods g on shelves and if necessary , key in the goods description ( commodity code , stock number , etc .). where a bar code reader is incorporated in device 10 , this step is not necessary . device 10 is aimed at the shelved goods and is scanned along the full width of the shelf . a typical example of the resulting analog signal is shown in fig7 . this signal corresponds to the depth of space along the goods loaded shelf as a function of time as determined by the rangefinder echo . the time period in this case corresponding to the time between detection of the bar codes on the shelf uprights ( where applicable ) or the shelf uprights themselves . this analog contains frequency , amplitude and wave form characteristics which are manipulated , modified , and condensed to form the digital disc record as set forth supra . this digital record can later be sent via conventional modem to a central inventory control location for later display in graphic or tabular form . an example of a non - acoustic output of the data compresser and recorder of the present invention would be its application to seismagraphic data recording , compression , and analysis . the output in this instance would be a &# 34 ; groomed &# 34 ; graph with features over a specified size and minus noise or reverberations beyond a specified order of harmonics . also , any sensor that outputs an analog waveform type of signal can use the instant invention as a data compressor and recorder . examples of these sensors would include pressure transducers , flow meters , photodiodes , microwave receivers ( radar and radio frequency ), photocells , piezo electric devices , charge - coupled devices , and scintillation counters . likewise , digital data that is representative of waveform data can be compressed , according to this invention , by first converting the digital data into analog signals which can then be processed by the system described herein according to the methods disclosed . in the system described the process methodology for sampling , analyzing , coding and recording and then decoding and playback enables the system to achieve up to three hundred times the storage density of previous systems . the scope of the invention is therefore to be limited only by the prior art as applied to the appended claims .", "category": "General tagging of new or cross-sectional technology"}
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Does the patent belong in this category?
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d0eae9f6586589a73c1fcf3e317a1b928429a2a69f8f2d3f4987c182d5fbc475
| 0.259766 | 0.081543 | 0.310547 | 0.863281 | 0.371094 | 0.554688 |
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{"category": "Human Necessities", "patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs ."}
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{"patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs .", "category": "Performing Operations; Transporting"}
|
Is the category the most suitable category for the given patent?
| 0.25 |
1d5133cde40c92eaabe8131cbdf960efd3029fddffc551de233b4ea69b05bd19
| 0.026001 | 0.004913 | 0.023682 | 0.069336 | 0.123535 | 0.175781 |
null |
{"category": "Human Necessities", "patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs ."}
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{"patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs .", "category": "Chemistry; Metallurgy"}
|
Is the category the most suitable category for the given patent?
| 0.25 |
1d5133cde40c92eaabe8131cbdf960efd3029fddffc551de233b4ea69b05bd19
| 0.026001 | 0.000969 | 0.023682 | 0.001984 | 0.123535 | 0.015869 |
null |
{"patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs .", "category": "Human Necessities"}
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{"category": "Textiles; Paper", "patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs ."}
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Does the patent belong in this category?
| 0.25 |
1d5133cde40c92eaabe8131cbdf960efd3029fddffc551de233b4ea69b05bd19
| 0.004211 | 0.243164 | 0.166992 | 0.0065 | 0.108398 | 0.090332 |
null |
{"patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs .", "category": "Human Necessities"}
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{"category": "Fixed Constructions", "patent": "while the support device of the present invention may be used in a range of different vessels , including blood vessels , it has particular application in procedures where an organ or anatomical region is undergoing localized perfusion with a therapeutic , diagnostic or other agent . for simplicity , these agents will be hereinafter referred to as therapeutic agents . however , it is to be understood that the term \u201c therapeutic \u201d is not to be construed as limiting , and that it includes , without limitation , therapeutic , diagnostic , prophylactic and other agents not specifically identified herein , but which would be considered by the relevant skilled addressee to be suitable for perfusion to an organ or anatomical region . perfusion may be total perfusion , where the entire organ is totally or substantially isolated from the systemic flow , or partial perfusion where only a portion of the organ is substantially isolated . localized perfusion of this kind presents advantages by improving efficacy and the time exposure of the therapeutic agent to the relevant cells . it also limits exposure and hence toxicity to non - target cells as described in brief above . however , it is to be understood that the present invention may also be used simply to collect or drain fluid from an organ or region . collected fluid may be removed from the subject and re - circulated into the organ , filtered and / or treated , or discarded . in some organs , it may be difficult to achieve total isolation , so partial isolation and perfusion may be performed , for example to the right or left lobe of the liver . despite partial perfusion being capable of delivering therapeutic agent to merely a part of the organ , significant therapeutic benefit may still be achieved . particular benefit may be achieved where perfusate is collected after perfusing the target organ , so as to prevent subsequent circulation of the therapeutic agent to other regions of the body where toxic effects may be observed , or the therapeutic agent wasted . the benefit may be improved further where collected perfusate is re - circulated into the target organ utilizing any therapeutic agent which remains after a first pass through the target organ . this may be achieved using the approach described in published patent application wo2005 / 082440 , the entire contents of which are herein incorporated by reference . as discussed infra , when fluid is collected from vessels draining from a target organ or region , one or more of these vessels may require cannulation with a collection catheter . when fluid is drained through these collection catheters , the vessels in which they are positioned become susceptible to collapse as the pressure inside decreases . while some vessels may be more susceptible to collapse than others , the support device of the present invention can provide advantages by supporting and stabilizing the vessel and even anchoring the collection catheter in position . the support device of the present invention may facilitate or at least improve the performance of perfusion . in some instances , the advantages of the present invention have been found to be essential to maintaining adequate positioning of collection catheters and flow rates within the vessel during perfusion . the right and left lobes of the liver have been identified as possible target regions and in this context , the support device may be deployed in one of the hepatic veins to support and maintain patency of the vein as fluid ( e . g . perfusate ) is collected from the liver . however , it is to be understood that fluid from many other organs or regions may be accessed in this way . deploying the support device may also protect the vessel wall by maintaining the tip of the catheter substantially centrally of the vessel or at least at a distance from the vessel walls to prevent aspiration or cavitation . deployment of the device may refer to partial or complete deployment . in complete deployment , the entire expandable member is released from the catheter and expanded to its full extent . in partial deployment , part of the expandable member is retained within the catheter and the amount of expansion is limited by the diameter of the catheter opening . partial deployment may be useful where , for example , during deployment it is found that the diameter of the expandable member may exceed the vessel diameter by an unsafe amount and complete deployment is likely to damage the vessel wall . limiting expansion of the device by partial deployment may avoid vessel damage . partial deployment may also stabilize the expandable member by limiting its movement relative to the catheter tip . thus by retaining part of the expandable member within the catheter , torsional , axial and lateral movement of the member , relative to the catheter is prevented or at least minimized by the struts of the expandable member being in abutment with the internal surface of the catheter . alternatively , the expandable member may be modified at the proximal end , for example by incorporating a lead , a link or other means to limit the extent of movement possible between the catheter tip and the expandable member once deployed . as a further positioning aid , markings may be provided at the proximal end of the control stem / shaft , outside the patient &# 39 ; s body . as the device is released into the vessel , the markings may be utilized to indicate the distance of device deployment , past the catheter tip . during collection of fluid from the vessel , low pressures may develop at the collection device tip , particularly where a roller / peristaltic pump or the like is used to draw fluid from the target organ out of the vessel . this may be indicated by pressures in a lumen feeding into the pump as low as , for example , \u2212 190 mmhg , although clearly these pressures are variable depending on the vessel type , health and age of the subject , characteristics of the perfusion circuit and the like . in the absence of the inventive support device , these pressures can cause the vessel to collapse . not only would vessel collapse affect the perfusion procedure , vessel collapse can also cause venous pooling in the organ and irreversible tissue damage . the advantages and benefits of the present invention will be expanded upon in the following detailed description presenting some of the preferred embodiments of the invention , and the specific examples which follow . it is to be understood that the embodiments and examples provided herein are intended to indicate how the present invention may be performed and are not intended to be limiting on the scope of protection sought as is defined in the claims appended hereto . fig1 a shows an example of an expandable member , in its expanded condition , suitable for supporting a vessel . expandable member 104 is provided in the form of an expandable framework and is adapted to be percutaneously deliverable to the blood vessel in a collapsed condition . fig1 b shows the expandable member in a collapsed condition within a catheter 110 , in which ends 105 , 107 have been drawn apart to radially reduce the member . when collapsed within catheter 110 , atraumatic tip 101 may protrude from the catheter to assist in guiding the support device into the vessel prior to deployment . when the expandable member has been guided into the target blood vessel , the catheter 110 is retracted ( or the expandable member is pushed out of the catheter ), deploying the device into the vessel where it expands . fig1 c shows the support device fully deployed from the catheter , with the expandable member in its fully expanded condition . a guidewire or stem 106 extends within the catheter 110 and is used to deliver the device from a point of entry through the peripheral vasculature to the target vessel . atraumatic tip 101 coupled to the expandable member 104 , is adapted to make atraumatic contact with vessel walls during placement of the device by deforming or deflecting off the vessel wall on contact . this can be achieved by incorporating flexibility into the tip so that it deforms upon contact with the vessel wall . alternatively or additionally , the tip may be shaped or curved to avoid trauma . the atraumatic tip may take any one of a number of forms . in the examples illustrated in fig1 to 3 , the atraumatic tip 101 , 201 is j - shaped . however , other shapes are considered to be suitable , including but not limited to those illustrated in fig4 . for example , the atraumatic tip may have a cross section which is enlarged relative to the guidewire radius , and have a smooth surface so as to avoid causing perforation when the tip comes into contact with the vessel wall . one such example is shown in fig4 a where the atraumatic tip 401 is tear - shaped . alternatively , the atraumatic tip may include a portion having a pigtail shaped curve 402 ( fig4 b ), or an angled tip ( not shown ). preferably , the expandable member is formed from a biocompatible superelastic material , or alternatively from a shape memory material or a material which exhibits both of these properties , being capable of recovery after deformation for delivery in a collapsed or compressed state within a catheter . devices manufactured using these materials can be collapsed for percutaneous delivery to a deployment site and then resume a known shape on deployment . a range of biocompatible materials may be suitable such as alloys of nickel and titanium ( e . g . nitinol ). other suitable biocompatible materials include but are not limited to polymers and plastics such as hydrophilic plastics , ceramics and the like . fig3 illustrates the support device of fig1 a to 1 c , with an occluding balloon inflated around catheter 110 . the occluding balloon 114 may be utilized during collection of fluid from an organ or region of the body in isolation , where substantially all of the fluid flowing out of the organ or region is collected by the catheter 110 . the occluding means substantially prevents blood , therapeutic agent and / or other fluids entering the vessel from flowing on to other organs or regions , and permits collection of substantially all of the fluid entering the vessel . collected fluid may then be analyzed and / or re - oxygenated and / or perfused through the organ , discarded or handled otherwise . the occlusion means may include an occluding balloon , flange , disc or other means . catheter 110 is delivered to the vessel with the balloon 114 in a deflated condition . the expandable member is delivered , through the catheter , and deployed inside the vessel . the balloon is then inflated around the catheter and substantially all the fluid in the vessel flows through the catheter and into a perfusion set or reservoir to which it is connected . a pump , syringe or other means may be incorporated into the perfusion set to draw fluid out of the vessel , through the catheter , at a rate which substantially maintains the required flow through the organ or region , or through a re - perfusion circuit . as fluid is drawn out of the vessel through the catheter , the expanded support structure supports the vessel walls , preventing collapse or cavitation which might otherwise result from the low pressures or high flow rates generated at the catheter tip , maintaining patency and ensuring flow in the circuit . the expandable member may also anchor the device in position within the vessel , substantially precluding movement of the device and ensuring that the catheter is retained in an optimal location for collection of fluid . the expandable member may take a range of different shapes when in an expanded ( or collapsed ) configuration , and may provide any number of supporting filaments or struts . the design of the expandable member may be based on a range of criteria including but not limited to the size and strength of the vessel wall and the flow rates and pressures likely to be generated near the device . some of these embodiments are illustrated in fig8 a to 8 c although these are examples only and are not intended to limit the scope of the invention as broadly described herein . fig8 a to 8 c illustrate expandable members having elongate portions in the supporting struts adapted for contact with the vessel wall . in the example in fig8 b , the supporting struts are slightly rounded to reduce trauma to the vessel walls . fig8 c provides additional struts when compared with fig8 a , as may be necessitated in particularly flaccid vessels requiring more substantial support . embodiments illustrated herein provide expandable members with a substantially elongate structure adapted for coaxial insertion into and placement within the vessel . the elongate structure supports the vessel over a length on the elongate portions of the struts substantially parallel to and in contact with the vessel wall . these elongate portions may be substantially straight , or may be curved ( e . g . fig8 b ). supporting the vessel wall over a length of the support device , compared with the point of supports of the prior art , improves the capacity of the device to maintain patency , even when very low pressures and high flow rates are generated at the catheter tip , and also reduces the likelihood of the device causing damage to the vessel wall . the elongate portions may have a length which is about the same as or greater than the diameter of the vessel being supported , or some multiple of the vessel diameter , or for example from 1 mm up to 30 mm depending on the vessel size and structure . the length of the elongate portion may be selected according to the vessel being supported , the size of the catheter being used and the flow rates and pressures likely to be generated at the catheter tip . preferably , the elongate portions of the expandable member which contact the vessel wall , are just adjacent the distal tip of the catheter when the device is fully deployed . thus , a proximal end of one or more of the elongate portions may commence , for example , within 0 . 1 to 25 mm of the catheter tip , or at least at a distance which is less than the diameter of the catheter opening . this prevents the vessel wall from being drawn into the space between the catheter tip and the start of the elongate portion of the expandable member which contacts the vessel wall . further , the device may be configured so that when it is in an expanded condition , the distance between adjacent elongate portions is sufficiently small to prevent the vessel wall from being drawn into gaps between them . for example , the distance between adjacent elongate portions may be less than the diameter of the catheter . alternatively , the distance between the adjacent elongate portions may be less than , for example , 3 , 2 . 5 , 2 , 1 . 5 , 1 or 0 . 5 mm , depending on the size and type of the target vessel , and the diameter of the collection catheter being used . preferably , the support device possesses sufficient mechanical strength to maintain patency during collection of fluid , withstanding the deformation forces which may occur in response to suction or low pressures produced at the collection catheter tip . in some embodiments however , it may also be desirable for the device to exhibit some flexibility , and conform to the shape of the vessel when deployed . thus , the support device is capable of providing support and maintaining patency along a length of the vessel , even where there is a curve in the vessel wall . an alternative embodiment of a support device 200 is illustrated in fig2 . proximal end 205 of the expandable member 204 is fixedly attached to a stem or shaft 206 , whereas distal end 203 of the expandable member is movable and able to slide over part of the shaft . this enables the member to collapse radially for delivery inside a delivery catheter , and also facilitates recapture of the device . fig5 illustrates another alternative embodiment of a support device shown at 500 in an expanded condition . in this embodiment , both the proximal end 505 and the distal end 503 of the expandable member are movable along a stem or shaft 506 used to deliver the device to the vessel . stops 508 a , 508 b are provided at fixed locations on a distal portion of the shaft , arranged between ends 503 , 505 of the expandable member . these stops may consist of a small ring , crimp or node of increased diameter , relative to the shaft diameter , and prevent the ends of the expandable member from moving across the stop . this facilitates deployment and retrieval of the expandable member from a catheter . fig1 illustrates a support device 151 consisting of an expandable framework 155 having a woven or braided , basket - like configuration when in the expanded condition . in this arrangement , the support device may also include occluding means in the form of a thin flow - proof coating 156 on the inner and / or outer surface of framework 155 to prevent flow of liquid from the vessel . thus , substantially all fluid in the vessel may be collected by catheter 160 . the flow - proof coating may be made from biocompatible silicon , elastomer or flow - proof polymer . preferably , the support device includes a radiopaque or other marker so that it can be positioned within the target vessel using an imaging system such as those generally known in the art . this enables the physician to position and deploy the expandable member into the blood vessel accurately . the marker may be incorporated into the expandable member and / or into an atraumatic guiding tip which may be incorporated into the support device . preferably , the atraumatic tip is manufactured from , includes or is coated with a lubricant and / or a material having a low coefficient of friction . many materials having low coefficient of friction properties may be used including but not limited to biocompatible high density polyethylene ( hdpe ), teflon \u00ae, polypropylene , polyethylene , microglide \u2122, low friction chromium and silicon to name a few . this improves the performance of the atraumatic tip , so that it \u201c slides \u201d along the vessel wall upon making contact , thereby substantially avoiding trauma . use of an atraumatic guiding tip improves the safety and ability to position the expandable member in the target vessel . moreover , since the atraumatic tip may exhibit greater flexibility than the rest of the device , the device is easier to manipulate into position . the atraumatic tip may be provided at a distance from the distal end of the expandable member which enables a physician to guide the expandable member into position within the target vessel . this distance may be anywhere from , for example , 0 . 25 to 5 centimeters from the distal end of the expandable member when in an expanded condition , although it is to be understood that larger or smaller distances may be utilized , depending on the location of the target vessel and the anatomy surrounding it . referring now to fig6 a and 6 b , another example of a support device 600 is shown . a lumen 602 has a control stem 601 extending therein . four loop portions 603 are provided . each loop portion is attached at a first loop end to a distal end 604 of the lumen , and at a second loop end to the control stem at 605 . the loop portions are controllably expandable by advancing the control stem within the lumen in the direction shown by arrow 606 ( fig6 b ). the support device is percutaneously deliverable with the plurality of loop portions housed substantially within the lumen 602 as illustrated in fig6 a and expandable as illustrated in fig6 b . whilst the embodiment illustrated in fig6 a and 6 b provides 4 loop portions , it is to be understood that any number of loop portions may be used . the number of loop portions incorporated into the device may depend on , for example , the anatomy of the vessel being supported , and / or the size of the catheter used to deliver the device . fig7 a and 7 b illustrate another example of a support device 700 which provides 3 loop portions 703 attached to control stem 701 at juncture 705 . the 3 loop portions are contained during delivery substantially within lumen 702 ( fig7 a ), and are controllably expandable to maintain patency within the blood vessel by advancing control stem 701 in the direction of arrow 706 ( fig7 b ). the rounded edges of the loop portions present a reduced risk of damaging the vessel walls , e . g . by perforation or bruising during delivery . the one or more loop portions may be attached to or near the distal end of the delivery lumen in any suitable manner . the point of attachment may be inside or outside the lumen . the loops may be manufactured from any suitable material such as a metal , metal alloy , plastic , polymer , or other filamentous material or composite . the one or more loop portions may be attached at a second loop end to the control stem by soldering , fusing , an adhesive , or any other suitable means . in another embodiment , the loop portions may be attached to a first and a second loop end to the control stem . the support structure of fig6 a , 6 b , 7 a and 7 b may further include an atraumatic guiding tip of the kind described above to aid in positioning the support structure within the blood vessel . alternatively , parts of the loop portions which may protrude from the lumen when the loop portions are in their collapsed state may be used to guide the support structure into the blood vessel . one or more of the loop portions may be provided with a radiopaque or other marker to assist in this regard . retention means may also be provided with the support structure to retain the expandable member in an expanded condition within the vessel . the retention means may be in the form of a clamp , clip , thumb - slide or the like accessible from outside the patient &# 39 ; s body , and may facilitate adjustment of a deployed expandable member during a procedure . retention means may also impart additional rigidity and strength to the expandable member . thus , the retention member may be used to counteract excessively low pressures which may otherwise cause the expanded member to fail . a support structure of the kind illustrated in the figures may be delivered within a multilumen catheter 900 of the kind illustrated in cross section in fig9 . using this catheter , the support device 910 can be delivered through a first internal lumen 901 without interfering with flow in a second lumen 902 . a third lumen 903 may be provided for monitoring flow rates and pressures , for blood analysis or for delivering other percutaneous tools or devices to the vessel or as an inflation lumen for an occlusion balloon . it is to be understood that in the various embodiments of the present invention , the expanded member does not require constant contact with the vessel walls to provide the required support . for example , the diameter of the expanded member may be less than the diameter of the vessel so that the expanded member only contacts the vessel wall when the vessel begins to collapse . patency is considered to be maintained as long as the support device keeps the vessel open to a degree which is sufficient to maintain continuous flow . to avoid causing turbulence or other undesirable blood flow effects within the vessel , and to optimize flow in the vessel it may be desirable to substantially match the diameter of the expanded member to the diameter of the vessel . alternatively the expandable member may be shaped , e . g . as a coil or helix , to have minimal effect on the flow in the vessel . in one embodiment , the expandable member may have a slightly larger expanded diameter than the relaxed vessel to create an anchoring effect . depending on the size of the outflow vessel from which blood and perfusate is collected from the target region , there may be a natural tendency for the collection catheter tip to move about and contact the vessel , thus increasing the risk of vessel collapse or invagination of the catheter tip into the vessel wall . this can cause pooling of fluid in the isolated target region and may cause serious and permanent damage to the organ or region of the patient being treated . use of a support structure in conjunction with the collection catheter to maintain patency of the outflow vessel , in accordance with embodiments of the present invention can minimize the risk of these complications eventuating . thus , a collection catheter associated with the expanding member can be retained in position during fluid collection . this minimizes movement of the catheter tip , ensures that it is substantially centered relative to the vessel walls and improves withdrawal of fluid out of the vessel . at completion of the procedure , it is desirable that the expanded member is collapsed or compressed and recaptured , preferably in the catheter from which it was deployed . this facilitates removal of the support device from the patient . a reinforcing tip may be provided on the catheter end to strengthen it for recapture . alternatively or additionally , the tip may be coated with a lubricant and / or material having a low coefficient of friction to facilitate smooth recapture of the expandable member . the catheter may also have an internal coating of lubricant and / or a material having a low coefficient of friction to assist translation of support device along its interior during delivery and removal of the device from the patient . although the present invention has been described in terms of the presently preferred embodiments , it is to be understood that the disclosure is not to be interpreted as limiting . various alterations and modifications will no doubt become apparent to those skilled in the art after having read the above disclosure and it is intended that the present disclosure be interpreted as covering all alterations and modifications as fall within the true spirit and scope of the invention . effect of support device on flow rates and pressures achievable during recirculation in sheep right hepatic vein , cephalic vein , coronary sinus and renal vein during recirculation a 0 . 014 \u2033 diameter superelastic nitinol wire stem of 1 . 35 m length was used , coupled to an expandable member having 6 pre - shaped elliptical loop portions welded to the stem . a 0 . 024 \u2033 od atraumatic tip of 2 cm length attached to the distal end of the expandable member was used to position the device in the blood vessel . a balloon occlusion catheter was positioned in the vessel and the expandable member deployed at the tip of the catheter . the balloon was inflated to isolate and capture flows in the vessel and the catheter was connected to a standard extracorporeal circuit for blood circulation . negative pressures were observed in perfusion lines draining the coronary sinus , renal vein , right hepatic vein and cephalic vein during recirculation both with and without a support device . these data show that cavitation is prevented at certain pressures in the vessels tested where a support device is used , but is not prevented where the support device is absent in the vessel at those pressures . although cavitation may occur even with the support device , it occurs at higher flows . also , cavitation ceases sooner where the support device was employed allowing flow to return to normal . in the coronary sinus , recovery from cavitation was not possible without the support device , emphasizing the importance of the device in the procedure . the data further demonstrates that vessel collapse can be irreversible in the absence of a support structure . however , where a support structure is present , the vessel collapse may be reversed by increasing pressure in the vessel or by slowing or reversing the flow rate of fluid through the vessel . more specifically , considering the data for the right hepatic vein , flow rates of up to 250 ml per minute may be achieved before cavitation occurs where a support device is present in the vessel . under the same conditions but where there is no support device , flow rates of only up to 180 ml per minute are possible . a more striking example of the advantages of the support device is seen for the cephalic vein where no flow is achievable without the device . when the vessel wall is supported by the device flow rates of up to 200 ml per minute are noted before cavitation occurs . when the vessel wall is supported flow rates of up to 200 ml per minute are noted before cavitation occurs ."}
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Is the categorization of this patent accurate?
| 0.25 |
1d5133cde40c92eaabe8131cbdf960efd3029fddffc551de233b4ea69b05bd19
| 0.003082 | 0.060059 | 0.040771 | 0.253906 | 0.056641 | 0.035645 |
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