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[ "The structures of compounds bound to E7R have been deposited in the Protein Data Bank under accession code 4NB3.", "\n\nIntroduction {#sec1}\n============\n\nReplication protein A (RPA) is a single stranded DNA (ssDNA)--binding protein complex that is essential for DNA replication, damage response, and repair.^[@ref1],[@ref2]^ In response to DNA lesion formation, RPA rapidly coats ssDNA,^[@ref1],[@ref3]^ preventing the formation of aberrant DNA structures at replication foci and recruiting a number of checkpoint proteins to initiate the response to DNA damage.^[@ref4]^ Increased activity of DNA damage response and repair pathways is observed in a number of human cancers and has been linked to resistance to radiation or chemotherapy treatment.^[@ref5]^ Thus, compounds targeting these pathways may have utility in patients undergoing cancer therapy.", "\n\nRPA70 is the largest of the RPA subunits and contains three high-affinity ssDNA binding domains that serve as the DNA-anchoring core of the entire complex (RPA70A, -B, -C).^[@ref1],[@ref2]^ Binding to ssDNA is mediated by oligosaccharide/oligonucleotide binding (OB) folds that are present on all subunits.^[@ref6]−[@ref8]^ The basic cleft in the OB fold present on the N-terminal domain, RPA70N, binds to several partner proteins that are important for mediating the response to DNA damage, including ATRIP (ATR-interacting protein), RAD9, MRE11, and p53.^[@ref4],[@ref9]−[@ref11]^ We hypothesize that the selective inhibition of the RPA70N basic cleft will specifically disrupt these protein--protein interactions, leading to the inhibition of a subset of RPA functions, attenuation of the DNA damage response, and the selective killing of cancer cells.", "\n\nToward the discovery of a probe molecule that binds tightly to RPA70N and inhibits its interaction with other proteins, we and others have previously reported small molecules that bind to RPA70N.^[@ref12]−[@ref14]^ We used an NMR-based screen to identify fragments that bind to RPA70N, and, on the basis of X-ray structures of the screening hits and analogues when bound to the protein, have obtained analogues with improved affinity. ", "Recently, we have discovered compounds that bind to RPA70N with submicromolar affinity^[@ref12]^ that were obtained by linking together small molecules that bind to two adjacent sites.", "\n\nAn alternative approach for targeting protein--protein interactions is the use of stapled helix peptides. ", "Hydrocarbon stapling has been shown to increase the affinity, stability, and cellular permeability of peptide sequences that bind to protein targets.^[@ref15]−[@ref17]^ NMR experiments have demonstrated that homologous peptides derived from the partner proteins ATRIP, RAD9, and MRE11 bind competitively to the basic cleft of RPA70N.^[@ref18]^ Further, the three peptides share a region of similar primary sequence with p53 and contain a mix of conserved acidic and hydrophobic amino acid residues.^[@ref19]^ An X-ray crystal structure of a chimeric protein containing portions of RPA70N and p53 reveals that a part of the p53 transactivation domain (residues 47--57) folds into helices that bind into the basic cleft in the OB fold of RPA70N.^[@ref19]^ These binding interactions in the cleft are stabilized by both electrostatic and hydrophobic interactions. ", "We have previously measured the binding affinity of these peptides to RPA70N and found that the ATRIP-derived sequence binds more tightly than the Rad9, MRE11, and p53 peptides.^[@ref20]^\n\nHere we describe the discovery of stapled helix peptides, based on the ATRIP sequence, that bind tightly to the protein--protein interaction site in the basic cleft of RPA70N and inhibit the interactions of RPA70N with other peptides/proteins. ", "The binding affinity was optimized by traditional methods, as well as a novel method that can efficiently select and incorporate unnatural amino acids into the peptides. ", "Peptides in which an unnatural amino acid was incorporated displayed a 1--2 orders of magnitude improvement in binding affinity compared to peptides with natural amino acids, penetrate cells, and may serve as useful tools for studying RPA function and the therapeutic potential of inhibiting RPA.", "\n\nResults and Discussion {#sec2}\n======================\n\nAlanine Scanning of the ATRIP Peptide {#sec2.1}\n-------------------------------------\n\nTo better understand the peptide structure--activity-relationships (SARs) of the ATRIP-derived peptide and to elucidate the sequence positions suitable for affinity-optimizing point mutations, we performed an alanine scan in which each amino acid was replaced by an alanine residue (Table [1](#tbl1){ref-type=\"other\"}). ", "Affinity of the mutated peptides was measured using an FPA competition assay with FITC-ATRIP as a probe.^[@ref20]^\n\n###### Alanine Scan of an ATRIP-Derived Peptide\n\n![](", "jm-2013-01730y_0011){#GRAPHIC-d518e377-autogenerated}\n\nAlanine mutations are shown in bold red.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay.", "\n\nSouza-Fagundes et al.^[@ref20]^\n\nResidues D1, F2, T3, D6, L7, E9, L10, D11, and L13 were found to be important for binding to RPA70N, as replacement of each of these with an alanine resulted in a significant loss of binding affinity. ", "Interestingly, although D5 is conserved in the ATRIP and corresponding RAD9, MRE11, and p53 sequences, replacement with an alanine leads to a peptide equipotent with the parent, suggesting that this residue does not contribute significantly to binding to RPA70N. Similarly, despite the conservation of E8 in three out of the four RPA70N binding partners, no loss of binding was observed when E8 was replaced with alanine. ", "In contrast, an almost complete loss of binding was observed when F2 was replaced with an alanine (peptide-02). ", "Two ATRIP amino acid mutations led to a slight improvement in affinity: E8A (peptide-07, *K*~d~ = 22 μM) and T12A (peptide-11, *K*~d~ = 17 μM). ", "However, when combined into one peptide sequence (peptide-14), the individual positive effects on the binding affinity were not additive.", "\n\nATRIP Amino Acid Substitutions Inspired by p53 {#sec2.2}\n----------------------------------------------\n\nIn an attempt to improve the binding affinity of the ATRIP peptide, we substituted the hydrophobic residues WF from the p53 peptide into the corresponding positions of the ATRIP peptide (Table [2](#tbl2){ref-type=\"other\"}). ", "These residues form a hydrophobic motif within p53 (IEQWF) that is not present within the ATRIP sequence. ", "Although individual substitution of L10 or D11 with W or F, respectively, did not improve binding relative to peptide-14 (peptide-15 and peptide-16), a 10-fold improvement in affinity was observed when these replacements were combined (peptide-17, *K*~d~ = 2.7 μM). ", "This effect may be attributed to a clustering of the two residues, leading to the formation of a hydrophobic binding core.^[@ref19],[@ref21]^ To further optimize the potency, we substituted positions 8 and 12 of peptide-17 with alanines, as those mutations were found to increase the binding affinity to RPA70N. Whereas the E8A mutation results in a dramatic loss of affinity in the context of the WF motif (peptide-18), the binding of peptide-19 (T12A mutation) was increased by a factor of 2 relative to peptide 17. ", "A FITC moiety was attached to peptide-19 to facilitate direct measurement of binding affinity to RPA70N; the new peptide-20 has an affinity of 480 nM (approximately an additional 3-fold increase). ", "While the basis for the binding improvement due to the FITC label is not well understood, a similar effect was noted with the ATRIP peptide.^[@ref20]^\n\n###### Amino Acid Substitutions\n\n![](", "jm-2013-01730y_0012){#GRAPHIC-d518e438-autogenerated}\n\nSubstituted residues are indicated in bold red.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay.", "\n\nSouza-Fagundes et al.^[@ref20]^\n\n*K*~d~ values of FITC-labeled peptides determined by direct binding experiments.", "\n\nReduction of Overall Peptide Charge {#sec2.3}\n-----------------------------------\n\nPeptide-20 has a net negative charge of −6. ", "Empirical evidence has suggested that a neutral or positive overall charge is optimal for achieving cellular penetrance.^[@ref17]^ We therefore examined the relative importance of the negatively charged residues in peptide-19 by replacing aspartic and glutamic acid residues with their amide analogues. ", "In addition, we tested the replacement of D and E residues with alanines (in the context of the optimized WFA containing peptide-19) to elucidate which negatively charged amino acids could be substituted with an uncharged residue without leading to an unacceptable decrease in RPA70N affinity (Table [3](#tbl3){ref-type=\"other\"}). ", "While replacement of some negatively charged amino acids is tolerated, other substitutions are accompanied by a severe drop in binding affinity, as might be expected for a peptide binding to a protonated basic cleft. ", "For example, changing D1 to an asparagine was tolerated with a relatively minimal loss of affinity (peptide-21), an alanine substitution of D5 did not reduce the potency compared to an N substitution (peptide-22 and peptide-23), and substitution of D6 with an asparagine produced better binding than the corresponding alanine (peptide-24 and peptide-25). ", "However, for E8, an alanine substitution sharply reduced the binding affinity (peptide-26), while minimal loss of affinity was observed for substituting E9 with either an alanine or glutamine (peptide-27 and peptide-28). ", "On the basis of these results, we combined the least deleterious amino acid substitutions to produce a FITC-labeled peptide (peptide-29) with a net negative charge of −2. ", "However, the reduction in charge came at the expense of a nearly 50-fold loss in binding to RPA70N compared to peptide-20.", "\n\n###### Charge Abrogation of Peptide-19\n\n![](", "jm-2013-01730y_0006){#GRAPHIC-d518e487-autogenerated}\n\nCharge replacement mutations are shown in bold red. ", "Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay unless otherwise noted.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nShortening of the Peptide Sequence {#sec2.4}\n----------------------------------\n\nConcomitant with our efforts to reduce the net negative charge of the peptides, we examined the effect of peptide length on binding affinity and the possibility of improving the properties of the peptides.^[@ref22]^ If the ATRIP-derived peptides adopt a helix with the same length as p53 upon binding to RPA70N, several N- and the C-terminal residues may not be part of the secondary structure and thus are potential candidates for removal. ", "The alanine scan revealed that all residues at the N-terminus are essential for interacting with RPA70N (Table [1](#tbl1){ref-type=\"other\"}). ", "In contrast, minimal loss of binding affinity was observed when residues at the C-terminus were replaced by alanine (peptide-12 and peptide-13). ", "Therefore, we tested whether shortening of peptide-20 by one, two, or three residues at the C-terminus would be tolerated (Table [4](#tbl4){ref-type=\"other\"}).", "\n\n###### Binding Affinity of Shortened Peptides\n\n![](", "jm-2013-01730y_0007){#GRAPHIC-d518e532-autogenerated}\n\nDeleted residues are indicated by bold red dashes. ", "3,4-Dichlorophenylalanine is shown as a bold green Z. Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nRemoving the C-terminal residue (S15) had almost no effect on the binding of peptide-30 to RPA70N, and the removal of the last two C-terminal amino acids (A-S) led to a peptide with improved binding affinity to RPA70N (peptide-31). ", "However, removing one additional residue (L13) resulted in a 3-fold decrease in binding affinity (peptide-32).", "\n\nUnnatural Amino Acid Substitutions {#sec2.5}\n----------------------------------\n\nIn order to further improve binding to RPA70N, we explored the possibility of incorporating unnatural amino acids. ", "Such peptides can be difficult and expensive to synthesize and thus must be carefully designed. ", "To identify suitable locations for incorporation of a designed unnatural amino acid, we exploited findings from our small molecule discovery efforts. ", "We have previously reported the use of an NMR-based fragment screen to discover compounds that bind to a hydrophobic pocket near S55,^[@ref12]^ suggesting that this pocket represents an important binding \"hot spot\" on RPA70N (Figure [1](#fig1){ref-type=\"fig\"}A). ", "Consistent with this finding, that same pocket is occupied by F54 of the WF motif within the p53 peptide (Figure [1](#fig1){ref-type=\"fig\"}B).^[@ref19]^ Optimization of multiple series of fragment hits has established that a 3,4-dichloro-substituted phenyl ring displays significantly improved binding affinity to RPA70N compared to an unsubstituted phenyl group.^[@ref12],[@ref14]^ Thus, we hypothesized that a peptide containing a 3,4-dichloro-substituted phenylalanine in place of a phenylalanine would have improved binding affinity to RPA70N (Figure [1](#fig1){ref-type=\"fig\"}C). ", "Indeed, a peptide containing an unnatural amino acid with a 3,4-dichlorophenyl moiety (peptide-33) showed a \\>100-fold improvement in affinity (Table [4](#tbl4){ref-type=\"other\"}). ", "An X-ray structure of peptide-33 when complexed with RPA70N confirmed that the side chain of the 3,4-dichlorophenylalanine binds to the RPA70N hot spot located above S55, in a manner similar to the binding mode of the phenylalanine of p53 (Figure [1](#fig1){ref-type=\"fig\"}D).", "\n\n![", "X-ray structures of fragments and peptides in complex with RPA70N reveal a preferred binding site within the basic cleft. (", "A) Overlay of cocrystal structures of fragments bound to RPA70N. (B) Superpositioned structures of RPA70N bound to fragments and the p53 peptide (red). (", "C) The dichlorophenyl ring of an elaborated compound (yellow) binds in the same hydrophobic pocket as F54 of the p53 peptide (red). (", "D) Superposition of RPA70N/p53 peptide (red)^[@ref19]^ and RPA70N/peptide-33 (blue).](jm-2013-01730y_0002){#fig1}\n\nStapled Helix Peptides {#sec2.6}\n----------------------\n\nThe use of a hydrocarbon staple for helical peptides is a promising approach to improve upon the poor characteristics of linear peptides by imparting increased protease resistance, affinity, and cell permeability.^[@ref15]−[@ref17]^ Three stapling patterns have been shown to stabilize helical conformations: *i*, *i* + 3; *i*, *i* + 4; and *i*, *i* + 7.^[@ref17]^ On the basis of the results from the mutational analyses, we employed the *i*, *i* + 4 configuration using residues 5 and 9 to evaluate stapled helix peptides with varying overall net charge (Table [5](#tbl5){ref-type=\"other\"}). ", "Although peptide-34 had a slightly reduced binding affinity compared to its unstapled counterpart (peptide-31), the negative charge was reduced. ", "As expected, further reduction of the charge yielded an additional loss in affinity (peptide-35, peptide-36, and peptide-37). ", "Once again, we compensated for the loss in affinity due to charge abrogation by substituting F12 with a dichlorophenylalanine (peptide-38 and peptide-39). ", "Incorporation of this motif alone led to a 31- and 175-fold increase in affinity, respectively, resulting in peptides that represent the optimal balance of potency and overall net charge.", "\n\n###### Binding Affinities of Peptides\n\n![](", "jm-2013-01730y_0008){#GRAPHIC-d518e630-autogenerated}\n\nα-(4-Pentenyl)alanine staples are depicted as a red X. 3,4-Dichlorophenylalanine is shown as a bold green Z. Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nSelectivity {#sec2.7}\n-----------\n\nTo verify the utility of the stapled helix peptides as specific inhibitors of the RPA70N protein--protein interactions, we evaluated the ability of the peptides to bind to the other OB-fold-containing domains of RPA that bind to ssDNA.", "\n\n{#fig2}\n\nBy use of a direct binding FPA assay, peptide-37 and peptide-39 were examined for their ability to bind to RPA70A/B, which contains the core ssDNA binding unit, and RPA70C/32D/14 (Figure [2](#fig2){ref-type=\"fig\"}). ", "Peptide-37 shows very little selectivity in binding to the different OB-fold containing domains; while this peptide binds to RPA70N with a *K*~d~ of 7.4 μM, it binds the other domains with similar affinity (12--15 μM). ", "In contrast, peptide-39, which binds to RPA70N with an affinity of 0.042 μM, binds to RPA70A/B and RPA70C/32D/14 with a *K*~d~ of only 2.4 μM, exhibiting 50-fold selectivity for binding to RPA70N. The incorporation of the dichlorophenyl moiety not only produces a significant increase in potency but also appears to impart a significant increase in selectivity for RPA70N over other OB-fold containing domains. ", "To confirm that peptide-39 does not functionally displace RPA from ssDNA, we conducted an electrophoretic mobility shift assay (EMSA). ", "Increasing concentrations of peptide-39 were incubated with RPA and ssDNA and subjected to separation on a polyacrylamide gel. ", "No change in the percent of RPA bound to radiolabeled ssDNA was observed, indicating that although peptide-39 can bind weakly to other OB-fold containing domains in a biochemical assay, this 2 μM binding affinity is not sufficient to displace full-length RPA from ssDNA (Figure [3](#fig3){ref-type=\"fig\"}). ", "Thus, peptide-39 possesses a suitable selectivity profile for use as a probe of RPA70N function in cells.", "\n\n{#fig3}\n\nCell Penetrance {#sec2.8}\n---------------\n\nSeveral studies have demonstrated that stapled helix peptides gain entry to mammalian cells through active endocytosis.^[@ref15],[@ref23],[@ref24]^ Further, overall peptide charge is a key determinant of cellular penetrance, with increased positive charge leading to more efficient uptake. ", "We examined the ATRIP-derived stapled helix peptides for their ability to enter mammalian cells. ", "Peptides were incubated for 24 h with U2OS cells, fixed, and visualized by confocal microscopy for direct observation of the FITC label (Figure [4](#fig4){ref-type=\"fig\"}). ", "As expected, peptide-34, with a net charge of −4, was the least efficient at penetrating cells. ", "In contrast, the remaining peptides were observed inside the cells in a pattern consistent with internalization through endocytosis. ", "Diffuse cytosolic staining and fluorescence within the nucleus were also observed, as exemplified by peptide-37 and peptide-39.", "\n\n{#fig4}\n\nConclusions {#sec3}\n===========\n\nTo discover a peptide that binds tightly to RPA70N and penetrates cells, we initiated optimization of a 15 amino acid ATRIP-derived peptide that binds to RPA70N with an affinity of 29 μM and possesses a net charge of −5. ", "Through alanine scanning, natural amino acid substitutions, and shortening of the peptide sequence, we identified key residues responsible for binding to RPA70N, improved the binding affinity, and ascertained which amino acids could be substituted to reduce the overall negative charge. ", "However, because of the electrostatic characteristics of the pocket, substitutions that reduced the peptide charge universally led to a decrease in binding affinity. ", "Despite these improvements and the knowledge gained, the resulting peptides were still unsuitable for use as a chemical probe for the study of RPA70N as a cancer target because of insufficient binding affinity.", "\n\nTo further improve the binding affinity, we sought to incorporate an unnatural amino acid into our peptides. ", "Historically, this strategy has not been widely employed because of difficulties in choosing which amino acid to replace and which unnatural amino acid to use as a replacement. ", "Indeed, most peptide optimizations typically involve only the use of natural amino acid substitutions. ", "Here we have demonstrated a strategy to efficiently design unnatural amino acid substitutions for peptide optimization. ", "The optimization process involves the identification of a binding hot spot using a fragment-based screen and subsequent structural characterization of important molecular interactions that might be exploited for affinity improvements. ", "Structural knowledge of the residue that normally occupies this hotspot, along with SAR information gleaned from fragment hits and optimization of these hits, then guides the efficient targeted replacement of an amino acid with an optimized variant.", "\n\nWe have demonstrated this strategy by capitalizing on a wealth of SAR and structural information from compounds identified from a NMR-based fragment screen. ", "In multiple prior instances, the presence of a 3,4-dichlorophenyl moiety has produced improvements in binding affinity.^[@ref12],[@ref14]^ Thus, we applied this substitution pattern to a phenylalanine residue that had been previously determined to occupy the same binding hot spot identified in the fragment screen. ", "The addition of two halogens produced highly significant gains in binding affinity in both stapled and unstapled peptides.", "\n\nIn total, by combining peptide optimization studies, small molecule SAR, and structural information on peptide and small molecule binding modes, we improved the affinity of the modified peptide by almost 1000-fold. ", "The optimized stapled helix peptide obtained from this work binds tightly to RPA70N with an affinity of 0.042 μM, is selective for binding to RPA70N versus other OB folds of RPA, has a reduced overall net negative charge, and penetrates cells. ", "This compound may serve as a useful tool to study the biology of RPA and validate RPA as a cancer target. ", "Moreover, the new approach that we have employed to optimize the peptides may be a useful general method for optimizing peptides that bind to other protein targets and thus expand the utility of stapled helix peptides as chemical tools and therapeutic agents.", "\n\nExperimental Details {#sec4}\n====================\n\nProtein Expression and Purification {#sec4.1}\n-----------------------------------\n\nRecombinant RPA70N (RPA70~1--120~), RPA70AB (RPA70~181--422~), and RPA70NAB (RPA70~1--422~) constructs were prepared as described previously.^[@ref20],[@ref25]−[@ref27]^ Proteins were expressed in *Escherichia coli* host Rosetta (RPA70AB, RPA70NAB) or BL21-DE3 (RPA70N) cells (Novagen). ", "Cells were grown in LB medium containing kanamycin (RPA70AB, RPA70NAB) or ampicillin (RPA70N) at 37 °C, induced with 0.1 M IPTG when the OD reached 0.6, and harvested after 4 h using a JLA 8.1 Beckman rotor at 7500 rpm and 4 °C. ", "Pellets were stored at −20 °C. ", "Human RPA70N was purified using a Ni sepharose column (GE Healthcare). ", "Following His-tag cleavage and a Ni sepharose column repass to remove the cleaved tag, RPA70N was obtained at greater than 95% purity as judged by sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) analysis. ", "Finally, RPA70N samples were dialyzed against assay buffer (50 mM HEPES, 75 mM NaCl, 5 mM DTT, pH 7.5) for use in fluorescence polarization studies. ", "RPA70AB samples were purified using nickel affinity chromatography in 10 mM HEPES (pH 7.5), 500 mM NaCl, 5 mM BME, and 10% glycerol using an elution gradient from 20 to 300 mM imidazole. ", "Cleavage of the His tag with TEV protease was performed through overnight dialysis in a buffer containing 10 mM HEPES (pH 7.5), 200 mM NaCl, 5 mM BME. ", "A second Ni column purification step was used to remove the His tag. ", "Size exclusion chromatography using a Superdex S75 column equilibrated with the dialysis buffer was used as a last step of purification. ", "RPA70AB protein was concentrated, and stock solutions were frozen in liquid nitrogen and kept at −80 °C. ", "A similar procedure described previously^[@ref26]^ was used for RPA70NAB samples using Ni column buffer 30 mM MES (pH 6.5), 500 mM NaCl, 5 mM BME and cleaving with H3C protease. ", "The size exclusion chromotography step was performed using a Superdex S200 column and a buffer containing 30 mM MES (pH 6.5), 200 mM NaCl, 10 mM BME, 5% glycerol.", "\n\nPeptide Synthesis {#sec4.2}\n-----------------\n\nAll linear peptides, with and without fluorescein isothiocyanate (FITC), were purchased from GenScript USA Inc. FITC groups were attached to the N-terminus of peptide sequences via an aminohexanoic acid (Ahx) linker. ", "Hydrocarbon stapled peptides were purchased from New England Peptide LLC. ", "Staples were incorporated by placing modified α-(4-pentenyl)alanine residues at predetermined locations within the peptide sequence, separated by three amino acids. ", "Peptides were purified by the manufacturer using high-performance liquid chromatography to \\>95% purity. ", "Unlabeled peptides were dissolved as 10 mM stock solutions in assay buffer (50 mM HEPES, 75 mM NaCl, 5 mM DTT, pH 7.5). ", "FITC-labeled peptides were dissolved in DMSO to a final concentration of 1 mM.\n\nFluorescence Polarization Anisotropy Assays {#sec4.3}\n-------------------------------------------\n\n*K*~d~ determination and FPA competition assays were conducted as described previously^[@ref20]^ with minor modifications. ", "For direct *K*~d~ determination of FITC-labeled peptides, increasing concentrations of purified RPA were added to 25 nM peptide in a total of 50 μL assay buffer. ", "Anisotropy was measured, and data were fit to a single site binding model using Prism. ", "For competition experiments, unlabeled peptides were titrated into assay buffer containing RPA70N and FITC-labeled peptide probe. ", "Assays were conducted at a protein concentration equal to the *K*~d~ of the FITC-peptide--protein interaction. ", "Therefore, 50 nM FITC-ATRIP was used with 6 μM RPA70N; 25 nM peptide-31 was used with 350 nM RPA70N. Anisotropy was measured and plotted against compound concentration using a four-parameter logistic fit to generate an IC~50~; this value was converted to *K*~d~, as previously described.^[@ref20]^\n\nGel Mobility Shift Assay {#sec4.4}\n------------------------\n\nThe gel mobility shift assays were performed as previously described^[@ref28]^ with the following modifications. ", "Purified RPA (12 nM final concentration) and increasing concentrations of peptide-39 (0, 0.1, 1, 10, 100 μM final concentration) were incubated with radiolabeled 50-nucleotide ssDNA probe (6 nM final concentration) at room temperature for 20 min. ", "The samples were separated by electrophoresis prior to autoradiography and quantitation.", "\n\nFluorescence Microscopy {#sec4.5}\n-----------------------\n\nU2OS cells were plated at 3 × 10^4^ cells/well in eight-chamber slides (BD Falcon). ", "After 24 h, cells were washed once with PBS and incubated for 24 h with stapled helix peptides in serum-free medium. ", "Medium was removed, and cells were fixed in 4% paraformaldehyde/PBS for 1 h at room temperature. ", "Cells were rinsed three times with PBS and mounted on a coverslip with Vectashield (Vector Laboratories) mounting medium containing DAPI. ", "Slides were imaged on a confocal microscope (Zeiss LSM 710).", "\n\nCrystallization of RPA70N:Peptide-33 Complex {#sec4.6}\n--------------------------------------------\n\nLyophilized peptide-33 (FITC-Ahx-DFTADDLEEWZAL-NH~2~) was added directly to 700 μM RPA70N E7R at a 2.5:1 (peptide-33/E7R RPA70N) ratio and initially screened against a variety of conditions. ", "Following optimization of the initial crystallization conditions, the buffer condition of 100 mM Bis-Tris, pH 6.5, 200 mM ammonium acetate, 25% PEG 3350 was found to produce crystals that showed a strong green color, indicative of the presence of FITC. ", "Prior to data collection, crystals were soaked in mother liquor containing 20% 2-methyl-2,4-pentanediol (MPD) and were flash-frozen in liquid nitrogen. ", "X-ray diffraction data were initially collected on an in-house rotating anode source and later at sector 21 (Life Sciences Collaborative Access Team, LSCAT) at the Advanced Photon Source. ", "All data were processed by HKL2000.^[@ref29]^ The proteins crystallized in space group *C*121 and contained two peptide-33:E7R RPA70N complexes in the asymmetric unit. ", "Initial phases were obtained by molecular replacement with PHASER^[@ref30]^ using the E7R RPA70N structure (4IPC)^[@ref27]^ as a search model. ", "Iterative cycles of model building and refinement were performed using COOT^[@ref31]^ and Phenix.^[@ref32]^ Following modeling of waters, peptide-33, including its covalently attached FITC, was placed into electron density at the basic cleft and refined. ", "The structure of this complex has been deposited in the Protein Data Bank under the accession code 4NB3.", "\n\nCrystallographic results and refinement statistics. ", "This material is available free of charge via the Internet at <http://pubs.acs.org>.", "\n\nSupplementary Material\n======================\n\n###### \n\njm401730y_si_001.pdf\n\n^\\#^ A.O.F.: Novartis Institutes for BioMedical Research (NIBR), Global Discovery Chemistry, Emeryville, California 94608, United States.", "\n\n^∞^ B.V.: The Institute for Applied Cancer Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.", "\n\n^¶^ E.M.S.-F.: Physiology and Biophysics Department, Federal University of Minas Gerais, Av. ", "Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil.", "\n\nThe authors declare no competing financial interest.", "\n\nThis work was supported by a postdoctoral fellowship from the Deutscher Akademischer Austausch Dienst (DAAD) to A.O.F., a National Institutes of Health National Research Service Award (NRSA) F32 ES021690 to M.D.F., NIH Grant CA102792 to D.C., and funding from the National Council for Scientific and Technological Development---CNPq and Federal University of Minas Gerais/Brazil to E.M.S.-F. We thank Dr. Cheryl Arrowsmith (Ontario Cancer Institute, Toronto, Canada) for kindly providing the ^1^H and ^15^N backbone NMR assignments of RPA70N.\n\nRPA\n\n: replication protein A\n\nFPA\n\n: fluorescence polarization anisotropy\n\nLE\n\n: ligand efficiency\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Social Media Optimization Trends For 2017\n\nIt’s anticipated that the Development of Snap will Result in new opportunities, which is interesting at least, in 2017. ", "In the past couple of months Breeze, understood previously and more broadly as Snap Chat, has obtained improved by leaps and bounds. ", "Experts are predicting big things with this platform at the days beforehand. ", "Breeze has been effective in altering important trends in addition to user expectations from the sphere of social networking marketing. ", "Due to Snap, the moment focused perspective of communicating is back. ", "It has meant more spontaneous and lives content. ", "It’s helped programmers create more programs that are concentrated towards the mobile platforms.", "\n\nSnap has also brought forth perpendicular videos and forced them a Portion of the mainstream. ", "But now it’s seeking to produce products which happen to fall beyond the purview of the attention domain – which of exchanging messages. ", "It’s seeking to bring about real world eyeglasses because of its customers so that they have the ability to capture visual information about a first-person basis. ", "So far as.", "\n\nSocial networking Optimization is worried; Snap will be there right at the center of matters. ", "It’s also expected to offer a few significant league advertising opportunities also. ", "Twitter fatigue will get worse Experts believe that maybe not everybody is well with Twitter and moving. ", "But Many Brands and celebrities active on Twitter. ", "They are trying to gain Twitter followers in 2017.", "\n\nTwitter fatigue will get worse\n\nAhead in 2017, it’s not expected to have any better. ", "Actually, within the past couple of decades, a lot of folks have been stating that Twitter will probably die a natural death. ", "But, there are also the ones that consider that in most likelihood Twitter will be there for one more year in the least. ", "But, they’re also stating that Twitter fatigue increases appreciably in 2017. ", "Twitter is famous for its brief updates delivered at a breakneck speed but in addition, it contributes to a great deal of incoming and outgoing tweets.", "\n\nWhen it began it was rather fascinating for the simple reason that it was brand new. ", "But now users are becoming used to it and are requesting something that’s a whole lot different. ", "They would like it to be larger, have higher details, and have more interesting content. ", "Additionally, they wish for the speed to become slower. ", "Instagram actually has already begun to slow down its rate of updates.", "\n\nMore sensational experiences\n\nYes, this is exactly what users will desire in 2017 and they desire Social media to meet this function, to be the supplier as it had been. ", "No more can it suffice users to say social websites they’re attending an Occasion – they should show other people how it seems to be attending that event reside. ", "This can be achieved by means of live videos and 360-degree graphics.", "\n\nEven Real-time posting could resolve the conundrum to an extent too. ", "The fundamental Idea is to create others – that aren’t there – feel a portion of the entire show. ", "They ought to feel They Are a real and natural part of the whole experience even as it continues to unravel.", "\n\nSIMILAR NEWS\n\nThere are certain promotional ideas that can truly help you get the website traffic as well as rise success of video clip on buying you Tube comments, However, there is a trouble that this takes a great deal of time to get the sort and also customers for the video. …", "\n\nAre you planning to Boost YouTube Sights? ", "There can be any type of a number of factors for services as well as individuals to want to reach a larger target market. ", "Among the lot more effective means to acquire a bigger target market is to buy YouTube views advertise YouTube …\n\nRunning a picture for your web site is as awesome as running a large range of phrases. ", "So, you should utilize images from a variety of the things which you may be offering, in addition, to showcase them all working on the online audience. ", "Because situation applies Instagram as well …" ]

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[ "Pierre Karl Péladeau nuit au retour des Nordiques à Québec, a affirmé jeudi le chef de la Coalition avenir Québec, François Legault. ", "Selon lui, les propriétaires de la Ligue nationale de hockey (LNH) seront réfractaires à accorder une franchise à un homme d'affaires qui dirige un parti indépendantiste.", "\n\n«Ce que j'entends à Montréal, c'est que tant que M. Péladeau sera là, ce sera difficile de lui donner une équipe», a laissé tomber le chef caquiste avant une réunion de ses députés.", "\n\nIl dit douter que les propriétaires des autres franchises canadiennes acceptent d'accueillir au sein de leur groupe le chef d'un parti politique voué à l'indépendance du Québec. ", "M. Péladeau est l'actionnaire de contrôle de Québecor, l'entreprise qui gère l'amphithéâtre de Québec et qui tente de convaincre la Ligue nationale de hockey (LNH) de ramener le hockey professionnel dans la Vieille Capitale.", "\n\nM. Legault croit que les autres propriétaires useront de leur droit de veto pour barrer la route à M. Péladeau.", "\n\n«Le fait que M. Péladeau soit un indépendantiste, on sait très bien, que ce soit les propriétaires de Toronto ou du Canadien, ce ne sont pas des indépendantistes et ils n'aiment pas ça, l'indépendance du Québec», a dit M. Legault.", "\n\nLa sortie de François Legault a été qualifiée de « ridicule » par le député péquiste Pascal Bérubé. ", "Il note que les Nordiques ont rejoint la LNH en 1979, alors que René Lévesque était au pouvoir et à quelques mois du premier référendum sur l'indépendance.", "\n\n«Je crois que Québec est une capitale présentement, puis on est une capitale d'un pays, et ça ne changera pas, a dit M. Bérubé. ", "Cette ville-là est une ville de hockey avec des amateurs de hockey qui aiment le hockey, qui ne mélangent pas ça avec la politique.»", "\n\nM. Bérubé y voit la preuve que le chef caquiste sent la soupe chaude dans les élections partielles de Chauveau et Jean-Talon, deux circonscriptions vacantes de la région de Québec.", "\n\nCe n'est pas la première fois qu'un politicien soupçonne le PQ de nuire au retour des Nordiques. ", "Jean Charest l'avait fait lors de la campagne électorale de 2012. ", "À l'époque, M. Legault a qualifié ses commentaires de «désespérés».", "\n\nLe ministre libéral Sam Hamad, responsable de la Capitale nationale, a dit ne pas vouloir nuire aux efforts de Québecor pour ramener le hockey professionnel à Québec, jeudi. ", "Il a toutefois laissé entendre que l'incertitude économique que pourrait entraîner l'élection d'un gouvernement péquiste risque de jouer dans la décision des autorités de la LNH.", "\n\n«Il ne faut pas être naïf», a dit M. Hamad. ", "La condition politique c'est la stabilité et la stabilité, c'est un facteur important pour l'économie.", "\n\nLorsque Pierre Karl Péladeau s'est lancé en politique, en mars 2014, le commissaire adjoint de la LNH, Bill Daly, a affirmé à Sportsnet que les allégeances politiques de l'homme d'affaires n'auraient pas d'impact sur un éventuel processus d'expansion.", "\n\nUn porte-parole de la ligue, Frank Brown, a refusé de commenter la sortie de M. Legault jeudi.", "\n\n«Il n'y a pas de commentaire à faire puisque nous ne sommes pas dans un processus formel d'expansion», a-t-il indiqué dans un courriel." ]

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[ "Linear fluorocarbon polymers have been extensively utilized as binders and wet proofing agents in cell electrodes having finely divided active material. ", "According to a typical electrode forming technique a fluorocarbon polymer may be incorporated in a cell plate by mixing the polymer with a particulate active material to form an aqueous paste. ", "Since fluorocarbons are hydrophobic, this is accomplished by first dispersing the fluorocarbon in an aqueous solution containing a minor amount of a surface active agent, usually less than 5 percent by weight. ", "The surfactant allows the polymer to be uniformly dispersed in the water, so that in the pasty mixture of water, surfactant, active material particles, and polymer, the latter is uniformly distributed. ", "The aqueous paste is spread onto a current collector or other support usually with a doctor blade or by calendering so that the paste is uniformly distributed over the desired active area of the cell plate.", "\nWhile teflonated materials as described above have been found to be adequate, it is found that for electrodes comprised of zinc or cadmium, certain deficiencies are encountered which are alleviated by the binder defined herein." ]

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[ "Talking exclusively to Digital Spy, the Lincoln Burrows star recalled just how close he came to cracking his skull open in the shocking incident.", "\n\n\"I think I was in shock, so the scary factor disappeared,\" he said. \"", "I was running into a prison and there was an explosion above my head.", "\n\n\"The pain I felt wasn't pain like a knife slowly cutting into your arm, it was much more. ", "It's very hard to articulate what kind of pain it was – but I rested down on one knee and I remember thinking, 'What the f**k was that?' ", "And blood was just pouring out.\"", "\n\nView photos\n\nPhoto credit: Getty Images\n\nExplaining that he knew something was wrong at that point, Dominic said his stuntman looked at him \"like he had seen a ghost\".", "\n\n\"I said to him, 'What's going on?' ", "And he wouldn't tell me what the f**k was going on. ", "He eventually said, 'Your skull. ", "It's split. ", "I can see to your skull in two places.'", "\n\n\"And then I saw this shadow to the left of my face and I thought, 'What is going on here?' ", "And it was my nose, which had been smashed to the other side.\"", "\n\nAfter \"going through a very calm state\" because they were working in a remote location, Dominic revealed he \"had a moment of thinking, 'Oh I am probably going to die here'\".", "\n\n\"It was bizarre, but I just assumed that I was going to pass out at any moment,\" he went on. \"", "I thought the skull was cracked, blood was going to leak into my brain and I was going to pass out – and I wasn't going to wake up again.", "\n\n\"But I was very calm and my beautiful girlfriend Anna; she was there to support me. ", "Within five minutes I realised what was going on. ", "I stood up and said, 'Get me to a hospital'.\"", "\n\nView photos\n\nPhoto credit: Fox\n\nDominic explained that after his operation, the plastic surgeon said he was \"a very lucky man\" and \"should have died\".", "\n\n\"Because of my build and playing years of rugby, I have this thick neck, so that held my neck in place when the iron bar fell on me,\" he continued. \"", "The only real injury I have still is whiplash. ", "Apparently, I have extra layers of skin around my skull, so that prevented the bar from actually cracking my skull.", "\n\n\"Within two or three days, I was ready to get back to work. ", "My recovery was extraordinary. ", "Within a couple of weeks, I was fine. ", "Wentworth [Miller] was tremendous support and he was greatly concerned about my health. ", "I was just a very lucky guy.\"", "\n\nAside from his terrifying ordeal, Dominic also revealed he was \"over Prison Break\" by the end of season 4...\n\n\"It had been a long process of shooting 22 episodes a year and my creative juices were spent, so I was ready to go onto a different journey,\" he recalled.", "\n\n\"The fact that we had eight years to think about it, it was a novelty in a way going back and seeing how things were.\"" ]

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[ "The Redskins’ Week 15 win at Jacksonville kept Washington’s playoff hopes alive and pushed back relentless offseason talk for at least a few more days. ", "Regardless, there’s no stopping 2019 free agency and the NFL Draft from occurring. ", "There’s also no denying some clear needs and concerns for the current roster going forward.", "\n\nIn conjunction with my latest 2019 first-round NFL mock draft, here’s a quick look at the primary positional concerns for next season. ", "Have fun quibbling at the order, which likely changes multiple times over the coming weeks. ", "I've changed my mind three times since starting the list.", "\n\n<<SEE THE 2019 NFL MOCK DRAFT 6.0>>\n\n1. ", "Quarterback – Much speculation surrounds Alex Smith’s recovery from his broken right leg including concerns over possible infections from the compound fracture. ", "From the football perspective, his playing career could be in jeopardy. ", "Smith’s hefty contract remains on the books with salary cap hits of $20.4 and $21.4 million over the next two years. ", "That limits Washington’s options since a notable free agent signing or a first round selection makes would put a huge chunk of the team’s asset allocation into one position. ", "But does Colt McCoy and a Day 2 selection sound appealing?", "\n\n2. ", "Inside linebacker – Between Mason Foster’s private messages and Zach Brown seeing the writing on the wall, fair to say that it’s been a rough month for this unit. ", "That the Redskins risked plenty to claim Reuben Foster shows their level of concern at the position. ", "Washington needs a speed upgrade inside.", "\n\n3. ", "Left guard – The Redskins had a need here this past offseason and never addressed it. ", "The problem remains. ", "Don’t expect a Jay Gruden-coached team to select another guard in the first, but fixing this whole is necessary.", "\n\n4. ", "Edge rusher – Preston Smith, another 2019 free agent, only has 3.5 sacks and five tackles for loss. ", "That’s 1.5 sacks more than 2017 second-round pick Ryan Anderson. ", "Even if Smith stays, the Redskins need more production opposite Ryan Kerrigan. ", "Edge rusher might be the odds-on-favorite for their first-round pick considering the need and draft strengths.", "\n\n5. ", "Cornerback – Washington played this season with two true veterans and four players with a combined one year of NFL experience. ", "The top option, Josh Norman, enters the fourth year of his five-year, $75 million contract. ", "He only counts as $6 million in dead cap space, meaning the Redskins could move on if interested.", "\n\n6. ", "Wide receiver – Jamison Crowder enters free agency. ", "Whether the Redskins make retaining the slot threat a priority or not, this group lacks a go-to option.", "\n\n<<SEE THE 2019 NFL MOCK DRAFT 6.0>>\n\nMORE REDSKINS NEWS:" ]

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[ "Q:\n\nМожно ли как то обработать undefined?", "\n\nЕсть скрипт, который на сайте отображает город посетителя в шапке справа вот в таком вот виде. ", "Но бывает так, что иногда скрипт вместо города выдаёт undefined. ", "И собственно вопрос: А можно как-то дописать/переписать скрипт, чтобы если undefined то вместо него показывало например текст: Доставка до вашего места? ", "Помогите пожалуйста это исправить.", "\n<!-- ", "Определение города посетителя -->\n <script src=\"http://code.jquery.com/jquery-1.10.2.min.js\" type=\"text/javascript\"></script>\n <script src=\"https://api-maps.yandex.ru/2.0/?load=package.full&lang=ru-RU\" type=\"text/javascript\"></script>\n <script type=\"text/javascript\">\n $(document).ready(function(){\n ymaps.ready(function(){\n var geolocation = ymaps.geolocation;\n //$('#cou').html('Ваша страна: '+geolocation.country);\n $('#tow').html('Выдача заказов в г. '", "+geolocation.city);\n //$('#reg').html('Ваш регион: '+geolocation.region);\n });\n });\n </script>\n<!-- ", "Определение города посетителя -->\n\n<span id=\"tow\">... определяется ...</span>\n\nA:\n\nМожно, воспользуемся проверкой if else - если условие внутри if (здесь) верно, то выполнятся команды внутри { } после if. ", "А если неверно - то выполнятся команды внутри { } после else. ", "Восклицательный знак является отрицанием, т.е. !", "= можно прочитать как \"не равно\".", "\n....\n\nvar geolocation = ymaps.geolocation;\n\nif (geolocation.city !", "= undefined) { // если не undefined\n\n $('#tow').html('Выдача заказов в г. '", "+geolocation.city); // выводим город\n\n} else { // иначе\n\n $('#tow').html('Доставка до вашего места'); // выводим надпись\n\n}\n\n....\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Semi-synthetic DNA-protein conjugates: novel tools in analytics and nanobiotechnology.", "\nThis article reports on the syntheses, characterization and applications of semi-synthetic conjugates composed of nucleic acids, proteins and inorganic nanoparticles. ", "For example, self-assembled oligomeric networks consisting of streptavidin and double-stranded DNA are applicable as reagents in immunoassays, model systems for ion-switchable nanoparticle networks as well as nanometer-scaled 'soft material' standards for scanning probe microscopy. ", "Covalent conjugates of single-stranded DNA and streptavidin are utilized as biomolecular adapters for the immobilization of biotinylated macromolecules at solid substrates via nucleic acid hybridization. ", "This 'DNA-directed immobilization' allows for reversible and site-selective functionalization of solid substrates with metal and semiconductor nanoparticles or, vice versa, for the DNA-directed functionalization of gold nanoparticles with proteins, such as immunoglobulins and enzymes. ", "This approach is applicable for the detection of chip-immobilized antigens. ", "Moreover, covalent DNA-protein conjugates allow for their selective positioning along single-stranded nucleic acids, and thus for the construction of nanometre-scale assemblies composed of proteins and/or nanoclusters. ", "Examples include the fabrication of functional biometallic nanostructures from gold nanoparticles and antibodies, applicable as diagnostic tools in bioanalytics." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Facing off\n\nThis piece represents the opinion of The Bowdoin Orient editorial board.", "\n\nFebruary 3, 2012\n\nThe students behind Mass Deactivation presented a challenge to the Bowdoin community this week, urging students to deactivate their Facebook accounts for exactly one month starting on February 8. ", "The premise of the experiment is to re-experience what life would be like without the social network, and creators Tyler Patton '12 and Ruiqi Tang '13 think that Bowdoin—as close-knit as it is tech-saturated—is the perfect environment in which to do so. ", "And they're right.", "\n\nThere could not be a better time to participate in this experiment. ", "Facebook just filed a $5 billion IPO to become a publicly traded company, which means that starting this spring it will be beholden to shareholders, and must find ways to increase profitability by selling even more user information to advertisers and other third parties. ", "With change afoot, perhaps we should examine just how much of our private information we really want to be converted into currency.", "\n\nWe are also the last generation of college students that will remember what it was to socialize without Facebook. ", "Our lives were probably not any simpler without Facebook, but they were certainly less plugged-in. ", "We had to go to greater lengths to meet people and to keep in touch with friends and family. ", "Perhaps we took more active roles in building personal relationships before we had a mini-feed to tell us what our friends were doing.", "\n\nThe most compelling aspect of this experiment is its call for collective action. ", "As the site points out, deactivating a Facebook account does not completely disconnect you from the online world. ", "You will inevitably still be surrounded by people posting photos, liking statuses, and creating events. ", "And as Facebook reminds users who attempt to deactivate, your friends might miss you when you're gone. ", "As such, this experiment \"could literally be the last time for the rest of your life that you and the people around you exist without Facebook.\" ", "What would it be like to attend a party no one will see photos of the next day? ", "Or to approach someone at that party without having done some reconnaissance on their profiles first?", "\n\nTo achieve the mass participation that will make this experiment meaningful, its creators must extend their advertising campaign such that it reaches more people. ", "They must push beyond those who already harbor misgivings about Facebook and attempt to attract heavy users who might notice the greatest difference in their lives without an account. ", "While the cryptic flyers simply reading \"massdeactivation.blogspot.com\" are intriguing, they do not explain the very exciting nature of the project. ", "It would be unfortunate to lose potential participants just because they forget to look up the mysterious URL upon returning to their dorm rooms.", "\n\nAdditionally, we urge the creators to survey participants at the end of the experiment and to make the results public. ", "Did people find that Facebook enriches or compromises their social lives? ", "Did they feel more or less lonely, bored or connected to people when they did not have an account? ", "Collecting and distributing this information will be thought-provoking for those who participate in the experiment, as well as for those who choose not to join, and may even prompt similar experiments elsewhere. ", "Facebook does not make the path to deactivation obvious, but we believe it is worth following, if only for a month." ]

{ "pile_set_name": "Pile-CC" }

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[ "<?", "php\n\nnamespace Runalyze\\Tests\\Parser\\Activity\\FileType;\n\nuse Runalyze\\Parser\\Activity\\Common\\Data\\ActivityDataContainer;\nuse Runalyze\\Parser\\Activity\\Common\\Filter\\DefaultFilterCollection;\nuse Runalyze\\Parser\\Activity\\Common\\ParserInterface;\nuse Runalyze\\Parser\\Common\\FileContentAwareParserInterface;\nuse Runalyze\\Parser\\Common\\FileTypeConverterInterface;\n\nabstract class AbstractActivityParserTestCase extends \\PHPUnit_Framework_TestCase\n{\n /** @var null|ActivityDataContainer|ActivityDataContainer[] */\n protected $Container;\n\n /** @var int */\n protected $NumberOfActivities = 0;\n\n /** @var string[] */\n protected $FilesToClear = [];\n\n protected function tearDown()\n {\n foreach ($this->FilesToClear as $file) {\n if (file_exists($file)) {\n unlink($file);\n }\n }\n }\n\n /**\n * @return string\n */\n protected function pathToTestFiles()\n {\n return TESTS_ROOT.'/testfiles/';\n }\n\n /**\n * @param FileTypeConverterInterface $converter\n * @param FileContentAwareParserInterface $parser\n * @param string $file file path relative to 'testfiles/'\n * @param string[] $expectedOutputFiles\n * @param bool $completeAfterwards\n */\n protected function convertAndParseFile(FileTypeConverterInterface $converter, FileContentAwareParserInterface $parser, $file, array $expectedOutputFiles, $completeAfterwards = true)\n {\n $outputFile = $converter->convertFile($this->pathToTestFiles().$file);\n\n if (!", "is_array($outputFile)) {\n $outputFile = [$outputFile];\n }\n\n $this->FilesToClear = $outputFile;\n $path = $this->pathToTestFiles();\n $outputFile = array_map(function ($file) use ($path) {\n return str_replace($path, '', $file);\n }, $outputFile);\n\n $this->assertEquals($expectedOutputFiles, $outputFile);\n\n $this->parseFiles($parser, $outputFile, $completeAfterwards);\n }\n\n protected function parseFiles(FileContentAwareParserInterface $parser, array $files, $completeAfterwards = true)\n {\n $tmpContainer = [];\n\n foreach ($files as $currentFile) {\n $this->parseFile($parser, $currentFile, $completeAfterwards);\n\n if (!", "is_array($this->Container)) {\n $tmpContainer[] = $this->Container;\n } else {\n $tmpContainer = $tmpContainer + $this->Container;\n }\n }\n\n $this->NumberOfActivities = count($tmpContainer);\n $this->Container = 1 == $this->NumberOfActivities ? ", "$tmpContainer[0] : $tmpContainer;\n }\n\n /**\n * @param FileContentAwareParserInterface $parser\n * @param string $file file path relative to 'testfiles/'\n * @param bool $completeAfterwards\n */\n protected function parseFile(FileContentAwareParserInterface $parser, $file, $completeAfterwards = true)\n {\n $this->parseFileContent($parser, file_get_contents($this->pathToTestFiles().$file), $completeAfterwards);\n }\n\n /**\n * @param FileContentAwareParserInterface $parser\n * @param string $fileContent\n * @param bool $completeAfterwards\n */\n protected function parseFileContent(FileContentAwareParserInterface $parser, $fileContent, $completeAfterwards = true)\n {\n $parser->setFileContent($fileContent);\n $parser->parse();\n\n $this->setContainerFrom($parser, $completeAfterwards);\n }\n\n /**\n * @param ParserInterface $parser\n * @param bool $completeAfterwards\n * @param bool $runFilter\n */\n protected function setContainerFrom(ParserInterface $parser, $completeAfterwards = true, $runFilter = true)\n {\n $filterCollection = new DefaultFilterCollection();\n $this->NumberOfActivities = $parser->getNumberOfActivities();\n $this->Container = [];\n\n for ($i = 0; $i < $this->NumberOfActivities; ++$i) {\n $this->Container[] = $parser->getActivityDataContainer($i);\n\n if ($completeAfterwards) {\n $this->Container[$i]->completeContinuousData();\n }\n\n if ($runFilter) {\n $this->Container[$i]->filterActivityData($filterCollection);\n }\n\n if ($completeAfterwards) {\n $this->Container[$i]->completeActivityData();\n }\n }\n\n if (1 == $this->NumberOfActivities) {\n $this->Container = $this->Container[0];\n }\n }\n\n /**\n * @param array $expectedRounds [[duration [s], distance [km]], ...]\n * @param int $deltaDuration [s]\n * @param float $deltaDistance [km]\n */\n protected function checkExpectedRoundData(array $expectedRounds, $deltaDuration = 0, $deltaDistance = 0.0)\n {\n $this->checkExpectedRoundDataFor($this->Container, $expectedRounds, $deltaDuration, $deltaDistance);\n }\n\n /**\n * @param ActivityDataContainer $container\n * @param array $expectedRounds [[duration [s], distance [km]], ...]\n * @param int $deltaDuration [s]\n * @param float $deltaDistance [km]\n */\n protected function checkExpectedRoundDataFor(ActivityDataContainer $container, array $expectedRounds, $deltaDuration = 0, $deltaDistance = 0.0)\n {\n $this->assertEquals(count($expectedRounds), $container->Rounds->count());\n\n foreach ($expectedRounds as $i => $expectedRoundData) {\n $this->assertEquals($expectedRoundData[0], $container->Rounds[$i]->getDuration(), 'Round #'.$i.' ", "has wrong duration.', ", "$deltaDuration);\n $this->assertEquals($expectedRoundData[1], $container->Rounds[$i]->getDistance(), 'Round #'.$i.' ", "has wrong distance.', ", "$deltaDistance);\n }\n }\n\n /**\n * @param array $expectedPauses [[time index [s], duration [km](, hr start [bpm], hr end [bpm])], ...]\n * @param int $deltaDuration [s]\n */\n protected function checkExpectedPauseData(array $expectedPauses, $deltaDuration = 0)\n {\n $this->assertEquals(count($expectedPauses), $this->Container->Pauses->count());\n\n foreach ($expectedPauses as $i => $expectedPauseData) {\n $this->assertEquals($expectedPauseData[0], $this->Container->Pauses[$i]->getTimeIndex(), 'Pause #'.$i.' ", "has wrong time index.', ", "$deltaDuration);\n $this->assertEquals($expectedPauseData[1], $this->Container->Pauses[$i]->getDuration(), 'Pause #'.$i.' ", "has wrong duration.', ", "$deltaDuration);\n\n if (isset($expectedPauseData[2]) && isset($expectedPauseData[3])) {\n $this->assertEquals($expectedPauseData[2], $this->Container->Pauses[$i]->getHeartRateAtStart(), 'Pause #'.$i.' ", "has wrong heart rate at start.');", "\n $this->assertEquals($expectedPauseData[3], $this->Container->Pauses[$i]->getHeartRateAtEnd(), 'Pause #'.$i.' ", "has wrong heart rate at end.');", "\n }\n }\n }\n}\n" ]

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[ "---\nabstract: |\n We present a physical model to explain the behavior of long-term, time series measurements of chloride, a natural passive tracer, in rainfall and runoff in catchments \\[[*Kirchner et al.*]{}, [*", "Nature, 403*]{}(524), 2000\\]. ", "A spectral analysis of the data shows the chloride concentrations in rainfall to have a white noise spectrum, while in streamflow, the spectrum exhibits a fractal $1/f$ scaling. ", "The empirically derived distribution of tracer travel times $h(t)$ follows a power-law, indicating low-level contaminant delivery to streams for a very long time. ", "Our transport model is based on a continuous time random walk (CTRW) with an event time distribution governed by $\\psi(t)\\sim\n A_{\\beta}t^{-1-\\beta}$. The CTRW using this power-law $\\psi(t)$ (with $0<\\beta<1$) is interchangeable with the time-fractional advection-dispersion equation (FADE) and has accounted for the universal phenomenon of anomalous transport in a broad range of disordered and complex systems. ", "In the current application, the events can be realized as transit times on portions of the catchment network. ", "The travel time distribution is the first passage time distribution $F(t; l)$ at a distance $l$ from a pulse input (at $t=0$) at the origin. ", "We show that the empirical $h(t)$ is the catchment areal composite of $F(t; l)$ and that the fractal $1/f$ spectral response found in many catchments is an example of the larger class of transport phenomena cited above. ", "The physical basis of $\\psi(t)$, which determines $F(t; l)$, is the origin of the extremely long chemical retention times in catchments.", "\nauthor:\n- 'H. Scher'\n- 'G. Margolin'\n- 'R. Metzler'\n- 'J. Klafter'\n- 'B. Berkowitz'\ntitle: 'The dynamical foundation of fractal stream chemistry: The origin of extremely long retention times'\n---\n\nIntroduction\n============\n\nThe distribution of travel times required for chemical substances to travel through a catchment is an important hydraulic quantity, determining the retention of pollutants until they are eventually released to a stream or lake. ", "The same distribution controls the transport of chemicals in subsurface hydrological systems. ", "The nature of this distribution determines the expected ecological impact of contaminants.", "\n\nIn a long-term catchment study conducted at Plynlimon, Wales, [*Kirchner et al.*]{} ", "\\[2000\\] (hereafter denoted KFN) compare the (input) time series of the concentration $c_R(t)$ of chloride tracer in the rainfall to the (output) time series of the concentration $c_s(t)$ into the Hafren stream. ", "They relate the concentrations through the convolution integral $$\\label{conv}\nc_s(t)={\\textstyle\\int_0^\\infty}h(t')c_R(t-t')dt'$$ where the effective travel time distribution $h(t)$ governs the lag time between injection of the tracer through rainfall and outflow to the stream.", "\n\nKFN observe that the streamflow (volume of water) responds rapidly to storm rainfall inputs while the $c_s(t)$ response is highly damped (i.e., low-level contaminant delivery to streams for a very long time). ", "The timescales of catchment hydrologic and chemical response are resolved using spectral methods [@duffy] (in which the input/output response can be compared at each (time) wavelength). ", "The spectral power of the water fluxes of rainfall and streamflow coincide while the spectra of $c_s(t)$ show strong attenuation on all wavelengths less than 5-10 years. ", "Further, the $c_R(t)$ spectra scale as white noise in sharp contrast to the fractal $1/f$ scaling of the $c_s(t)$ spectra. ", "Using these results in the Fourier transform of the convolution in (\\[conv\\]), with $f$ denoting frequency, and $C_s$, $H$ and $C_R$ representing the respective Fourier transforms, $$\\label{amp}\nC_s(f)=H(f)C_R(f)$$ and the relation of the power spectra is $$\\label{power}\n|C_s(f)|^2=|H(f)|^2|C_R(f)|^2$$ Since $|C_R(f)|^2$ is nearly a white noise spectrum (a constant) one has $|H(f)|^2 \\propto |C_s(f)|^2$. From the measured power-law scaling of $|C_s(f)|^2\n\\propto f^{-0.97}$, KFN conclude that $$\\label{htail}\nh(t) \\sim t^{-m}$$ (from $H(f)\\sim f^{-(1-m)}$), where $m \\approx 0.5$.\n\nIn order to ensure that $h(t)$ is integrable and possesses a finite average travel time, KFN arbitrarily chose the gamma distribution $$\\label{tddk}\nh(t)=\\frac{t^{\\gamma-1}}{\\varrho^{\\gamma}\\Gamma(\\gamma)}\ne^{-t/\\varrho}$$ with $\\gamma=0.48$ and $\\varrho=1.9$ years, with a characteristic travel time $T_h \\equiv\\int_0^{\\infty}h(t)t dt=\\gamma\\varrho$. Due to the relatively large value of $\\varrho$, essentially the entire data correspond to the power-law $h(t)\\sim t^{\\gamma-1}$ with the power spectrum $|C_s(f)|^2 \\propto|H(f)|^2\\sim f^{-2\\gamma}$. KFN refer to similar scaling between $f^{-0.7}$ and $f^{-1.2}$ found in Scandinavian and North American field sites, which indicates a certain ubiquity to fractal, scale-free forms (which is the issue we address in this letter).", "\n\nTransport models\n================\n\nThe first step to understanding transport in the catchment is the clarification of the meaning of (\\[conv\\]). ", "The $h(t)$ is the [*effective*]{} response to a pulse of rain falling on the entire area of the catchment. ", "Every point of this area is a source of chloride and the stream is a line sink for the chloride. ", "We simplify the area to be a rectangle of width $\\lambda$ about this stream sink (with periodic boundary conditions on the sides perpendicular to the stream[@ctrw]). ", "The sink or absorbing boundary ensures the correct “counting rate\" of chloride at the arriving point, i.e., the first passage time distribution $F(t;l)$ is the appropriate travel time distribution from a pulse source at point $l$. In terms of this [*intrinsic*]{} distribution, $$\\label{eq:gen}\nc_{s}(t;l_s) = \\int_0^\\infty \\sum_{l\\in \\Omega}F(t';l-l_s) c_{R}\n(t-t';l)dt'$$ where $c_{s}(t;l_s)$ is the chloride concentration at the stream position $l_s$ at time $t$, $\\Omega$ is the size of the catchment and $c_{R}(t;l)$ the rain-input at a position $l$ in $\\Omega$. We can consider the sampling positions $\\{l_s \\}$ of $c_{s}$ to be a small region compared to $\\Omega$ and hence $c_{s}(t;l_s) \\approx\nc_{s}(t)$. To do the $l$-sum we assume that the rainfall is distributed uniformly in $\\Omega$, $c_{R}(t;l) \\approx\nc_{R}(t)$. Hence, we recover (\\[conv\\]) now with $$\\label{eff}\nh(t) \\equiv \\sum_{l\\in \\Omega}F(t;l)$$ The distribution $F(t;l)$ must be integrable in time and thus so $h(t)$ for a finite $\\Omega$. The basis of comparison for various transport approaches is the computation in (\\[eff\\]).", "\n\nAdvection-dispersion equation (ADE)\n-----------------------------------\n\nThe textbook approach to transport of passive tracers in both surface and subsurface systems usually focuses on the advection-dispersion equation (ADE) $$\\label{dae}\n\\partial {\\cal W}/\\partial t+v\\partial {\\cal W}/\\partial x=D\\partial^2 {\\cal\nW}/\\partial x^2$$ e.g., for 1d with constant $v$ the average fluid velocity and $D$ the dispersion coefficient. ", "This equation governs the temporal evolution of the probability density function (pdf) ${\\cal W}(x,t)$ of finding a tracer particle, which undergoes dispersive motion, at a certain position $x$ at time $t$ after release at $t=0$. The pdf ${\\cal W}$ is the normalized concentration profile.", "\n\nThe travel time distribution belonging to (\\[dae\\]) can be obtained by the Laplace Transform ($LT$) technique. ", "This yields the $LT$ $\\tilde{{\\cal F}}(u;x)\\equiv\\int_0^{\\infty}{\\cal F}(t;x)e^{-ut}dt$ of the first passage time from $x$ to the absorbing boundary at $x=0$, $\\tilde{{\\cal F}}(u;x)=\n\\exp\\left(x\\left[v-\\sqrt{4Du+v^2}\\right]/(2D)\\right)$. $LT$ inversion delivers the travel time distribution \\[gauss\\] [F]{}(t;x) = () which when inserted for $F(t;x)$ in (\\[eff\\]) yields $$\\begin{aligned}\n\\label{int}\nh(t) \\! \\! \\! \\! &", "\\propto& \\! \\! \\! \\! ", "\\int_0^\\lambda {\\cal F}(t;x)dx =\\frac\n{v}{2}\\bigl[{\\rm erf}(z) +{\\rm erf}\\left(\\frac {P_e}{4z}-z \\right) \n\\nonumber \\\\&+&\n\\! \\! \\! \\! ", "\\frac {\\exp(-z^2)-\\exp\\left(-(\\frac\n{P_e}{4z}-z)^{2}\\right)}{\\sqrt{\\pi}z}\\bigr]\\end{aligned}$$ where the Peclet number $P_e\\equiv \\lambda v/D$, $z \\equiv \\frac {1}{2}\\sqrt{v^{2}t/D}$ and erf$(z)$ is the error function (the same result (\\[int\\]) was also derived in [*Kirchner et al.*]{}, ", "2001). ", "For $t<0.1 D/v^2$, $h(t)\\sim t^{-\\frac{1}{2}}$ which is similar to (\\[htail\\]) for $m\n\\approx 0.5$. \\[This upper limit on the time range holds for $P_e\\ge1$; for $P_e<1$ the limit is smaller.\\] The range is estimated by assuming $D$ to be the macrodispersion, $D=v\\alpha$, where $\\alpha$ is the dispersivity. ", "Assuming $v\\approx 10^2$ m/yr and on the km scale $\\alpha \\sim (1-10^2)$ m, $t<0.1\\alpha/v \\sim (10^{-3}-10^{-1})$ yr. ", "One needs $v\\approx 10$ m/yr and $\\alpha\n\\sim 10^2$ m in (\\[int\\]), for $h(t) \\sim t^{-\\frac{1}{2}}$ to partially overlap the time range of observation of this dependence [@kirchner]. ", "Moreover, this behavior is only the same as (\\[htail\\]) in the special case where $m$ (or $\\gamma$) = $\\frac {1}{2}$. The catchment data (spectral power $\\sim \nf^{-2\\gamma}$) quoted above cover a range of $0.7\\leq 2\\gamma\\leq 1.2$.\n\nFor large $t$, $h(t)$ in (\\[int\\]) exhibits an exponential decrease $\\sim t^{-\\frac{3}{2}}$ $\\exp\\left(-v^2(4D)^{-1}t\\right)$ which is faster than (\\[tddk\\]). ", "The decrease in $h(t)$ at large $t$ ($t>>\\lambda/v$) is due to the finite size of the catchment and not an arbitrary limiting time. ", "The relation between the operative time range of (\\[htail\\]) and $\\lambda$ will be determined in the following.", "\n\nContinuous-time random walk and time-fractional-ADE\n---------------------------------------------------\n\nAs shown above the standard treatment of the transport using the ADE yields a marginal accounting of the data. ", "A transport model must determine a $F(t;l)$ that when inserted in (\\[eff\\]) gives rise to (\\[htail\\]) for over three decades of time [@kirchner]. ", "As we will show this is best expedited with a non-Gaussian form of $F(t;l)$. A particularly dispersive form of $F(t;l)$ is associated with anomalous transport which has been observed in a wide range of disordered and complex systems: electron hopping/multiple-trapping in amorphous semiconductors [@ctrw], particle migration in fracture networks [@till], contaminant transport in heterogeneous porous media [@bescher], anomalous diffusion[@report], and Hamiltonian chaos[@pt]. ", "There are key common features in these anomalous transport phenomena, e.g., non-Gaussian propagation of an initial pulse of particles with a mean position $\\ell(t)$ and standard deviation $\\sigma(t)$ exhibiting the same sublinear dependence on $t$ (in the presence of a bias or head). ", "A continuous time random walk (CTRW) transport process has successfully accounted for these unusual basic features. ", "The anomalous behavior is an outcome of a CTRW governed by a long-tail distribution of the individual transition times or event times (which have to be defined in each physical context, e.g., trap release), $$\\label{psi}\n\\psi(t)\\sim A_{\\beta}t^{-1-\\beta}$$ where $A_{\\beta}$ is a constant. ", "Over the observation time range in which (\\[psi\\]) obtains we have for the propagating plume $P(l,t)$ $$\\ell (t) \\sim t^\\beta, \\qquad\\sigma(t) \\sim t^\\beta\\qquad0<\\beta<1$$ The highly dispersive nature of this $P(l,t)$ can be discerned by the ratio $\\sigma(t)/\\ell (t)\\sim$ constant, instead of the familiar $1/\\sqrt{t}$ for a Gaussian plume. ", "The latter is produced for $\\beta>2$ (while for $1<\\beta<2$ one has an intermediate $t$-dependence).", "\n\nThe CTRW accounts naturally for the cumulative effects of a sequence of transitions which constitutes the particle transport. ", "The formalism of the CTRW has been well documented in the literature \\[[*Berkowitz and Scher*]{}, 1998; [*Metzler and Klafter*]{}, 2000\\]. ", "For brevity we show the key equation for our purpose here in Laplace space (for three dimensions) $$\\label{1stP}\n\\tilde{F}({\\bf s},u)=\\tilde{P}({\\bf s},u)/\\tilde{P}(0,u) \\qquad\n\\qquad {\\bf s} \\ne 0$$ where the particle starts at the origin at $t=0^+$, $\\tilde{P}({\\bf\ns},u)$ is the $LT$ of $P({\\bf s},t)$, the probability density to find the particle on ${\\bf s}$ at time $t$ (plume), and $\\tilde{F}({\\bf s},u)$ is the $LT$ of $F({\\bf s},t)$, the probability per time for the particle to first arrive at ${\\bf s}$ at time $t$.\n\nExplicit evaluations for $\\tilde{F}({\\bf s},u)$ have been determined for symmetric situations (e.g., plane (line) source to plane (line) sink) and with the use of (\\[psi\\]) [@ctrw]. ", "The symmetric cases allow a reduction of the problem to a one-dimensional form of $F$ which we write as $F(t; x)$ and $$\\label{ltF}\n\\tilde{F}(u;x)=\\exp(-xu^{\\beta}/\\bar{l}) \\qquad(0<\\beta<1)$$ ($u$ dimensionless). ", "The inverse $LT$ of $\\tilde{F}(u;x)$ has been expressed in terms of a class of Fox $H$-functions [@report], but it is more expedient to work directly with (\\[ltF\\]) in the evaluation of $h(t)$, which will be considered in the next section.", "\n\nMathematically, the CTRW (in the special case using (\\[psi\\]) and $(0<\\beta<1)$) is interchangeable with the time-fractional advection-dispersion equation (FADE) [@report] $$\\label{fda}\n\\frac{\\partial W}{\\partial t}=\\, _0D_t^{1-\\beta}\\left(-v_{\\beta}\n\\frac{\\partial}{\\partial x}+d_{\\beta}\\frac{\\partial^2}{\\partial x^2}\n\\right)W(x,t)$$ where the Riemann-Liouville operator is defined in terms of the convolution [@report], $$\\label{rl}\n_0D_t^{1-\\beta}W(x,t)=\\frac{1}{\\Gamma(\\beta)}\\frac{d}{dt}\\int_0^tdt'\n\\frac{W(x,t')}{(t-t')^{1-\\beta}},\\, 0<\\beta<1.$$ The form of FADE (\\[fda\\]) is the natural generalization of the ADE (\\[dae\\]) for power-law forms of $\\psi$. The solutions of FADE reproduce those of the CTRW in this special case, and in the spatial continuum limit they form a natural bridge between the CTRW and the ADE [@tipm].", "\n\nLong Retention Times\n====================\n\nWe proceed to insert (\\[ltF\\]) into the $LT$ of (\\[eff\\]) to obtain $$\\label{eq:lth}\n\\tilde{h}(u) \\propto \\int_0^\\lambda\n\\exp(-lu^{\\beta}/\\bar{l})dl=\\bar{l}u^{-\\beta}(1-\\exp(-\\lambda\nu^{\\beta}/\\bar{l}))$$ where $\\bar{l}$ is the mean step distance. ", "The expression for $\\tilde{h}(u)$ in (\\[eq:lth\\]) has been thoroughly studied in another context [@ctrw]; the main features are $$h(\\tau)\\sim\\left\\{\\begin{array}{ll}\n\\tau^{\\beta-1}, & \\tau<\\tau^*\\\\\n\\tau^{-\\beta-1}, & \\tau>\\tau^*\n\\end{array}\\right.", "\n\\label{scaling}$$ ($\\tau$ dimensionless time). ", "The exponent for $\\tau>\\tau^*$ ensures that $h(\\tau)$ is integrable. ", "On a log-log plot $h(\\tau)$ is two constant slopes, $\\beta-1$, $-1-\\beta$, with a turnover range between them. ", "The center time of this range, $\\tau^*$, can be estimated as the time for the argument of the exponent in (\\[eq:lth\\]) to be $\\sim\nO(1)$ (using $u \\sim 1/\\tau$) $$\\label{tau}\n\\tau^{*} \\sim (\\frac {1-\\beta}{\\beta})^{\\frac {1-\\beta}{\\beta}}(\\beta\n\\lambda/\\bar{l})^{\\frac {1}{\\beta}}$$ (The $\\beta$-factors derive from a more detailed analysis \\[[*Scher and Montroll*]{}, 1975, Appendix C\\].) ", "For $\\beta =\\frac{1}{2}$, in (\\[eq:lth\\]) one can do the inverse $LT$ and obtain $h(\\tau) \\sim (\\pi\n\\tau)^{-\\frac{1}{2}}(1-\\exp(-\\lambda^2 /4\n\\bar{l}^2 \\tau))$, clearly showing (\\[scaling\\])-(\\[tau\\]).", "\n\nThe change from $\\tau$ to $t$ is model dependent (to be discussed below). ", "We use $\\tau = v_ot/\\bar{l}\\varepsilon$, where $v_o$ is a characteristic velocity (of the velocity distribution) and $\\varepsilon$ is a constant. ", "For $\\beta = \\frac{1}{2}$, $v_o \\sim$ 100 m/yr, $\\lambda \\sim \\frac{1}{2}$ km, $\\bar{l} \\sim$ 30 m and $\\varepsilon \\sim \\frac{1}{2}$, one has (from (\\[tau\\]) with $\\tau^* = v_ot^*/\\bar{l}\\varepsilon$), $t^* \\sim$ 10 yr, which is a reasonable time scale for the change from $h(t) \\sim t^{\\beta-1}$. Hence, our scaling result (\\[scaling\\]) agrees with the KFN data (\\[htail\\]) over the measurement time range ($>$ 3 decades for t$\\le$ 10 yrs) with $\\beta=\\gamma$ ($\\equiv 1-m$). ", "The $t$-“cutoff\" for $h(t)$ in (\\[scaling\\]) is algebraic, $t^{-\\beta-1}$, not exponential as in (\\[tddk\\])! ", "This behavior of $h(t)$ is indicative of extremely long chemical retention times in catchments. ", "The turnover to the $t^{-\\beta-1}$ dependence (in (\\[scaling\\])) is a prediction of the CTRW theory and has not yet been observed. ", "A finite value of $T_h$ depends on a change in the behavior of (\\[psi\\]). ", "For $t\n\\gg t^*$, the tail of $\\psi(t)$ becomes steeper and for $\\beta>2$, the [*intrinsic*]{} arrival time distribution evolves to ${\\cal F}(t;x)$.\n\nIndependent tests of our transport model can be obtained with experiments using a different tracer (d) and boundary conditions. ", "For injection of the tracer d at various catchment points $\\{ {\\bf x}\n\\}$, the concentration in the stream $c_{d}(t;{\\bf l_s})$ is proportional to $F({\\bf\nx}-{\\bf l_s},t)$, determined for these boundary conditions. ", "\\[This result answers the question raised by [*Stark and Stieglitz*]{} \\[2000\\] about a site-specific spill.\\] This is also a method for obtaining a value of $\\beta$, which determines the shape of $F({\\bf x},t)$.\n\nThere are many different physical mechanisms (cf. ", "Refs. ", "above) that can give rise to the $\\psi(t)$ in (\\[psi\\]) that has generated our results for $h(t)$. The common features are the representation of the transport process as a series of transitions \\[[*Berkowitz and Scher*]{}, 1998, 2001\\] and the encounter within this series of a sufficient number of transition-times that are much larger than the median one. ", "These relatively few long-time events, which can be due to release from traps/stagnant-regions and/or passage through low velocity segments, can have a dominant influence on the overall transport. ", "The relative weighting of these events is expressed by the exponent of the power-law in (\\[psi\\]).", "\n\nThe hydrologic environments beneath the catchment subregions can contain a sufficient number of these low velocity sections and stagnant dead-ends. ", "The local slope (and interconnection [@rinaldo]) of the catchment side-channels also affects the velocity distribution. ", "The subsurface of the catchment basin can be modeled as a heterogeneous porous medium and/or a random fracture network [@bescher]. ", "In the latter the fragment-length distribution, $f(s)$, and the fragment-velocity histogram, $\\Phi({\\bf \\xi})$, are mapped onto the probability rate for a transit time t (through a fragment) with a displacement [**s**]{}, ([**s**]{},t) ([****]{})f(s) where $|{\\bf \\xi}|=1/v$, $\\hat{\\bf \\xi}=\\hat{\\bf v}$, $t=s\\xi$ and $\\psi (t) \\equiv \\sum_s \\psi ({\\bf s},t)$. The anomalous transport observed in the fracture network particle tracking simulations is due to the power-law tail of $\\Phi({\\bf \\xi}) \\rightarrow \\xi^{-1-\\beta}$ at large $\\xi$. This is the expected behavior to be found in the catchment subsurface $\\Phi_c({\\bf \\xi})$ distribution because this hydrologic environment is the same as ones modeled successfully by the CTRW theory \\[[*Berkowitz and Scher*]{}, 1998, 2001\\]. ", "The experiments outlined above can test these properties.", "\n\nConclusion\n==========\n\nIn this letter we introduce the phenomenon of anomalous transport into an analysis of the comparison of the power spectra of the time series of chloride in rainfall and in (stream) runoff. ", "An [*effective*]{} distribution of travel times $h(t)$ is derived (by KFN from the data) which we show is composed of the summation from all sites of the source distribution $F({\\bf s},t)$ in the catchment. ", "The latter, in turn, is composed of a sequence of transitions governed by a power-law (tail) distribution (\\[psi\\]). ", "The results agree naturally with the data reported from a number of catchment studies, in the sense of a power-law scaling of $h(t)$ over decades of $t$ in the observational time range (using reasonable parameters). ", "A consequence of our transport model is a power-law “cutoff” of $h(t)$ predicting extremely long chemical retention times with subsequent impact on the long-term effects of contaminants on these ecosystems.", "\n\nWe thank James W. Kirchner and Colin Stark for a critical reading of the manuscript. ", "RM acknowledges the DFG and the European Commission within the Emmy Noether and SISITOMAS programmes, and BB acknowledges the European Commission (Contract EVK1-CT-2000-00062), for financial support.", "\n\nBerkowitz, B., and H. Scher, Theory of anomalous chemical transport in fracture networks, [*Phys. ", "Rev. E*]{}, [*57*]{}(5), 5858-5869, 1998.", "\n\nBerkowitz, B., and H. Scher, The role of probabilistic approaches to transport theory in heterogeneous media, [*Transp. ", "Porous Media*]{}, [*42*]{}(1-2), 241-263, 2001.", "\n\nDuffy, C. J., and L. W. Gelhar, A frequency domain approach to water quality modeling in groundwater: Theory, [*Wat. ", "Resour. ", "Res.*]{}, [*", "21*]{}(8), 1175-1184, 1985.", "\n\nKirchner, J. W., X. Feng and C. Neal, Fractal stream chemistry and its implications for contaminant transport in catchments, [*Nature, 403*]{}, 524-527, 2000.", "\n\nKirchner, J. W., X. Feng and C. Neal, Catchment-scale advection and dispersion as a mechanism for fractal scaling in stream tracer concentrations, [*J. Hydrol., ", "254*]{}, 82-101, 2001.", "\n\nKlafter, J., M. F. Shlesinger, and G. Zumofen, Beyond Brownian motion, [*Phys. ", "Today, 49*]{}(2), 33-39, 1996.", "\n\nKosakowski, G., B. Berkowitz and H. Scher, Analysis of field observations of tracer transport in a fractured till, [*J. Contam. ", "Hydrol.*]{}, [*", "47*]{}, 29-51, 2001.", "\n\nMetzler, R., and J. Klafter, The random walk’s guide to anomalous diffusion: A fractional dynamics approach, [*Phys. ", "Rep.*]{}, [*339*]{}(1), 1-77, 2000 (and refs. ", "therein).", "\n\nRodriguez-Iturbe, I., and A. Rinaldo, [*Fractal River Basins: Chance and Self-Organization*]{}, Cambridge Univ. ", "Press, New York, 1997.", "\n\nScher, H., and E. W. Montroll, Anomalous transit-time dispersion in amorphous solids, [*Phys. ", "Rev. B*]{}, [*12*]{}(6), 2455-2477, 1975.", "\n\nStark, C. P., and M. Stieglitz, The sting in a fractal tail, [*Nature*]{}, [*403*]{}, 493-495, 2000.", "\n" ]

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[ "[Undifferentiated pleomorphic sarcoma detected in the descending colon: report of a case].", "\nUndifferentiated pleomorphic sarcoma was a well-known tumor that usually involves the soft tissues. ", "However, in the alimentary tract, it was seldom reported. ", "A 55-year-old man was admitted to our hospital with lower abdominal pain. ", "Endoscopic examination showed a protruding tumor occupied the lumen of the descending colon. ", "Because of the colon obstruction by the tumor, a left hemicolectomy with en bloc lymph node dissection was performed. ", "Main occupied lesion of the tumor was mesenterium and submucosa, with no epithelial dysplasia. ", "Also, dissemination of the tumor was recognized in the mesenterium and greater omentum. ", "Based on histological and immunohistological studies, the tumor was diagnosed as undifferentiated pleomorphic sarcoma." ]

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[ "Both shortening and its classier cousin, margarine, took off for obvious reasons—who wouldn’t want a butter substitute that was cheaper, lasted longer, and came with free cookbooks? (", "All the recipes called for Crisco, of course.)", "\n\nSensing competition, dairy farmers convinced several states to stop allowing the more appetizing-looking, yellow-colored margarine in the early 20th century, but the bans were largely repealed by the late 1950s, and the golden-hued spread once again became the norm.", "\n\nA 1961 Time magazine article railed against the dangers of saturated fat (the kind found in butter and lard), and eventually some consumers began to view margarine and shortening as healthier alternatives.", "\n\nOddly, some health groups also trumpeted hydrogenated oil's benefits.", "\n\nIn the 1980s, some scientists began to associate heart disease with saturated fats, and in response, groups such as the Center for Science in the Public Interest and the National Heart Savers Association (NHSA) began to hound manufacturers for “poisoning America ... by using saturated fats,” and as a result “nearly all targeted firms responded by replacing saturated fats with trans fats,” as David Schleifer wrote in 2012 for the journal Technology and Culture.", "\n\nAt the time, many restaurants used beef fat for frying, which groups like CSPI believed was far worse than hydrogenated oils, based on the research of the time. ", "Schleifer writes:\n\n[CSPI’S 1986] Fast-Food Guide specifically criticized Taco Bell, Arby’s, Hardee’s, and Wendy’s for frying in beef fat and tropical oils (that is, coconut and palm oils). ", "But it praised Burger King for switching to vegetable shortening in 1986, which it described as “a great boon to Americans’ arteries.” ", "The guide also praised KFC, writing that the chain was “fortunately” frying in “partially saturated soybean oil . . . ", "that is much less saturated than beef fat.”", "\n\nTwo years later, the same group released the report Saturated Fat Attack, which described trans fats as “more healthful” than saturated fats, Schleifer wrote.", "\n\nIn 1990, a New York Times food writer said CSPI’s campaign prompted fast-food chains to “slim down” by switching to frying in shortening.", "\n\n***\n\nIn the 1990s, the health risks of trans fats began to eclipse those of the saturated variety. ", "A 1990 New England Journal of Medicine found that they raised “bad” cholesterol levels. ", "A 1993 Harvard study found that eating partially hydrogenated vegetable oils increased the risk of heart attacks. ", "Today, it’s estimated that trans fats contribute to thousands of early deaths each year.", "\n\nThe food industry even funded its own study with the goal of proving that trans fats were perfectly safe. ", "However, it only confirmed the earlier findings, and food manufacturers quickly began developing alternatives to hydrogenated oils. ", "Today, even Crisco has changed its recipe, and it now has less that half a gram of trans fat per serving. ", "Which means zero, if you use FDA-label math.", "\n\nSurprisingly, it was the same organization, CSPI, that later urged the FDA to add trans fats to food labels, and nutrition panels have been required to list the substance since 2006. ", "Though American consumption of trans fat has declined precipitously in recent years, it's still common in food such as microwave popcorn, margarine, and some coffee creamers. ", "But probably not for much longer." ]

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[ "Four-quadrant gate\n\nA four-quadrant gate is a type of boom barrier gate protecting a grade crossing.", "\nIt has a gate mechanism on both sides of the tracks for both directions of automotive traffic. ", "The exit gates blocking the road leading away from the tracks in this application are equipped with a delay, and begin their descent to their horizontal position several seconds after the entrance gates do, so as to avoid trapping highway vehicles on the crossing.", "\nMany people consider four-quadrant gates to be safer than two-quadrant gates because they prevent drivers from illegally driving their vehicles around lowered gates to try to beat a train.", "\n\nIn the UK, such crossings are categorised as 'Manually Controlled Barriers' (MCB) because they are always manually controlled, usually from a signal box. ", "Some are known as MCB-CCTV level crossings, because they are supervised by video link to the signal box from which they are remotely controlled.", "\n\nThe first four-quadrant gate in the United States was installed in 1952. ", "They have become common for new installations and replacements since. ", "Unlike the UK, many are automated by the rail line's signal system. ", "The first quad gate installation in the country with sensors to detect vehicles stopped in the tracks was installed in Groton, Connecticut in 1998. ", "Eight of the eleven remaining grade crossings on the Northeast Corridor now have such setups.", "\n\nReferences\n\nCategory:Level crossings\nCategory:Protective barriers\nCategory:Road infrastructure\nCategory:Street furniture\n\nFurther reading" ]

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[ "Introduction\n============\n\nClinical teaching in is an important part of nursing education ([@B1]). ", "Understanding the factors that influence the quality and quantity of clinical education is helpful in solving the related problems ([@B2]). ", "Nurses are repeatedly exposed to situations that may cause them to suffer and reduce their ability to serve the patients ([@B3]). ", "Therefore, assessment of clinical skills by undergraduate nursing programmers is important to be considered ([@B4]). ", "The importance of clinical nursing education is undeniable in personal, professional and clinical skills development ([@B5]). ", "Through nursing education, nursing students will be able to obtain necessary knowledge and skills to assist public health ([@B6]). ", "Success in this subject requires the adoption of effective approaches to familiarize the students with new knowledge and essential needs of the clients ([@B7]). ", "The existing clinical education does not meet the clinical skills competence of the students. ", "Because of the large gap between theoretical and clinical nursing education, recognition of clinical education problems is important ([@B5], [@B8], [@B9]). ", " Due to their immediate attendance in this process, the students are the best and most reliable sources for detection of these problems ([@B10]). ", "Some studies have proposed the clinical education challenges from the students' perception, such as uunavailability of qualified instructors, lack of sufficient facilities, lack of cooperation of the staff in clinical education, lack of procedures to be practiced by students, lack of clinical education tasks, mismatch between objectives and the content of clinical education curriculum, lack of acquisition of prerequisites before entering the clinical fields, lack of appropriate opportunities for learning, lack of motivation among students, knowledge deficit about the profession, implementation of learned objectives in clinical setting , students\\' lack of awareness about the objectives and evaluation methods ([@B11]-[@B15]). ", "Given the central role of students in clinical education, understanding their attitude toward the implementation of this method of education is necessary. ", "To obtain a reliable finding, this multicenter research was conducted with special focus on perceptions of clinical education among senior nursing students.", "\n\nMethods\n=======\n\nThis is a descriptive cross-sectional study aiming to determine the nursing students' perspectives on clinical education (2012-2013). ", "Stratified sampling was done on bachelor nursing students who entered the clinical environment. ", "The samples were selected from each school (Tehran University of Medical Sciences, Islamic Azad University, Baqiyatallah University of Medical Sciences, Army University of Medical Sciences, Shahed University, Shahid Beheshti University of Medical Sciences). ", "After a pilot study on 15 students, by taking the mean of 11.21, standard deviation of 1.72 and a maximum sampling error (d=0.02), 150 students were selected. ", "Data collection instrument included a researcher made questionnaire consisting of 31 questions in Likert style ranking (yes, somewhat, and no) in five domains: objectives and curriculum, clinical instructor, how to deal with students in clinical settings, supervision and evaluation. ", "Content and face validity was evaluated and confirmed by 10 nursing faculty academic members. ", "Cronbach\\'s alpha =93% was obtained for 20% of the samples. ", "Between the two phases of questionnaire completion, the interclass correlation coefficient (ICC) was 0.556. ", "All ethical issues including  obtaining the approval of research council of  Shahed University, introducing the researcher to the subjects, allowing voluntary participation, and informing the students about the research objectiveswere considered. ", "Also, the participants were assured that all the information would be confidential. ", "To identify clinical education status, the percentages of negative and positive percpectives were extracted. ", "The mean and standard deviation of each domain of the questionnaire was calculated. ", "Chi-square test was used to compare the clinical education for nursing students' perspective according to their socio-demographic characteristics (age, gender, work experience in the clinical settings and the working time). ", "Non-parametric tests (Mann-Whitney and Kruskal-Wallis) were used to compare the level of students\\' perspectives on clinical education in each of the domains. ", "The statistical analysis was performed through SPSS 14 ( SPSS Inc, Chicago ,IL ,USA). ", "The significance level for analyses was set at α=5.", "\n\nResults\n=======\n\nThe mean age of the students was 21.7±1.68 years (range: 19-28 years). ", "66% (n=97) of them were male. ", "Among the students, 30.1% (n=44) had an experience of student work in hospital. ", "The mean work time was 3.58 ± 0.48 months. ", "In the domain of clinical educational objectives, the most positive scores (agreement) were related to \\\"presenting job description to the student \\\" and \\\"providing clinical education objectives on the first day of education\\\" with 54% of responses for each item, and the lowest score (disagreement) were \\\"Coordination between educational objectives and expectations of staff from students \\\" belonged to 33.6% of responses. ", "The mean percentage of positive responses (agree view) was in the domain of educational objectives (44.24%) and for negative responses (opposing views) it was 22.41%. ", "In domain of instructor, the most score (agree views) was \\\"expectation of clinical instructor to students' on time attendance at the field\\\"(74.5%) and the lowest score (opposing views) belonged to \\\"clinical instructor in dealing with the problem reduces the students' stress \\\"(22.1%). ", "In domain of clinical instructor, 79.53% of responses were positive (agree views) and 18.5% negative (opposing views). ", "In domain of interaction with students, the most score (agree views) was related to\\\" strengthen the self-assurance of students by the instructor and staff\\\" (46.6%) and the lowest score (opposing view) was given to \\\"empowering the students to make decisions in patient care planning \\\"(25.7%). ", "In domain of interaction with students, 39.75% of the responses were positive (agree views) and 22.53% negative (opposing views). ", "In domain of clinical environment, the most score (agree views) was related to \\\"sufficient number of patients for learning\\\" (45.9%) and the lowest one (opposing views view) belonged to \\\"motivation for occupation through clinical environment\\\" (72.2%). ", "In domain of clinical environment, 35.3% of responses were positive (agree views) and 33.66% negative (opposing views). ", "The most positive responses (agree views) was related to clinical instructor (81.5%) and the most negative ones (opposing views) to clinical environment (33.66%) ([Table 1](#T1){ref-type=\"table\"}).", "\n\n###### \n\nThe students\\' perspective about clinical education domains\n\n --------------------------------------------------------------------------------------------\n **Domains of clinical education** Positive responses\\ Negative responses\\\n N (%) N (%) \n ------------------------------------------------ --------------------- ---------------------\n Education objectives 114 (77.59%) 36 (22.41%)\n\n Instructor 123 (81.50%) 27 (18.50%)\n\n How to deal with students in clinical settings 117 (77.47%) 33 (22.53%)\n\n Clinical environment 114 (66.34%) 36 (33.66%)\n\n Evaluation and supervision 116 (76.85%) 34 (23.15%)\n --------------------------------------------------------------------------------------------\n\nMale and female students had different perspectives in learning objectives (p=0.001), instructor (p=0.046), how to deal with students in clinical settings (p=0.005), clinical environment (p=0.001), evaluation and supervision (p=0.005). ", "Also, male students were more positive than females in all domains of clinical education. ", "The perspective of clinical education did not differ by age or work experience. ", "But, nursing students had differ perspective on educational objectives, (p=0.039), monitoring/evaluation (p\\<0.001), and interacting with students (p=0.032) according to the duration of their work. ", "The mean of supervision and evaluation decreased with increase in the work experience (p=0.002) ([Table 2](#T2){ref-type=\"table\"}).", "\n\n###### \n\nThe students\\' perspective of clinical education domains by gender and work years\n\n **Domains of clinical education** **Gender** **Mean rank** ***p***\n ------------------------------------------------ ------------ --------------- ---------\n Learning objectives Male 79.75 0.001\n Female 56.17 \n Instructor Male 75.82 0.046\n Female 61.35 \n How to deal with students in clinical settings Male 79.86 0.005\n Female 59.15 \n Clinical environment Male 79.09 0.001\n Female 54.29 \n Evaluation and supervision Male 79.15 0.005\n Female 59.60 \n Evaluation and supervision \\<6 month 60.96 0.002\n 6-12 month 43.78 \n \\>12 month 38.97 \n\nDiscussion\n==========\n\nFindings showed that most students believed that tasks and objectives are presented at the beginning of clinical education. ", "However, there were low ratings to educational objectives and staff expectations of students; it means a challenge or an obstacle in these items. ", "Accordingly, in Delaram's study (2013), students have outlined discrepancy between the staff expectations and objectives of clinical education ([@B15]).", "\n\nSimilarly, in Khadivzadeh's research (2004), most of the students considered the clinical education objectives as clear and consistent with the content of clinical education ([@B16]). ", "In contrast to our findings, Taghinejad (2008), Zaighami (2004) and Ebrahami (2004) stated that nursing students have considered the lack of clear job description and inappropriateness clinical education with objectives as the major problems in clinical education ([@B5], [@B11], [@B12]). ", "In the instructor domain, the most positive responses were related to instructor expectation of timely students' attendance at clinical field and the most negative responses belonged to the ability to reduce the students' stress in dealing with problems. ", "Similarly, Delaram (2013) suggest students' timely attendance as the strengths of clinical education from the students' perspective ([@B15]).", "\n\nIn some studies, different opinions are presented about the clinical instructor characteristics. ", "For example, in the study conducted by Ebrahimi (2004) the lack of support and insufficient justification for nursing profession were clinical education barriers related to the instructor ([@B12]). ", "Gignac-Caille (2002) showed that the students\\' interpersonal relationships as the clinical capabilities can be effective in the performance of clinical instructors ([@B17]). ", "The findings of this study showed that most of the students responded c appropriately with the instructor and were supported to increase the ability for dealing with stress in clinical practice. ", "But, Tavakoli Ghochani (2009) in determining the characteristics of an effective clinical instructor revealed that the students had given lower scores to interpersonal interaction by the instructor ([@B18]).", "\n\nFakhr Movahedi's in his study (2013) showed that nursing students scored the clinical instructors' behaviors above average ([@B1]). ", "In domain of \"how to deal with students in the clinical environment\", most of the students responded positively to reinforcing self-assurance by the instructor and staff and the most negative responses were given to authority to make decisions to planning patient care. ", "Similar to this finding, Delaram (2013) showed students are not authorized to make decisions in patient care at clinical education ([@B15]). ", "Also, Mohammadi (2004) described the most important problems as the lack of cooperation and improper communication with students in clinical education ([@B19]).", "\n\nAccordingly, \"sufficient number of patients for learning\" was the strength and \"effectiveness of motivation for future jobs\" was at a disadvantage from the nursing students' perspective. ", "In other studies, the lack of the necessary educational aids, great number of students and forcing students to perform the duties of the staff, the lack of adequate facilities, lack of possible implementation learned items in clinical environment were the most negative points from the nursing students' perspective ([@B16], [@B19], [@B20]). ", "Henderson (2006) investigated the students\\' perception of the psycho-social clinical learning environment and showed that the stable clinical environment can support further learning and impart more knowledge to students in clinical education ([@B21]).", "\n\nPayne and Glaspie (2013) found that students\\' performance is not influenced by the perception of the clinical learning environment. ", "In other words, a well-accepted clinical education environment may not have significant effect on the student outcomes ([@B22]). ", "O\\'Mara (2013) studied the nursing students\\' experiences of challenges related to the clinical learning environment. ", "Nursing students perceived these challenges in relation to clinical environment and learning experiences, so it has affected their learning opportunities and professional identity ([@B23]).", "\n\nAccording to the findings, the least ratings were monitoring and evaluation (complete supervision on clinical education and giving information on how to evaluate at the first session of education), respectively. ", "Consistent with this result, in Baraz's study (2008) clinical evaluation from the nursing students' perspective was weak ([@B24]). ", "One of the objectives of this study was to investigate the relationship between students' work experience and their perception of monitoring and evaluation in clinical education. ", "So, by increasing of students' work experience, there was more negative perception to monitoring and evaluation. ", "This could be due to increasing clinical experience, more formal interactions with other nurses, and ongoing assessment by superiors such as nursing supervisors in their work place. ", "The other finding was the difference between male and female nursing students' perceptions on clinical education. ", "However, the gender differences and its related reasons in how students perceive the clinical education issues should be studied carefully in future research.", "\n\nOne of the limitations of this study is that only students from Tehran university nursing school were studied. ", "So, generalization of the findings should be made with caution. ", "Also, the conservative responses to questions could affect the accuracy of the results. ", "In any case, by creating appropriate conditions for responding to the questionnaire and using non-parametric methods, this limitation was reduced.", "\n\nConclusion\n==========\n\nClinical education is a very complex process and involves many different dimensions. ", "Given the influence of nursing education on the community health, provision of facilities and revising in evaluation systems of students is recommended. ", "In the present study, there was an attempt to determine the most important barriers and strengths of clinical education from the students' perspective. ", "In this regard, particular topics in the area of instructor had been confirmed by students. ", "However, the domains of clinical environment, monitoring and evaluation did not show a favorable condition from the students' perception.", "\n\nThis study describes the issues related to nursing students\\' perceptions of clinical education. ", "Therefore, determining the students\\' perspectives can improve the quality of nursing clinical education. ", "It is recommended that studies on nursing students' perspectives in the years of their academic education (from entering clinical education until graduation) should be conducted using cross-sectional or longitudinal methods and compared with postgraduate period.", "\n\nThis study was approved by the research council of Shahed University (Code: 117/152662/9102). ", "The authors appreciate all nursing students and colleagues for their help in this project.", "\n\n**Conflict of interest:**The authors declare that there are no conflicts of interest.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "1. ", "Field of the Invention\nThe present invention relates to satellite dish antenna mounts, and more particularly to a conveniently transported mount assembly useful to combine into a dish antenna mount that may be generally fixed at various selected orientations.", "\n2. ", "Description of the Prior Art\nThe transmission of television and other similar signals has gone through several evolutions, first in the form of broadband radio signal then followed by various land lines or cable networks. ", "In each instance either the physical burden of various in-ground or overhead cables or the width of the useable electromagnetic spectrum have limited the number of available programming sources. ", "The granulation of available programming bandwidths, however, has recently gone through a dramatic evolutionary step with the recent advent of transmission techniques relying on geosynchronous satellites each serving as the signal emitting source for a particular program grouping, this evolution then being further reinforced by legislation like the Telecommunications Act of 1996.", "\nIn this latter method the satellites associated with each particular signal group are distributed equatorially above the Earth, with a singular line of sight set of coordinates then ascribed to each geographic location. ", "These alignment coordinates are then used for orienting the sensing axes of highly polarized antennae generally known as a satellite dish. ", "The fixed nature of the viewing coordinates has led to a generally universal, more or less permanent, installation process with the fixed satellite dish mounting structure positioned adjacent the residence that is serviced thereby and the installation process then providing the customer garnering mechanism for a particular program source.", "\nIn typical practice the coordinates for each antenna location are expressed as a corrected magnetic North azimuth and degrees of elevation from the local horizontal plane. ", "As a consequence installation facility has become generally widespread and along with the wide acceptance of satellite programming by fixed residences there has also now emerged a robust trend to implement movable structures like recreational vehicles or motor homes with deployable antenna mounts. ", "These deployable mounts most often follow the earlier practices of satellite based surveying or measuring antennae typically supported on an adjustable tripod, such as those described in U.S. Pat. ", "No. ", "4,767,090 issued to Hartman, et al.; ", "U.S. Pat. ", "No. ", "5,249,766 issued to Vogt; U.S. Pat. ", "No. ", "5,614,918 issued to Dinardo, et al.; ", "U.S. Pat. ", "No. ", "5,769,370 issued to Ashjace; U.S. Pat. ", "No. ", "6,450,464 issued to Thomas; and others. ", "Similar tripod mounted structures are also commercially sold, as for example the tripod mount sold under the model designation TR-2000 Tripod/Base Mount by the Winegard Company, 3000 Kirkwood Street, Burlington, Iowa 52601-2000. ", "While suitable for the purposes intended each of the foregoing entail complex assortments of parts which include metal structures that distort or wholly obliterate any magnetic compass reading, while those made wholly of plastic like the antenna mount sold under the mark or model xe2x80x9cThe Buoyxe2x80x9d by Camping World, Three Springs Road, P.O. Box 90017, Bowling Green, Ky. 42102-9017, lack the leveling indicia for alignment precision. ", "Thus either the resulting measurement and erection complexity or lack of precision have unnecessarily detracted from the use convenience and proliferation of the deployable mount has been less than ringing in the recent past. ", "A conveniently assembled, non-metallic mount structure is therefore extensively desired and it is one such structure that is disclosed herein.", "\nAccordingly, it is the general purpose and object of the present invention to provide an erectable antenna mount assembly all the parts thereof being formed from non-magnetic materials.", "\nOther objects of the present invention are to provide a conveniently erected antenna mount assembly supported on a base container that is selectively ballasted by storing water therein.", "\nFurther objects of the invention are to provide an array of cooperating parts that are conveniently interlocked and thereafter aligned to support an antenna dish.", "\nYet additional objects of the invention are to provide an interlocking array of parts that is easily assembled to form a satellite dish antenna mount provided with structural interlocks that are engaged without substantial ambiguity.", "\nBriefly, these and other objects are accomplished within the present invention by providing a generally hollow base formed as an annular liquid container having the central opening therein keyed and dimensioned for conforming orthogonal receipt of a similarly keyed end of a cylindrical mount. ", "The other end of the mount is then provided with a selectively releasable universal swivel fixed by threaded advancement of the bottom end of a support post extending therefrom. ", "The support post, in turn, terminates at the other end in a dished cavity into which a leveling bubble assembly is placed which is then useful to align the support post on the cylindrical mount to a generally vertical alignment regardless of the inclination of the hollow base. ", "Once aligned the base is then filled with water to provide ballast fixing the base on the ground.", "\nPreferably the hollow base, the cylindrical mount and the support post are all formed of a polymeric material structure, such as polyvinyl chloride or other generally rigid polymer structure having material properties that allow the machining and cutting thereof. ", "Similarly, the pivoting mechanism fixing the support post alignment relative the cylindrical mount also comprises non-magnetic components, the non-ferrous assembly therefore allowing use of an inexpensive magnetic compass to assist in the orientation of the base along a predetermined azimuth. ", "In this manner the induced magnetic distortion errors that are usually associated with unwanted distortions of the local magnetic field are wholly avoided. ", "This cooperative structural arrangement is further simplified by way of a threaded extension of the mounting post into a domed ball surface captured between a cap on the end of the cylindrical mount by a helical spring and a dished surface within the cylinder opposing the threaded extension or the post so that a partial turn thereof then provides the frictional interlock to fix its generally vertical alignment as determined by the bubble level seated in the free end of the post. ", "A satellite dish antenna, conventionally provided with elevation adjustment, can then be fixed to the mounting post along the azimuth referenced to the compass.", "\nOne will appreciate that the planform of the base container and its several surfaces may be variously shaped for clear visual indication of the azimuth alignment thereof. ", "Moreover various storage provisions may be formed in the surfaces of the container that retain the compass and the component array of the cylindrical support assembly. ", "In this manner a convenient, easily transported and easily aligned antenna mount assembly is provided that is useful at all geographic locations." ]

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[ "1. ", "Field of the Invention\nThe present invention relates to an installation apparatus of a sterilization verifying device and an installation method.", "\n2. ", "Description of the Related Art\nIt is preferable that a sterilizing effect is verified in an object for sterilization to verify the sterilizing effect inside the object, but conventionally it is practically impossible to mount an indicator capable of verifying a sterilizing effect into an object for sterilization. ", "Thus, a device for creating a virtual environment which is similar to an interior environment of the object for sterilization to verify a sterilizing effect is used.", "\nJapanese Patent Application Laid-Open No. ", "2005-176939 discusses a technology for mounting an indicator to a device for verifying a sterilizing effect. ", "Specifically the technology is for mounting an indicator into an indicator case from a cap of an end of the indicator case. ", "In Japanese Patent Application Laid-Open No. ", "2005-176939, the device for verifying a sterilizing effect is a precision instrument, and thus in order to replace an indicator, a part for mounting the indicator of the device needs to be opened to mount the indicator and finally the part for mounting the indicator of the device needs to be closed, which is very inconvenient. ", "In particular, operators or nurses in charge of sterilizing operations in the medical field are mostly women, and thus the opening/closing operation of such a device is not suitable for weak women." ]

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[ "Q:\n\nCopy files with renaming\n\nI have a huge file tree. ", "Some files have same name but in different case, e.g., some_code.c and Some_Code.c.", "\nSo when I'm trying to copy it to an NTFS/FAT filesystem, it asks me about whether I want it to replace the file or skip it.", "\nIs there any way to automatically rename such files, for example, by adding  (1) to the name of conflict file (as Windows 7 does)?", "\n\nA:\n\nMany GNU tools such as cp, mv and tar support creating backup files when the target exists. ", "That is, when copying foo to bar, if there is already a file called bar, the existing bar will be renamed, and after the copy bar will contain the contents of foo. ", "By default, bar is renamed to bar~, but the behavior can be modified:\n # If a file foo exists in the target, then…\ncp -r --backup source target # rename foo → foo~\ncp -r --backup=t source target # rename foo → foo.~1~ (or foo.~2~, etc)\n\nThere are other variants, such as creating numbered backups only when one already exists. ", "See the coreutils manual for more details.", "\n\nA:\n\nI tried \napropos copy | grep \"(1)\" \n\nto find possible candidates, and mcopy showed up. ", "\nman mcopy \n\nshows a promising option -D clash-option isn't that cool? ", "But not so cool - it isn't described. ", "But there are some hints to mtools.dvi, which I searched on my system, without success, and via google, without success, but then, with google, I searched directly for mcopy clash-option and found this site. ", "\nI made a short test\nmcopy -D A f* a \n\nto tests for autorename and targetdir a - instead of autorenaming it asked me for every file to ignore or override, that stupid s... . ", "\nMy version is mtools-4.0.10 and the help page is from 1996 - 15 years old. ", "Should we really lost some features, meanwhile? ", "\nI would split the work into two steps: \n\nMake a short function, which generates a unique name for a file, if that name is occupied. ", "\nRun find, and execute that script for every file you wish to copy. ", "\n\nShall we assist in this approach? :)", "\nHere is a script, to autorename files: \n#!", "/bin/bash\n\nname=$1\ntarget=$2\n\nautorename () {\nname=$1\ntarget=$2\nno=$3 \n\ntest -e ${target}/${name}.$no && autorename ${name} ${target} $((no+1)) || cp ${name} ${target}/${name}.$no \n\n}\n\ntest -e ${target}/${name} && autorename ${name} ${target} 0 || cp ${name} ${target} \n\nand this is my test invocation:\nfind -maxdepth 1 -name \"fo*\" -type f -exec ./autorename.sh {} /mnt/hidden/test/a \";\"\n\nNote: -maxdepth, -name and -type where used to restrict the number of affected files dramatically. ", "\nI didn't test the script for deeper file structures, nor for blanks in filenames and other, funky characters like linefeed, pagefeed and so on. ", "\nI used .1 because it doesn't make trouble in most commands, while a ( and a ) often need masking. ", "\n\n" ]

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[ "Health experts have developed a package of food taxes and subsidies that would save Australia $3.4bn in healthcare costs without affecting household food budgets.", "\n\nLinda Cobiac, a senior research fellow at the University of Melbourne’s school of public health, led the research published on Wednesday in the journal Plos Medicine.", "\n\nCobiac and her team used international data from countries that already have food and beverage taxes such as Denmark, but tweaked the rate of taxation and also included a subsidy for fresh fruit and vegetables so the total change to the household budget would be negligible.", "\n\nThey then modelled the potential impact on the Australian population of introducing taxes on saturated fat, salt, sugar and sugar-sweetened beverages, and a subsidy on fruits and vegetables. ", "Their simulations found the combination of the taxes and subsidy could result in 1.2 additional years of healthy life per 100 people alive in 2010, at a net cost-saving of $3.4bn to the health sector.", "\n\n“Few other public health interventions could deliver such health gains on average across the whole population,” Cobiac said.", "\n\nThe sugar tax produced the biggest gains in health, followed by the salt tax, the saturated fat tax and the sugar-sweetened beverage tax.", "\n\nThe fruit and vegetable subsidy, while cost-effective when added to the package of taxes, did not lead to a net health benefit on its own, the researchers found.", "\n\nA co-author of the paper, Prof Tony Blakely, said this was because although a fruit and vegetable subsidy alone would encourage people to eat more fresh foods, previous studies of consumer behaviour had found they would spend the money saved on sugary foods.", "\n\nThe researchers suggest introducing a tax of $1.37 for every 100 grams of saturated fat in those foods with a saturated fat content of more than 2.3%, excluding milk; a salt tax of 30 cents for one gram of sodium above Australian maximum recommended levels; a sugar-sweetened beverage tax of 47 cents a litre; a fruit and vegetable subsidy of 14 cents for every 100 grams; and a sugar tax of 94 cents for every 100ml in ice-cream with more than 10 grams of sugar per 100 grams; and 85 cents for every 100 grams in all other products.", "\n\nThe taxes exclude fresh fruits, vegetables, meats and many dairy products.", "\n\n“You need to include both carrots and sticks to change consumer behaviour and to encourage new taxes,” Blakely said. “", "That’s where this paper is cutting edge internationally.", "\n\n“We have worked out the whole package of taxes with minimal impact on the budget of the household, so you can see an overall gain for the government. ", "The government would be less interested in the package if it was purely punitive, but this provides subsidies and savings to health spending that could be reinvested back into communities and services.”", "\n\nHe said taxing junk foods also prompted food manufacturers to change their products and make them healthier to avoid the taxes.", "\n\n“For those who might say this is an example of nanny state measures, let’s consider that we don’t mind asbestos being taken out of buildings to prevent respiratory disease, and we’re happy for lead to be taken from petrol. ", "We need to change the food system if we are going to tackle obesity and prevent disease.”", "\n\nA health economist at the Grattan Institute, Stephen Duckett, said the researchers had put together a careful and strong study and set of tax and subsidy suggestions. “", "This is a very good paper,” he said.", "\n\n“In my view, we should be starting to tax sugary drinks as a first step. ", "Nearly every week there’s a new study citing the benefits of a sugary drinks tax and and nearly every month another country adopts it as a policy. ", "It’s quickly being seen as an appropriate thing to do to address the obesity epidemic.”", "\n\nA Grattan Institute report published in November found introducing an excise tax of 40 cents for every 100 grams of sugar in beverages as part of the fight against obesity would trigger a 15% drop in the consumption of sugary drinks. ", "Australians and New Zealanders consume an average of 76 litres of sugary drinks per person every year.", "\n\nIn a piece for the Medical Journal of Australia published on Monday, the chair of the Council of Presidents of Medical Colleges, Prof Nicholas Talley, wrote that “the current lack of a coordinated national approach is not acceptable”.", "\n\nMore than one in four Australian children are now overweight or obese, as are more than two-thirds of all adults.", "\n\nTalley proposed a six-point action plan, which included recognising obesity as a chronic disease with multiple causes. ", "He also called for stronger legislation to reduce unhealthy food marketing to children and to reduce the consumption of high-sugar beverages, saying a sugar-sweetened beverage tax should be introduced.", "\n\n“There is evidence that the food industry has been a major contributor to obesity globally,” he wrote. “", "The health of future generations should not be abandoned for short-term and short-sighted commercial interests.”" ]

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[ "We've seen our share of construction near the radio station at 82nd Street and Quaker Avenue, so of course the guys at Pure Water Ice & Tea Company (3333 82nd Street) had to find something humorous to say.", "\n\nWhen dealing with ongoing construction like this, residents are constantly re-routing themselves to avoid the latest lane closures. ", "But as frustrating as traffic backups may be, a sense of humor definitely goes a long way toward making the best of it.", "\n\nIt's not the first time the business has gotten into the funny sign game, either. ", "During Texas Tech's 2018 football season, they put up signs trolling both UT and Oklahoma.", "\n\nThank you, Pure Water, for adding some humor to our otherwise strenuous trek through lane closures and construction. ", "And thank you to Lubbock resident Annette Castellano for sharing the hilarious picture with us." ]

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[ "December 3-6, 2012\n\nEnthusiasm for bereavement support group counseling has burgeoned in recent years. ", "And, while training opportunities that advance our understanding of the bereavement process have become more available recently, less work has been done on the support group models of care. ", "This seminar helps fill this gap; topics covered will include:\n\nSupport group leadership skills\n\nBarriers to effectiveness in support group counseling\n\nDetailed guidelines for operational practices (such as size of group, length and frequency of sessions)" ]

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[ "BBC tries to stoke racial tensions in Scotland\n\nMy letter of complaint:\n\nDear Sir / Madam,\n\nOn Tuesday 10th of March the BBC website reported on an opinion poll commissioned by the BBC into attitudes to immigration in Scotland. ", "The article, entitled “BBC poll suggests 64% of Scots want immigration reduced”, can be found here: http://www.bbc.co.uk/news/uk-scotland-31800374\n\nThe BBC guidelines on opinion polls clearly state “We should not headline the results of an opinion poll unless it has prompted a story which itself deserves a headline and reference to the poll’s findings is necessary to make sense of it”.", "\n\nThe guideline exists for an excellent reason, which is that it is not the BBC’s role to determine the political questions of the day, but rather to report on them.", "\n\nThis is especially egregious behaviour in a tense pre-election context. ", "I find it hard to imagine what the BBC hoped to achieve by commissioning this poll in the first place.", "\n\nYours\n\nAlistair Davidson\n\n[UPDATE: Scotland 2015, the BBC’s flagship current affairs show, is following up on this story by inviting UKIP on to debate the main Scottish parties, except the Greens.]", "\n\n[UPDATE 2: And “the debate will continue” on Morning Call tomorrow. ", "Joy!]" ]

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[ "The present invention relates to a novel amine having the name 2-(3-(aminomethyl)-3,5,5-trimethylcyclohexyl)propane-1,3-diamine (AM-CPDA), referred to hereinbelow as AM-CPDA, to a process for its production and to its use.", "\n2-(3-(aminomethyl)-3,5,5-trimethylcyclohexyl)propane-1,3-diamine (AM-CPDA), referred to hereinbelow as AM-CPDA, has the chemical structure depicted in structural formula 1.", "\n\nIt is known that amines may be employed as hardeners in epoxy systems. ", "Epoxy resins are prepolymers comprising two or more epoxy groups per molecule. ", "The reaction of these resins with a range of hardeners affords crosslinked polymers. ", "An overview of possible resins and hardeners, their use and properties is given in H. Schumann, “Handbuch Betonschutz durch Beschichtung”, Expert Verlag 1992, pages 396-428." ]

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[ "Theresa May will launch a fresh bid to win support for her rejected Brexit deal by trying to bypass the European Union and secure a bilateral Brexit treaty with Ireland, according to reports.", "\n\nThe move, which comes as No 10 expresses extreme concern at a backbench bid to give parliament control of Brexit, would see the UK try to convince Ireland to agree a plan for keeping the Northern Ireland border open after Britain leaves the EU.", "\n\nOfficials are said to believe that such an agreement could remove the need for the controversial backstop part of Ms May’s Brexit deal, which is the leading cause of Tory and DUP opposition to the plan and the main reason it was overwhelmingly rejected by MPs last week.", "\n\nMs May will update the Commons on Monday on how she plans to proceed after the crushing defeat.", "\n\nUnder the new proposal being discussed by No 10, the Sunday Times reports, the UK would try to convince the Irish government to negotiate a treaty that would remove the need for the backstop, which Brussels insisted on as an insurance policy to ensure an open border is maintained even if the EU and UK cannot agree a trade deal.", "\n\nThe arrangement would see the UK enter into a temporary customs union with the EU, and Northern Ireland agree to abide by European rules on goods until a subsequent deal was reached.", "\n\nA Downing Street source said talk of a bilateral agreement with Ireland was \"not something we recognise\".", "\n\nLiam Fox, the international trade secretary, appeared to confirm the plan, however, telling the BBC’s Andrew Marr Show: “We have to compromise on the backstop. ", "If we’re to get the agreement through, we absolutely have to do that. ", "The question is how we find a way to do that.”", "\n\nAsked what such a compromise might involve, he said: “It’s getting an agreement with Ireland on an alternative mechanism to ensure that we don’t get friction across the Norther Ireland-Ireland border.”", "\n\nMr Fox said both the UK and Irish government shared a desire to preserve an open border in Northern Ireland, adding: “The question is can we achieve what the Irish government wants and what we want by a different mechanism.”", "\n\nThe government will “explore ways” to “find an alternative mechanism to ensure that we give the Irish government what they want, which is that we end up with no hard border”, he added.", "\n\nBrexit deal vote: Opposing groups of protesters gather by parliament Show all 20 1 /20 Brexit deal vote: Opposing groups of protesters gather by parliament Brexit deal vote: Opposing groups of protesters gather by parliament Brexit supporters outside parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester adjusts her pro-EU wig AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament A message to Jeremy Corbyn in support of a people’s vote Getty Brexit deal vote: Opposing groups of protesters gather by parliament A mock Titanic captained by Theresa May heads towards an iceberg in a stunt by campaigning group Avaaz AP Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters outside parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides are in close contact outside of parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament Paintings of Theresa May and Jeremy Corbyn Getty Brexit deal vote: Opposing groups of protesters gather by parliament Former Ukip leader Nigel Farage speaks to the media at the protests outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament A pro-Brexit protester in Parliament Square Getty Brexit deal vote: Opposing groups of protesters gather by parliament Opposing protesters share the space outside parliament Getty Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester holds EU balloons outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters stand on Westminster Bridge PA Brexit deal vote: Opposing groups of protesters gather by parliament Former Ukip leader Nigel Farage speaks to the media at the protests outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters demonstrate outside the Houses of Parliament EPA Brexit deal vote: Opposing groups of protesters gather by parliament A pro-Brexit protester sets up outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament An Avaaz campaigner holds a People’s Vote life float Reuters Brexit deal vote: Opposing groups of protesters gather by parliament A demonstrator holds a sign advocating a no-deal Brexit outside parliament AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester waves an EU flag on Westminster Bridge PA Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides demonstrate outside parliament AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides stand near parliament Reuters\n\nDublin moved swiftly to pour cold water on the suggestion.", "\n\nSimon Coveney, the Irish foreign minister, wrote on Twitter: “As Brexit dominates news coverage, no surprise that some analysis today gets it wrong. ", "I can reassure you the Irish government’s commitment to the entire [withdrawal agreement] is absolute – including the backstop to ensure, no matter what, an open border between Ireland + NI and the [Good Friday Agreement] are protected.”", "\n\nAnd an Irish government source told the Sunday Times that a bilateral treaty “doesn’t sound like something we would entertain”.", "\n\nMs May’s chief of staff, Gavin Barwell, has reportedly told cabinet ministers that, if the plan fails, the prime minister could seek to secure more support for her deal by announcing she will step down in May.\n\nMs May briefed her cabinet on her next steps during a conference call on Sunday afternoon.", "\n\nThe latest twist comes as a cross-party group of backbenchers prepares to try to amend whatever plan Ms May puts forward in order to give parliament the right to seize control of Brexit.", "\n\nThe proposal, led by former attorney general Dominic Grieve, would remove the government’s power to choose what parliament debates and instead prioritise any motion backed by 300 MPs from at least five parties – significantly less than a Commons majority.", "\n\nJeremy Corbyn says Theresa May's Brexit plan is 'quite clearly a dead deal'\n\nA separate plan being worked on by senior parliamentarians, including Labour’s Yvette Cooper and former Tory ministers Nick Boles and Nicky Morgan, would force the government to delay Brexit if a deal is not approved within weeks.", "\n\nA Downing Street spokesperson said: “The British public voted to leave the European Union and it is vital that elected politicians deliver upon that verdict.", "\n\n“Any attempt to remove the government’s power to meet the legal conditions of an orderly exit at this moment of historic significance is extremely concerning.”", "\n\nIn a sign of growing concern among Eurosceptics that the amendments could lead to Brexit being delayed or reversed, leading Tory Brexiteer Jacob Rees-Mogg, a vocal critic of Ms May’s deal, said it would be better to leave the EU on the terms of the prime minister’s plan than not leave at all.", "\n\nWriting in the Mail on Sunday, he called on the Conservatives to “come together in the national interest”. ", "He added: “If I had to choose between no deal and Mrs May’s original accord, I would have no hesitation of opting for no-deal Brexit, but even Mrs May’s deal would be better than not leaving at all." ]

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[ "Hundreds of schoolchildren have been drafted in to make Amazon's Echo Dot and Kindle devices illegally in China, a report has revealed.", "\n\nInvestigators at Amazon supplier Foxconn's factory found children were working gruelling night-shifts in order to meet demands in the city of Hengyang in Hunan Province.", "\n\nTeenagers are encouraged by local schools and colleges to become 'interns' at the factory, where their teachers are paid to accompany them to work.", "\n\nMore than 1,000 youngsters stand for hours on end throughout the night doing repetitive work which requires little technical training, China Labor Watch found.", "\n\nHuang Xuehua, 24, from Guangdong province works inside a Foxconn factory in the township of Longhua in the southern Guangdong province\n\nThe dorm room interior where workers live at the Foxconn factory in Hengyang in Hunan Province\n\nOne 17-year-old was required to apply a layer of plastic film to around 3,000 Echo Dots every day\n\nThe Foxconn plant in Hunon province also makes Amazon Kindle e-book reading devices (pictured, office buildings in Silicon Valley)\n\nOne 17-year-old told The Guardian she was required to apply a layer of plastic film to around 3,000 Echo Dots every day.", "\n\nShe was initially told she would work eight-hour shifts, five days a week, but that soon jumped to ten-hours a day in a six day week.", "\n\n'I tried telling the manager of my line that I didn’t want to work overtime.' ", "She told The Guardian, 'But the manager notified my teacher and the teacher said if I didn’t work overtime, I could not intern at Foxconn and that would affect my graduation and scholarship applications at the school.", "\n\n'I had no choice, I could only endure this'\n\nChinese law allows children aged 16 and over to work in factories, but they are not supposed to work overtime or during the night.", "\n\nMany of the workers are packed in factory dorm rooms which were found to be lacking fire exits, extinguishers and had squalid bathrooms.", "\n\nChina Labor Watch investigators could find no presence of a labour union and staff were subjected to verbal abuse by line managers.", "\n\nMore than 40 percent of the workforce at the Foxconn plant are dispatch workers - poorly trained and denied sick leave - in violation of China's 10 percent law on dispatch workers.", "\n\nThe exterior of the Foxconn plant in the city of Hengyang in Hunan Province\n\nChinese law mandates dispatch workers must receive at least 24 hours of training, China Labor Watch found those in Hengyang received just eight.", "\n\nWorkers at the factory were also required to put in 100 hours of overtime per month in 'peak season,' despite it being illegal to work anymore than 36 hours of overtime.", "\n\nDuring the off season workers made an average of just £290 a month, while the average workers in Hengyang take home £600.", "\n\nFoxconn, a Taiwanese multinational, which also makes iPhones for Apple admitted to the Guardian it had employed students illegally and would take remedial action.", "\n\nIn a statement provided to the paper it said: 'We have doubled the oversight and monitoring of the internship program with each relevant partner school to ensure that, under no circumstances, will interns [be] allowed to work overtime or nights.", "\n\n'There have been instances in the past where lax oversight on the part of the local management team has allowed this to happen and, while the impacted interns were paid the additional wages associated with these shifts, this is not acceptable and we have taken immediate steps to ensure it will not be repeated.'", "\n\nWorkers eat their lunch at a restaurant inside a Foxconn factory in the township of Longhua in Shenzhen\n\nHowever, Foxconn defended its use of children and said it provided an 'opportunity to gain practical work experience and on-the-job training.'", "\n\nAmazon, whose chairman Jeff Bezos is the richest man in the world, said it would address the allegations with Foxconn at the highest level.", "\n\nAmazon's statement to China Labor Watch said: 'Amazon recognizes our responsibility to ensure the well-being of factory workers manufacturing products for Amazon ...\n\n'Where appropriate, Amazon uses independent auditors to verify compliance with expectations in our Supplier Code of Conduct.'" ]

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[ ". ", "Opoziția e altundeva, nu e în partid\", a declarat Mang.", "\n\n\n\nGabriela Firea a transmis vineri că nu se află în fruntea niciunei răzmerițe, dar că se va alătura oricărei inițiative pentru „modernizarea” PSD și că Liviu Dragnea a oferit primele 3 locuri de pe lista pentru europarlamentare „la cel puțin 30 de colegi”. „", "Dovada cea mai bună a faptului că am dreptate este modul în care Liviu Dragnea a înțeles să răspundă la acuzațiile pe care i le-am adus. ", "În loc să creeze cadrul unei dezbateri deschise și principiale în partid, a găsit de cuviință să-i convoace la sediul central pe liderii de organizații, unul câte unul, sau în grupuri mici, după afinități și, sub pretextul unor discuții referitoare la organizarea referendumului, să încerce să-i intimideze sau, după caz, să-i fidelizeze, cu amenințări mai mult sau mai puțin voalate, sau cu promisiuni mai mult sau mai puțin iluzorii. ", "Doar din informațiile pe care le am eu, a oferit primele 3 locuri pe lista de la europarlamentare la cel puțin 30 de colegi!\", ", "a spus aceasta.", "\n\n\n\nEa a conchis că PSD s-a prăbușit în sondaje. „", "Mulți dintre colegii sau votanții noștri văd în Liviu Dragnea simbolul luptei împotriva statului paralel și a președintelui Iohannis. ", "Este o percepție pur subiectivă, pentru că faptele arată cu totul altceva. ", "După alegerile din 2016, în ciuda multor măsuri bune, cu mare impact în rândul populației, PSD s-a prăbușit în sondaje ca intenție de vot, în timp ce toți adversarii noștri capitalizează această scădere, valul de ură împotriva PSD nu a fost niciodată atât de puternic, iar noi înfruntăm această realitate sub conducerea unui președinte vulnerabil din multe puncte de vedere, cu o cotă de încredere cu mult sub cea a partidului. ", "În condițiile acestea, e limpede pentru oricine că bătăliile politice care ne așteaptă în 2019 sunt pierdute din start! ", "În mai puțin de 4 luni, Bucureștiul va deveni capitala Europei pentru jumătate de an, odată cu preluarea de către România a președinției rotative a Consiliului Uniunii Europene. ", "Cred că avem acum o ultimă șansă de a ne prezenta în fața opiniei publice din întreaga Uniune ca partid modern, democratic, pro-european, capabil să susțină cu legitimitate interesele românilor\", a afirmat acesta.", "\n\n\n\n\n\n\n\n„Am avut în această după amiază o întâlnire cu colegii din PSD din Transilvania. ", "Am discutat câteva ore, fiecare cu argumentele sale, despre direcția în care trebuie să se îndrepte pe termen scurt și mediu Partidul Social Democrat. ", "M-am bucurat enorm să văd că părerile coincid în cele mai multe privințe și am stabilit că începând de astăzi vom vorbi între noi, membrii PSD din Transilvania, mult mai des și vom avea poziții unitare atunci când se va vorbi despre viitorul nostru\", a scris sâmbătă, pe Facebook, Gabriel Zetea, vicepreședinte PSD și președinte PSD Maramureș.", "Potrivit acestuia, organizațiile județene PSD din Ardeal susțin „fără rezerve” Guvernul. „", "Susținem fără rezerve Guvernul PSD-ALDE și aplicarea în continuare a Programului de Guvernare. ", "Toate atacurile și disensiunile publice între membrii PSD cu funcții de conducere de la București trebuie să înceteze rapid pentru a ne concentra pe rezultatele guvernării și pentru a ne putea ține de cuvântul dat românilor în 2016. ", "Cerem președintelui Liviu Dragnea convocarea în cel mai scurt timp posibil a unei ședințe (sau a câte ședințe este nevoie) a Comitetului Executiv Național pentru a clarifica eventualele nemulțumiri a unor colegi. ", "PSD este un partid democratic unde fiecare are dreptul să își exprime liber punctul de vedere dar ne dorim să auzim nemulțumirile în cadrul ședințelor statutare ale partidului și nu în mass media\", a precizat Zetea.", "Zetea spunea vineri că „nimeni nu va achiesa” în partid la ideea schimbării din funcție a liderului formațiunii, Liviu Dragnea, atâta vreme cât nu există o „alternativă conturată” și că, personal, el nu vede „astăzi” această alternativă în PSD.De asemenea, președintele PSD Bihor, Ioan Mang, declara vineri că este nevoie de organizarea ”rapidă” a unei ședințe CExN , săptămâna viitoare, pentru a se stabili prin vot dacă partidul „este pe ideea dnei Firea sau nu”.", "„Părerea mea personală este că, întrucât dna Firea a ieșit astăzi cu alte știri și cu alte...trebuie organizat un CEx și stabilit dacă partidul este pe ideea dnei Firea sau nu. ", "Dânsa, până la urmă, și oricine din partidul ăsta trebuie să înțeleagă că dacă ai o propunere o discuți în partid, se supune la vot, dacă propunerea ta are voturile necesare, în regulă. ", "Dacă nu, subiectul este rămâi în partid și respecți decizia majorității sau pleci, că nu putem să stăm așa la infinit, decidem una și a doua zi ieșim pe presă și spunem altceva\", a declarat Ioan Mang.", "Întrebat dacă vrea ca Gabriela Firea să fie propusă spre sancționare în PSD dacă va continua cu declarațiile publice critice, Mang a răspuns afirmativ. „", "Nu numai dna Firea, oricine. ", "Dacă discuția are loc în partid și majoritatea decide că nu se urmează acea cale, discuția trebuie să înceteze pentru un membru care vrea să rămână în partid, într-o situație în care cel mai important lucru este să ne realizăm programul de guvernare. ", "Dacă vom discuta doar despre noi, în loc să muncim, să ne facem treaba, nu am făcut nimic\", a precizat liderul PSD Bihor.", "Mang a mai declarat că a participat joi, la sediul central PSD, la o discuție între „mai mulți colegi\", în prezența președintelui PSD Liviu Dragnea, privind convocarea unei ședințe CExN. „Ideea a fost dacă e nevoie de Comitet Executiv rapid, adică în următoarele două săptămâni. ", "Nu a fost o decizie, a fost o discuție între colegi, am fost mai mulți colegi\", a spus el. ", "Liderul județean PSD a apreciat că, din punctul său de vedere, o ședință CExN organizată săptămâna viitoare ar putea să „închidă\" subiectul presupusei scrisori a nemulțumiților din partid.", "„Poate dacă îl facem mai repede, săptămâna viitoare, se încheie odată subiectul de presă, că nu există nicio scrisoare, nu a semnat nimeni, cu câți am discutat, inclusiv cu dl Stănescu, nu există o astfel de scrisoare, adică până la urmă trebuie să închidem subiectul ăsta. ", "Altfel, lumea începe să dea telefoane, mă sună" ]

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[ "\nShow HN: Instantly Find anything across your email, cloud drives, and more - ranmancan\nhttps://www.justgoferit.com/get-gofer\n======\nranmancan\nHey All,\n\nI'm part of the team at Gofer - a free productivity tool to easily find and\nmanage information from across your different apps and services.", "\n\nWe're looking for productivity enthusiasts who would like to receive early\naccess and try it out :)\n\nGofer features many cool things, such as smart auto-tagging, allowing to\nintuitively slice and dice your way to a file or mail in seconds. ", "It's also\nSAFE, because it runs on the desktop, so no personal information ever leaves\nyour computer. ", "Only the local instance receives permission to read your data.", "\n\nIts free for anyone to use (we'll be adding paid premium features in the\nfuture).", "\n\nHappy to hear your thoughts!", "\n\n" ]

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[ "/*\n * Copyright 2017-2020 original authors\n *\n * Licensed under the Apache License, Version 2.0 (the \"License\");\n * you may not use this file except in compliance with the License.", "\n * You may obtain a copy of the License at\n *\n * https://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing, software\n * distributed under the License is distributed on an \"AS IS\" BASIS,\n * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n * See the License for the specific language governing permissions and\n * limitations under the License.", "\n */\npackage io.micronaut.core.util;\n\nimport edu.umd.cs.findbugs.annotations.", "Nullable;\nimport java.lang.reflect.", "Array;\nimport java.util.*;", "\n\n/**\n * Utility methods for working with arrays.", "\n *\n * @author Graeme Rocher\n * @since 1.0\n */\npublic class ArrayUtils {\n\n /**\n * An empty object array.", "\n */\n public static final Object[] EMPTY_OBJECT_ARRAY = new Object[0];\n\n /**\n * Concatenate two arrays.", "\n *\n * @param a The first array\n * @param b The second array\n * @param <T> The array type\n * @return The concatenated array\n */\n public static <T> T[] concat(T[] a, T... b) {\n int bLen = b.length;\n\n if (bLen == 0) {\n return a;\n }\n int aLen = a.length;\n if (aLen == 0) {\n return b;\n }\n\n @SuppressWarnings(\"unchecked\")\n T[] c = (T[]) Array.newInstance(a.getClass().getComponentType(), aLen + bLen);\n System.arraycopy(a, 0, c, 0, aLen);\n System.arraycopy(b, 0, c, aLen, bLen);\n\n return c;\n }\n\n /**\n * Concatenate two byte arrays.", "\n *\n * @param a The first array\n * @param b The second array\n * @return The concatenated array\n */\n public static byte[] concat(byte[] a, byte... b) {\n int bLen = b.length;\n\n if (bLen == 0) {\n return a;\n }\n int aLen = a.length;\n if (aLen == 0) {\n return b;\n }\n\n byte[] c = new byte[aLen + bLen];\n System.arraycopy(a, 0, c, 0, aLen);\n System.arraycopy(b, 0, c, aLen, bLen);\n\n return c;\n }\n\n /**\n * Whether the given array is empty.", "\n *\n * @param array The array\n * @return True if it is\n */\n public static boolean isEmpty(Object[] array) {\n return array == null || array.length == 0;\n }\n\n /**\n * Whether the given array is not empty.", "\n *\n * @param array The array\n * @return True if it is\n */\n public static boolean isNotEmpty(Object[] array) {\n return !", "isEmpty(array);\n }\n\n /**\n * Produce a string representation of the given array.", "\n *\n * @param array The array\n * @return The string representation\n */\n public static String toString(@Nullable Object[] array) {\n String delimiter = \",\";\n return toString(delimiter, array);\n }\n\n /**\n * Produce a string representation of the given array.", "\n *\n * @param delimiter The delimiter\n * @param array The array\n * @return The string representation\n */\n public static String toString(String delimiter, @Nullable Object[] array) {\n if (isEmpty(array)) {\n return \"\";\n }\n List<Object> list = Arrays.asList(array);\n return CollectionUtils.toString(delimiter, list);\n }\n\n /**\n * Produce an iterator for the given array.", "\n * @param array The array\n * @param <T> The array type\n * @return The iterator\n */\n public static <T> Iterator<T> iterator(T...array) {\n if (isNotEmpty(array)) {\n return new ArrayIterator<>(array);\n } else {\n return Collections.emptyIterator();\n }\n }\n\n /**\n * Produce an iterator for the given array.", "\n * @param array The array\n * @param <T> The array type\n * @return The iterator\n */\n public static <T> Iterator<T> reverseIterator(T...array) {\n if (isNotEmpty(array)) {\n return new ReverseArrayIterator<>(array);\n } else {\n return Collections.emptyIterator();\n }\n }\n\n /**\n * Iterator implementation used to efficiently expose contents of an\n * Array as read-only iterator.", "\n *\n * @param <T> the type\n */\n private static final class ArrayIterator<T> implements Iterator<T>, Iterable<T> {\n\n private final T[] _a;\n private int _index;\n\n private ArrayIterator(T[] a) {\n _a = a;\n _index = 0;\n }\n\n @Override\n public boolean hasNext() {\n return _index < _a.length;\n }\n\n @Override\n public T next() {\n if (_index >= _a.length) {\n throw new NoSuchElementException();\n }\n return _a[_index++];\n }\n\n @Override public void remove() {\n throw new UnsupportedOperationException();\n }\n\n @Override public Iterator<T> iterator() {\n return this;\n }\n }\n\n /**\n * Iterator implementation used to efficiently expose contents of an\n * Array as read-only iterator.", "\n *\n * @param <T> the type\n */\n private static final class ReverseArrayIterator<T> implements Iterator<T>, Iterable<T> {\n\n private final T[] _a;\n private int _index;\n\n private ReverseArrayIterator(T[] a) {\n _a = a;\n _index = a.length > 0 ? ", "a.length : -1;\n }\n\n @Override\n public boolean hasNext() {\n return _index > -1;\n }\n\n @Override\n public T next() {\n if (_index >= -1) {\n throw new NoSuchElementException();\n }\n return _a[_index--];\n }\n\n @Override public void remove() {\n throw new UnsupportedOperationException();\n }\n\n @Override public Iterator<T> iterator() {\n return this;\n }\n }\n}\n" ]

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[ "Donald West VanArtsdalen\n\nDonald West VanArtsdalen (sometimes listed as Van Artsdalen; October 21, 1919 – May 21, 2019) was a Senior United States District Judge of the United States District Court for the Eastern District of Pennsylvania.", "\n\nEducation and career\n\nBorn in Doylestown, Pennsylvania, VanArtsdalen received a Bachelor of Laws form the University of Pennsylvania Law School in 1948. ", "He was in the Canadian Army from 1940 to 1942, and a United States Army Sergeant from 1942 to 1945. ", "He was in private practice in Doylestown from 1948 to 1970, including a period as district attorney for Bucks County, Pennsylvania from 1954 to 1958.", "\n\nFederal judicial service\n\nOn September 10, 1970, President Richard Nixon nominated VanArtsdalen to a new seat on the United States District Court for the Eastern District of Pennsylvania created by 84 Stat. ", "294. ", "VanArtsdalen was confirmed by the United States Senate on October 8, 1970, and received his commission on October 15, 1970. ", "He assumed senior status on October 21, 1985. ", "He died on May 21, 2019, aged 99, after battling leukemia.", "\n\nReferences\n\nSources\n\nExternal links\n\nCategory:1919 births\nCategory:2019 deaths\nCategory:People from Doylestown, Pennsylvania\nCategory:Military personnel from Pennsylvania\nCategory:Deaths from cancer in Pennsylvania\nCategory:Deaths from leukemia\nCategory:County district attorneys in Pennsylvania\nCategory:Judges of the United States District Court for the Eastern District of Pennsylvania\nCategory:United States district court judges appointed by Richard Nixon\nCategory:University of Pennsylvania Law School alumni\nCategory:20th-century American judges" ]

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[ "Q:\n\nIntegral problem, how do I solve?", "\n\n$$\\int_0^a e^{1-2x}\\, dx = \\frac e4$$\nMy problem is solving for $a$ \n\nA:\n\nAnother way to solve it using a change of variable (Even though it is easier to factor out one $e$ of course...):\n$$\nt = 1 -2x \\\\\ndt = -2 dx \\implies dx = \\frac{-dt}{2} \\\\ \nx = 0 \\implies t = 1-2\\cdot 0 = 1\\\\\nx = a \\implies t = 1-2a\n$$\nThen\n$$\n\\int_0^a e^{1-2x} = \\int_1^{1-2a} e^t \\cdot \\frac{-dt}{2} = -\\frac{1}{2} [e^t]^{1-2a}_1 = -\\frac{1}{2} (e^{1-2a}-e)\n$$\nSo you want \n$$\n -\\frac{1}{2} (e^{1-2a}-e) = e/4 \\implies -\\frac{1}{2}(e^{-2a} -1) = 1/4 \\implies e^{-2a} = \\frac{1}{2}\n$$\nTaking log :\n$$\n-2a = -\\ln(2) \\implies a = \\ln(2)/2\n$$\n\n" ]

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[ "Computer Game Development, Design, and Programming\n\nChris Sawyer is the designer and developer behind Transport Tycoon (first published 1994),\n\nthe widely acclaimed RollerCoaster Tycoon game franchise (first published 1999),\n\nand Chris Sawyer's Locomotion (published 2004).", "\n\nLatest News\n\nDecember 22nd 2016\n\nRollerCoaster Tycoon® Classic arrives on iPad, iPhone, and Android devices!", "\n\nThe Original RollerCoaster Sim: Experience all the fun from the original\n\nRollerCoaster Tycoon® and RollerCoaster Tycoon® 2 games,\n\nwith a new app that combines the best elements of Chris Sawyer's classic titles!", "\n\n\n\nOctober 2013\n\nTransport Tycoon now available for iPad, iPhone, and Android devices!", "\n\n\"19 years after the original Transport Tycoon launched for PC, 31X Ltd and the team at Origin8\n\nare thrilled to launch Transport Tycoon on mobile platforms. ", "Bringing in countless\n\ntweaks and improvements over the original, while still maintaining the appeal, depth\n\nand complexity that the fans love, Transport Tycoon on mobile is the greatest\n\nversion of the greatest business simulation game ever made. ", "A uniquely enthralling game\n\nnow releasing on the perfect platform – not only do the new touch screen controls\n\nallow players to reach out and directly influence their business empires, the game genuinely\n\nfeels at home on these devices.\"", "\n\n" ]

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[ "Iatrogenic bismuth poisoning. ", "Case report.", "\nA case of bismuth intoxication following the intraoral use of BIPP-impregnated gauze packs is presented. ", "This report illustrates the need for caution when using potentially toxic compounds in the oral cavity where significant quantities can be absorbed to produce symptoms of poisoning." ]

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[ "Customer reviews of our Baptism and Christening Invitations\n\nMay 4, 2014Perfect design\n\n\"The card was perfect for my daughters christening invite. ", "The paper itself wasn't cheap feeling. ", "It was nice and thick and seemed more expensive then it was.\"", "\n\nMay 30, 2013Simply perfect!", "\n\n\"Absolutely LOVE the quality of this invitation - first time ordering from the Studio Basics line, so I wasn't sure what to expect. ", "The paper itself is a nice card stock, design was simple but elegant and the photo and text print was clear and even better in person. ", "Would definitely recommend.\"", "\n\nMarch 26, 2013Classy and modern\n\n\"I picked this style for my daughter's baptism cuz it wasn't too religious. ", "It's classy and modern. ", "Beautiful impression, thick paper so it doesn't seem cheap. ", "I'm very hands-on, and it was amazingly simple to create this invitation!\"", "\n\nJanuary 27, 2013Excellent quality\n\n\"I used this product for my son's baptism invitation and it was amazing the quality and how easy it was to personalize it. ", "My family kept it as a photo and framed it.\"", "\n\nOctober 29, 2012Just a Beauty\n\n\"The overall rating and quality is A+. ", "My baby's picture turned out so beautiful, it just fits in the card so perfectly. ", "I just changed the font to a bigger size. ", "I am so happy with my baptism invitation from Tiny Prints. ", "I am excited to send it to my family. ", "thank you.\"" ]

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[ "Freezing of tissue-limits for the autoradiographic localization of diffusible substances.", "\nFrozen thin sections and sections from freeze-dried and embedded tissue are used for the autoradiographic localization of diffusible substances at the electron microscope level. ", "The presence of ice crystals in such sections may limit the autoradiographic resolution. ", "Ice crystals are formed during freezing and may grow during subsequent processing of tissue. ", "The contribution of ice crystal growth to the final image was estimated by measuring the distribution of the ice crystal sizes in freeze-etch replicas and in sections from freeze-dried and embedded tissues. ", "A surface layer (10-15 mu) without visible ice crystals was present in both preparations. ", "Beneath this surface layer the diameter of ice crystals increased towards the interior with the same relationship between crystal size and distance from the surface in the freeze-etch preparation as in the freeze-dry preparation. ", "Ice crystal growth occurring during a much longer time during freeze-drying compared to freeze-etching does not significantly contribute to the final image in the electron microscope. ", "The formation of ice crystals during freezing determines to a large extent the image (and therefore the autoradiographic resolution) of freeze-dry preparations and this probably holds also for thin cryosections of which examples are given." ]

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[ "Chicken tortilla soup\n\nHang on a minute. ", "I have to stop laughing and catch my breath. ", "Oh, come on. ", "I’m just kidding. ", "I really am thoughtful, but if Jim reads this post, he might have something to say about the “ever” part.", "\n\nSo anyway, Jim’s been asking for hearty soups for lunch. ", "It’s convenient to make a big pot of soup, then dole it out into single portions and freeze them for another time. ", "At work, he just pops one in the microwave and gets a nice filling lunch. ", "And healthy too.", "\n\nI haven’t made this before, but he really liked it. ", "It’s a bit spicy for me, but if you’d like to do a less spicy version, just use a green pepper instead of the chipotle peppers. ", "Squeezing a little lime juice on at the table really adds a nice touch.", "\n\nHeat olive oil in a large pot over medium heat. ", "Cook onions until translucent. ", "Add garlic and cook another 1-2 minutes. ", "Add the spices (except cilantro) and heat for an additional minute. ", "Next, add cilantro, tomatoes, carrots, peppers, chicken broth, frozen corn, black beans, and shredded chicken. ", "If soup is too thick, add up to 1 c. water to thin it a little. ", "Simmer, partly covered, for 1 hour.", "\n\nWhen ready to serve, place tortilla on baking sheet and broil until brown and crispy. ", "Cool slightly and break into pieces. ", "Ladle soup into bowl, top with tortilla pieces and Mexican blend shredded cheese. ", "Squeeze a wedge of lime over soup just before eating.", "\n\nHa, ha… My husband might question the ‘ever’ part too. ", "I do love him all the time, but sometimes expressing it seems to take a backseat to everything else. ", "Do you think that if I make him this soup I would redeem myself? ;)", "\n\nNice wife! ", "This soup looks lovely. ", "I just made tortilla soup for the very first time recently and have been thinking about it ever since–we just loved it! ", "My recipe is a little different than this but yours looks equally delicious!", "\n\nLOL, I’m not even going to start with you because it would be the “pot calling the kettle black”.", "\n\nThe soup looks great and I love spicy food.", "\n\nHey, Michelle do you have to let the (any)soup defrost some before nuking it? ", "And do you freeze and nuke in plastic? ", "What’s your thoughts on that? ", "I’ve heard & read both are major no-no’s. ", "Thanks!", "\n~ingrid\n\nLonely Scrapbooker – Yea for you! ", "I’m glad you finally made one of my recipes, Diana! : ) ", "And even happier that you like it!", "\n\nIngrid – The plastic container stuff is hard to figure out. ", "I know that some folks say not to reheat in them, but we do anyway. ", "But really just for Jim and me, not for the kids. ", "If I had frozen spaghetti sauce or something that we were all eating, I do transfer that to a pot to reheat it, but for single servings of things like soup, I don’t bother to do that. ", "You’ve got me thinking though, and I’m going to read up on it more. : )" ]

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[ "Cybersecurity firm Kaspersky Lab said a new malware named Duqu 2.0 was used to target Iran nuclear talks venues\n\nA leading cybersecurity firm claims several venues for international negotiations over Iran's nuclear programme have been targeted by a surveillance virus, reportedly linked to Israeli intelligence.", "\n\nKaspersky Lab ZAO said it discovered several of its own internal systems had been infected by highly sophisticated malicious malware earlier this year.", "\n\nAs the company researchers set off to investigate the cyber-attack, they found out that the same virus had been used to infiltrate a series of other targets in the West and the Middle East, including, most notably, hotels where the Iranian delegates met with the P5+1 group to discuss Tehran nuclear ambitions.", "\n\nKaspersky, a Moscow-based firm, said the \"highly sophisticated\" malware platform was a developed version of Duqu, which it described as \"one of the most skilled, mysterious and powerful threat actors in the APT [advanced persistent threat] world\".", "\n\nIt added that the level of complexity of Duqu 2.0 was so high that they believe its use could only be part of \"a nation-state-sponsored campaign.\"", "\n\n\"The people behind Duqu are one of the most skilled and powerful APT groups and they did everything possible to try to stay under the radar,\" said Costin Raiu, Director of Kaspersky Lab's Global Research & Analysis Team.", "\n\n\"This highly sophisticated attack used up to three zero-day exploits, which is very impressive – the costs must have been very high.\"", "\n\nThe firm added that perpetrators were confident they could act with impunity as the high-quality of Duqu 2.0 would let their activity go unnoticed.", "\n\n\"To stay hidden, the malware resides only in kernel memory, so anti-malware solutions might have problems detecting it. ", "It also doesn't directly connect to a command-and-control server to receive instructions. ", "Instead, the attackers infect network gateways and firewalls by installing malicious drivers that proxy all traffic from the internal network to the attackers' command and control servers,\" explained Raiu.", "\n\nKaspersky didn't name Israel as a suspect but the previous version of Duqu was very similar to the infamous Stuxnet worm, believed to have been developed by the US and Israel.", "\n\nIsrael has long opposed the nuclear talks, as it considered a positive outcome could have greatly increased Tehran's threats to Israel's security. ", "Disagreement on the issue also dragged Israel-US relations to a record low.", "\n\nIn March, Washington directly accused Israeli spies of having snooped on the talks to gather intelligence used to fuel opposition to the nuclear deal in the US congress.", "\n\nKaspersky's revelation that venues where the 'P5+1' group met their Iranian governments were targeted is likely to substantiate the claim.", "\n\nThe company didn't identify the hotels and said the attack on its own internal systems was primarily aimed at acquire information \"on the company's newest technologies\".", "\n\n\"Kaspersky Lab is confident that its clients and partners are safe and that there is no impact on the company's products, technologies and services,\" the firm said in a statement.", "\n\nDuqu was a sophisticated piece of malware discovered in 2011 having been used in a number of intelligence-gathering attacks against a range of industrial targets. ", "It had a number of similarities to the infamous Stuxnet worm, leading many to believe it was developed by the US and Israel.", "\n\nDuqu 2.0 is an evolution of the original malware and is believed to have been created by the same group of attackers by Symantec, and is once again being used to hit very specific targets including the P5+1 nuclear talks and the events marking the 70th anniversary event of the liberation of Auschwitz-Birkenau.", "\n\nThe highly stealthy malware would have gone completely undetected while gathering a lot of highly sensitive information before uploading that data remotely to command-and-control servers." ]

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[ "Ireland: IRSP members arrested in Waterford\n\nSome disturbing events have been taking place in the south\nof Ireland, where two IRSP members have been arrested and are being held under\nthe notorious “section 30”. ", "This is clearly a case of political victimisation\nand should be condemned by all socialists.", "\n\nThe true nature of the twenty-six county state has reared\nits ugly head as two members of the Irish Republican Socialist Party, 26-year-old John O'Donoghue and\n55-year-old James Butler were arrested for allegedly being part of an\nillegal organisation, the Irish National Liberation Army.", "\n\nBoth men were arrested under the notorious section 30 which\nhas granted the twenty-six county state powers that add up to internment. ", "Both\ncomrades have denied membership of the INLA, but on June 20,and the\nonly evidence against them being the word of one Gardai officer, they were\nremanded in custody none the less.", "\n\nThis bears a frightening reminisce to the days of internment\nof republicans by British imperialism in the six countries during the troubles.", "\nInternment was used as a weapon to smash resistance to British imperialism and\nweaken the movements of the working class in the six counties. ", "It would not be\nthe first time either that internment has been used by the twenty-six county\nstate to stifle the movement of Irish working people.", "\n\nIn the aftermath of the formation of the twenty-six county\nstate hundreds of republicans and socialists were interned in an effort to end\nresistance to both imperialism and capitalism in Ireland, to maintain British\nimperialism's domination of the island. ", "Many leaders were executed. ", "The ruling\nclass will go to any length to maintain its political power, and as socialists\nwe must organise against such detentions and demand the immediate repeal of\nsection 30.", "\n\nRather than an effort to crack down on serious crime as it\nhas been presented, \"operation anvil\" has amounted to no less than an attack on\nthe IRSP by the forces of the Irish ruling class, as was quite rightly\nrecognised by IRSP Ard\nComhairle (executive committee) member Pól Little when he stated:\n\n\"This is clearly an attack on the IRSP as well as radical\npolitical agitation within the 26 Counties. ", "Today we have two individuals who\nface substantial prison terms on the word of a single Gardai officer, all\nbecause of their political orientation.\"", "\n\nThese arrests amount to nothing less than an attack on\nworking class militants in Ireland. ", "The authorities are worried at the recent\ngrowth of the IRSP and the newfound success of its attempts to build a mass\nworking class based movement. ", "One of those arrested had only been a member of\nthe IRSP for a few weeks and yet is allegedly a hardened fighter. ", "Clearly\nrather than trying to fight crime the Gardai are yet again being used to attack\nthe IRSP and prevent the growth of revolutionary socialist ideas in Ireland.", "\n\nYet these attacks will not prevent the growth of\nsocialism in Ireland. ", "The Cumman (branch) in Waterford that these two arrested\nmen belong to is a recent addition to the IRSP. ", "The Irish working class has\nlong struggled against bitter repression both from the twenty-six county state\nand British imperialism. ", "These arrests are a naked display of the brutality of\nthe ruling class in Ireland and expose that their real interests lie in\nmaintaining the status quo; they will continue to act as the gatekeepers of\nBritish imperialism. ", "In the long run interment merely increases resentment and\ndestroys any illusions that there exists any real form of democracy or free\npolitical association in Ireland.", "\n\nAs internationalists we must oppose this political\nrepression and join the fight for the freedom of these Irish comrades.", "\n\n- For the\nimmediate release without charge of John O'Donoghue and James Butler." ]

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[ "Effect of two cleaning processes for bone allografts on gentamicin impregnation and in vitro antibiotic release.", "\nBone allografts are a useful and sometimes indispensable tool for the surgeon to repair bone defects. ", "Microbial contamination is a major reason for discarding allografts from bone banks. ", "To improve the number of safe allografts, we suggest chemical cleaning of the grafts followed by antibiotic impregnation. ", "Comparison of two chemical cleaning processes for bone allografts aiming for antibiotic impregnation and consequently delivery rates in vitro. ", "Bone chips of 5-10 mm were prepared from human femoral heads. ", "Two cleaning methods (cleaning A and cleaning B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and biological detergent were carried out and compared. ", "After the cleaning processes, the bone chips were impregnated with gentamicin. ", "Bacillus subtilis bioassay was used to determine the gentamicin release after intervals of 1-7 days. ", "Differences were compared with non-parametric Mann-Whitney U tests. ", "The zones of inhibition obtained from the bone grafts cleaned with both cleaning processes were similar between the groups. ", "The concentration of the released antibiotic was decreasing gradually over time, following a similar pattern for both groups. ", "The cleaning procedure A as well as the cleaning procedure B for bone allografts allowed the impregnation with gentamicin powder in the same concentrations in both groups. ", "The delivery of gentamicin was similar for both groups. ", "Both cleaning procedures were easy to be carried out, making them suitable for routine use at the bone banks." ]

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[ "Pro-inflammatory cytokine, matrix metalloproteinases and TIMP-1 are involved in wound healing after mastectomy in invasive breast cancer patients.", "\nMastectomy provides a good model to study the wound healing process after surgery. ", "The involved factors include selectins, pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinases (MMPs), and their natural inhibitors (TIMPs). ", "In the present study, we observed the kinetic changes of these factors in the process of wound healing after a mastectomy, and analyzed the relationship between these factors and the clinical outcomes. ", "Twenty-nine patients, who received a modified radical mastectomy, were recruited to this study. ", "The wound was inspected daily for the presence of flap necrosis, infection and seroma. ", "Drain fluid was collected on days 1, 2 and 5. ", "IL-6, P-selectin, MMP-2, 3, 9 and TIMP-1 were screened by ELISA kits for their impacts on wound healing after mastectomy. ", "IL-6 demonstrated the highest level on Day 1 after operation and was negatively correlated with MMP-2, which in turn showed a consistently negative correlation with MMP-9 for days 1, 2 and 5. ", "Incidences of seroma formation and skin flap necrosis were 27.6% and 20.7%, respectively. ", "Seroma formation was associated with low MMP-2 levels on Day 5. ", "While skin flap necrosis seemed to correlate with high MMP-2 levels and low levels of MMP-9 and TIMP-1. ", "IL-6, P-selectin, MMP-2, MMP-3, MMP-9 and TIMP-1 are important in the process of wound healing after mastectomy. ", "A low MMP-2 level correlates with the formation of seroma, while MMP-2, MMP-9 and TIMP-1 are associated with skin flap necrosis." ]

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[ "Shopping to hire Writers? ", "Here’s Almost everything It’s good to Know. ", "It is fairly clear which you will ideally employ a writer. ", "But where does one get started with?", "\n\nPosted on April 23, 2016 by Christie in Uncategorized | Comments Off on Shopping to hire Writers? ", "Here’s Almost everything It’s good to Know. ", "It is fairly clear which you will ideally employ a writer. ", "But where does one get started with?", "\n\nFunctioning a business with the electronic age demands an enormous quantity of creating.", "\n\nThere’s your internet site . ", "Your blog page . ", "Social media posts. ", "Sales and profits duplicate. ", "Ads. ", "Guest posts. ", "The record goes on. ", "Who’s going to do all of that crafting?", "\n\nAnd there is further. ", "There is search term analysis, internet search engine optimization (Web optimization), enhancing, publishing, and distribution. ", "Are you intending to acquire 15 or 20 hrs outside of your week to accomplish all of that ? ", "It appears not likely. ", "Just what exactly are you currently going to do ?", "\n\nSetting up top-notch duplicate is extremely troublesome. ", "A good number of of our personal web page posts acquire 5 or maybe more hours to write, edit, and publish. ", "Executing that on your own three times each week signifies fifteen hours of the time is gone. ", "That’s time which could be used promoting, producing connections, or building up your workforce .", "\n\nAnd that is specifically why make sure you use a author.", "\n\nMore goes in to the subject material advertising method. ", "Search term examine, strategizing, executing Seo, distributing your posts, and constructing one way links normally takes effort and time. ", "Does one have time for all of that? ", "And when you need to do, do you think you’re self-confident that you could produce material that’s applicable, valuable, and certainly world-class in good quality ?", "If not, it is time and energy to outsource writing into a skilled professional.", "\n\nWhat using the services of a author can do to your home business\n\nPublishing high-quality, invaluable info provides readers on your web page, displays them the value of your service, and aids convert them into faithful clientele. ", "You feature a thing to them – beneficial intel – and so they give back to you – by getting yourself your goods and services .", "\n\nAnd you simply can in fact measure how priceless that is definitely. ", "We wrote a detailed submit on how we evaluate the ROI of our individual articles and other content advertising to help you do exactly the same.", "\n\nTechniques to rent writers\n\nSince you are aware of where by to search out writers for employ , it is time and energy to seek the services of just one. ", "You might think that you just convey to them the things they need to do, they are doing it , and also you fork out. ", "Regrettably, it’s not that simple. ", "Listed here are a couple reasons why:\n\nUsually there are loads of high-quality writers in existence\n\nNot all writers are knowledgeable about material promotion and Search engine optimization\n\nLoads of writers won’t contain the design or tone you’re wanting for\n\nFortunately, those that go in with this awareness, the procedure is far a lot easier. ", "Freelance marketplaces, like Hubstaff or Upwork, allow you submit your position and invite freelancers to express their desire . ", "Writers then destination a bid relating to the task or mail you a proof of why they’d be a beneficial choice .", "\n\nAfter that, it’s your choice to sort as a result of a (perhaps highly colossal) number of candidates and reduce the listing down to a handful. ", "You are going to really need to look at their profiles, websites , and portfolios. ", "And after that, it’s perfect to obtain them do a test undertaking. ", "This lets you see what type of producing they’ll generate for yourself.", "\n\nAnd after that, ultimately , you could potentially use your author .", "\n\nAll this normally requires time, but getting the most excellent author in your industry is truly worth the investment decision. ", "Especially if you might create a long-term marriage. ", "Never assume that you’ll have a very freelancer create one point methods and be undertaken – in case you find out somebody who does tremendous job, working with them on a regular basis are going to be rather treasured .", "\n\nFollow Us!", "\n\nAbout Us\n\nDestination Imagination (DI) is a non-profit, volunteer-led, cause-driven organization. ", "Our purpose is to inspire and equip students to become the next generation of innovators and leaders. ", "Annually, we offer seven new standards-based Challenges in STEM, Improv, Visual Arts, Service Learning, and Early Learning. ", "Each Challenge is Blog and open-ended and enables student teams to learn and experience the creative process from imagination to innovation." ]

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[ "Q:\n\nHow does Non - local Jumps in C defined in setjmp.h work?", "\n\nThe C Reference Manual, Appendix B describes two functions setjmp and longjmp for something called non-local jumps. ", "Apart from the basic understanding that setjmp saves the state information and longjmp restores the state, I haven't been able to understand the exact flow and use cases for this feature. ", "\nSo, what exactly does this feature accomplish and where is it useful?", "\n\nA:\n\nAs for the control flow: setjmp returns twice, and longjmp never returns. ", "When you call setjmp for the first time, to store the environment, it returns zero, and the when you call longjmp, the control flow passes to return from setjmp with the value provided in the argument.", "\n(Note that setjmp needn't actually be functions; it may well be a macro. ", "longjmp is a function, though.)", "\nUse cases are generally cited as \"error handling\", and \"don't use these functions\".", "\nHere's a little control flow example:\njmp_buf env;\n\nvoid foo()\n{\n longjmp(&env, 10); +---->----+\n} | |\n | |\nint main() (entry)---+ ^ V\n{ | | |\n if(setjmp(&env) == 0) | (= 0) | | (= 10)\n { | ^ |\n foo(); +---->----+ |\n } +---->----+\n else |\n { |\n return 0; +--- (end)\n }\n}\n\nNotes:\n\nYou cannot pass 0 to longjmp. ", "If you do, 1 is returned by setjmp.", "\nYou must not return from the function that called setjmp before the corresponding longjmp. ", "In other words, longjmp must only be called above setjmp in the call stack.", "\n(Thanks to @wildplasser:) You cannot actually store the result of setjmp. ", "If you want to return in several different ways, you can use a switch, though:\nswitch (setjmp(&env))\n{\ncase 0: // first call\ncase 2: // returned from longjmp(&env, 2)\ncase 5: // returned from longjmp(&env, 5)\n// etc.", "\n}\n\n" ]

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[ "Q:\n\nASP.NET Core 2 load conventional routes (routing table) from another class\n\nI'm currently working on an ASP.NET Core 2 application. ", "I configure my middleware in the Startup.cs Configure method. ", "In this Method - Configure - I'm setting my conventional routes as well. (", "I don't need Attribute routing in my application).", "\nThe problem is, as soon as the application is going to grow, the configuration might become a little bit confusing due to the huge amount of code.", "\nNow I try to figure out, how to load the conventional routing table from an external class.", "\nMy current routing table looks very regular like that:\npublic void Configure(IApplicationBuilder app, IHostingEnvironment env)\n{\n app.", "UseStaticFiles();\n\n app.", "UseMvc(routes =>\n {\n routes.", "MapRoute(\n name: \"default\",\n template: \"{controller=Home}/{action=Index}/{id?}\");", "\n });\n}\n\nNow I try to figure out, how to load my routes from another class:\npublic void Configure(IApplicationBuilder app, IHostingEnvironment env)\n{\n app.", "UseStaticFiles();\n\n app.", "UseMvc(routes =>\n {\n // .. I want to load my conventional routes from an external class\n });\n}\n\nI just figured there is a way to create an extension method using the RouteBuilder class, like in this post:\nHow to write a middleware as custom router in asp.net core?", "\nHence, in my Configure method I could simply call something like that:\napp.", "UseMyCoolRouter();\n\nMy problem is, I don't really know how to configre the RouteHandler to process regular requests:\nvar rh = new RouteHandler(context => \n{\n // ... how to configure for regular routes?", "\n});\n\nvar rb = new RouteBuilder(app, rh);\n\nrb.", "MapRoute(name: \"default\", template: \"{controller=Home}/{action=Index}/{id?}\");", "\n\napp.", "UseRouter(rb.", "Build());\n\nWhen I create the RouteBuilder instance without a RouteHandler:\nvar rb = new RouteBuilder(app);\n\nI'm only getting an Null reference exception:\n\"A default handler must be set on the IRouteBuilder.\" ", "\nDo you know how I can load my routing table from another class or extension method into my Configure Method in Startup.cs?", "\nThank you very much!!", "\n\nA:\n\nHere is my solution:\npublic class Startup\n{\n //... \n public void Configure(IApplicationBuilder app, IHostingEnvironment env)\n { \n app.", "UseDemoRoutes();\n }\n}\n\npublic static class ApplicationExtensions\n{\n public static IApplicationBuilder UseDemoRoutes(this IApplicationBuilder app)\n {\n app.", "UseMvc(routes => new DemoRouter(routes));\n\n return app;\n }\n}\n\npublic class DemoRouter\n{ \n public DemoRouter(IRouteBuilder routes)\n {\n ConfigureRoutes(routes);\n // ConfigureMoreRoutes(routes);\n }\n\n private void ConfigureRoutes(IRouteBuilder routes)\n {\n routes.", "MapRoute(\n name: \"default\",\n template: \"{controller=Home}/{action=Index}/{id?}\");", "\n }\n}\n\nFirst I created an extension method clean up the Configure method, next I call a class to configure all my routes.", "\nI don't know if it's the best solution, but it works fine... What do you think?", "\nThanks :)\n\n" ]

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[ "jebsonflynn\n\nThe promo-clip is pretty hot (and free!). \"", "straight?\" ", "No. ", "these two clearly know their way around mansex, not super-well (the top rabbit-fucks). ", "The bottom clearly loves cock up the ass. ", "Not criticizing, it's still hot.", "\n\nhotmestizo\n\nMore of Chris Please unmasked? ", "Chris is so terribly hot that he should do more videos. ", "Chris is the guy/man that every man gay or straight would love ho have sex with.or can turn straight guy into bi just for him.", "This guy has an oozing animal sex appeal, and no one can deny and refuse,We look forward seeing more of Chris masked or unmasked.", "\n\nlikmbig\n\nThis is pretty hot, but COME ON with the \"straight stuff\"!!! ", "The guy with the beard has both nipples pierced and rides the other guy's cock like a pro; besides if they really WERE \"straight\" they're not any more: THEY KISSED!!! ", "ha ha-" ]

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[ "Later That Day\n\nLater That Day (stylized as Later That Day...) is the debut solo studio album by Lyrics Born. ", "It was released on Quannum Projects in 2003. ", "It peaked at number 40 on the Billboard Independent Albums chart.", "\n\nCritical reception\n\nSpence D. of IGN gave the album a 9.0 out of 10, saying, \"this is much more than a standard rap/hip-hop album, being more in tune with the bugged out aural manifestations of George Clinton and Frank Zappa than anything else.\" ", "Barry Walters of Rolling Stone gave the album 3.5 stars out of 5, calling it \"the rare hip-hop album that's as free and fun as it is tight.\"", "\n\nTrack listing\n\nCharts\n\nReferences\n\nExternal links\n \n\nCategory:2003 debut albums\nCategory:Lyrics Born albums\nCategory:Quannum Projects albums" ]

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[ "Sunday, March 21, 2010\n\nMoth sought out, even demanded, assignments in conflict zones. ", "She barely survived being shot in the face in Sarajevo in 1992, only to go back as soon as she was physically able. ", "The multiple reconstructive surgeries that followed, as well as the hepatitis C she contracted from a consequent blood transfusion, were mere obstacles she moved around.", "\n\nBut more than three years after being diagnosed with colon cancer, her tremendous life journey has come to an end.", "\n\nMoth, known for her gutsiness, striking appearance, distinctive humor and sense of fun, died early Sunday in Rochester, Minnesota. ", "She was 59. ", "READ THE REST\n\nIn the 1980s she came to the US after reportedly being New Zealand's first camerawoman and started working at KHOU 11 in Houston. ", "She supposedly worked there for about seven years before going to CNN." ]

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[ "Q:\n\nHow to create a function which packs function and arguments into an anonymous function\n\nWith this code:\nfunction printStuff(thing1, thing2) {\n console.log(thing1);\n console.log(thing2); \n };\n\n function callWith(func, args) {\n return function () {\n func.apply(this, args);\n };\n }\n\n function callWith2() {\n theFunc = arguments[0];\n theArgs = arguments.slice(1);\n return function() {\n theFunc.apply(this, theArgs);\n };\n };\n\n x = callWith(printStuff, [\"apples\", \"cheese\"]);\n x();\n\n y = callWith2(printStuff, \"apples\", \"cheese\");\n y();\n\n...why is it that using callWith works but using callWith2 throws an error?", "\nIs there any way to achieve this functionality (namely, a function which takes a function as its first argument and an arbitrary number of other arguments(NOT as a list), and feeds those arguments into the function argument to create an anonymous function it returns)?", "\n\nA:\n\narguments isn't a real array, but an object with numeric keys, a pseudo-array. ", "You need to convert it to a real array to slice it, by calling the slice method of an array, with the arguments as context:\ntheArgs = [].slice.call(arguments, 1)\n\nYou may want to create a toArray helper:\nvar toArray = Array.call.bind([].slice)\n\nNow you can do:\ntheArgs = toArray(arguments).slice(1)\n\n" ]

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[ "Archive for September 2012\n\nA friend of 30 years asked me, “is the Democratic party representing people of faith?”", "\n\nRather than taking offense, because I know he meant none, this was my response.", "\n\nI’m fairly sure there are many people of faith in Jehovah in both Rep & Dem parties, as well as in neither of those parties. ", "I don’t spend any time thinking about that and I’m fine with separation of church and state continuing to be a distinctive feature of the USA.", "\n\nLIke I said before, “4) If your opinion can’t stand on it’s on Grace & Sanity then invoking God doesn’t help your case”. ", "Said a different way, when discussing faith I also would not spend part of that conversation asking who someone voted for in the last election. ", "Said one more way, I’ve known lots of people with whom I share faith and absolutely do not share politics and vice versa.", "\n\nYes I care, but no I do not think either discussion is enhanced by mixing it with the other; which I also think is consistent with the intentions of our Constitutional Founders.", "\n\nThis post was inspided by a political conversation on the Facebook page of my friend Joe Few. ", "If I could offer a direct link I would and encourage you to go read the conversation. ", "It’s a far more sane and graceful discussion than I see most days on Facebook.", "\n\nand now for my opinion:\n\n1) Do I feel better-off than 4 years ago? ", "No, but I didn’t expect to. ", "Wars, fraud and living beyond our means for many years will take a very long time to correct if ever. ", "Honestly I have my doubts because most of the people I see around me continue to live beyond their means.", "\n\nCome on folks, this question is offensive and simple-minded.", "\n\nIn many ways I do of course feel better-off; less war, some fraud corrected, less fear of my government (VP Cheney frightened me), some hard work and some good fortune.", "\n\n2) Money vs Social Grace; don’t ask me to pick ONE; not an option. ", "Does anyone really think we can ask the poor to wait while we argue about the banks, government and ecconomy? ", "Of course not. ", "Of course I hate to see charitable resouces wasted or misused, but I still give and try to lend a hand.", "\n\n3) If you want me to consider your opinion then show some respect; say President Obama (not Mr). ", "If I need to explain this then please don’t leave a comment or follow me on Facebook or Twitter.", "\n\n5) If you think I’m stupid for my opinions … well … YOU’RE STUPID! :-) ", "Seriously all of my political positions are negotiable and adjustable. ", "I love getting smarter so please feel free to offer me constuctive opinions and sources.", "\n\nfyi: I am a loving lucky father and spouse and man of strong faith; neither of these are negotiable. ", "I also am a proud voting citizen, work for a giant global corporation (sometimes evil, mostly not) and have been self employed many times.", "\n\nAt this time I plan to vote for President Obama again; still negotiable." ]

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[ "EMP denial\n\nOn Monday, May 11th, we had a surge of power through our house so great, that it magnified the brightness of our lightbulbs tenfold. ", "The lights and one of the circuits proceeded to burn out, and the surge fried anything that was plugged in—as a strong burst of magnetic energy would. ", "Even a surge strip did not keep the cable box from being fried. ", "This type of situation has never occurred in our home in over 50 years. ", "The event occurred at a little after 13:00 pm CST, or 18:00 UTC. ", "No source was found for the surge, only a fried wire, which had caused a burning smell in the home. ", "Certainly a malfunctioning wire, more than like fried by the surge as well, would not cause a surge in power, but a reduction in it. ", "Would the Zetas care to comment on whether we are now experiencing EMPs from PX on a more frequent basis? ", "If so, would it be recommended that all electronics not in use be disconnected from their power source? ", "Space was relatively quiet, but the magnetosphere was fluctuating widely. [", "and from another]http://www.manchestereveningnews.co.uk/news/greater-manchester-news... The cut was said to have been caused by an electrical surge. ", "People in the area say \"Smoke was coming from the electric cupboard from 86 Deansgate when the power surge hit. ", "4 fire engines responded to the call\". ", "Jade Barrow is a receptionist at 86 Deansgate, and said the whole building shook. ", "She said: \"The firemen explained to me that an electrical surge is like 2 magnets hitting each other. ", "That's why it all shook because of the force.\" [", "and from another]http://poleshift.ning.com/profiles/blog/show?id=3863141%3ABlogPost%... May 15. ", "After 15 days with approximately 300 hours of missing data, it appears the uninterrupted BATSRUS RCM image feed has resumed.", "\n\nAir France 447 in 2009 and Malaysia 370 and the recent Germanwings A320 are in the news because they impact the airline industry, and the blame thus placed elsewhere. ", "To date, pilot suicide, storms, and bad pilot judgement have been used, and how is the public to know otherwise? ", "Electric trains such as the Disney Monorail and DC Metro crash incidents in 2009 and the recent Amtrak 188 go into investigation while talking heads murmur about safety devices or track maintenance or mechanical failure, which ultimately get the blame.", "\n\nIt is only when the public is broadly affected that the public can get a hint that something else is afoot. ", "Cell phones are regularly having disrupted service but the blame is placed on blocked access to towers or bad weather. ", "The blackberry outage in 2008 was blamed on a software glitch. ", "If the public is frankly being lied to, engineers responsible for maintaining equipment and the grid are not fooled. ", "The talk has spilled over into the press, or into conversations with the public. ", "During the Washington DC blackout, the electrical problem was described at first by the Washington Post as a “surge”.", "\n\nThis is a key determinant between a failed electrical system, a simple outage, and electro-magnetic pulse. ", "Pulse is a surge, and the sudden increase in the amount of magnetons and their associated electrons, such that equipment controlled by a steady pace of either particle flow goes into a runaway state. ", "When equipment is guarded by surge protection, to guard against lightning strikes, it will shut down, as a brownout situation can damage equipment. ", "But unless a lightning strike was present, there can be no excuse for a pulse or surge other than the presence of the charged tail of Planet X, aka Nibiru.", "\n\nWhat can the public expect? ", "As cell phone service and cable TV via satellite continues to degrade, as airplanes increasingly crash during complete electronics failure or are forced to land with smoke in their cockpits, as electric trains surge off the tracks and brakes fail, as transformers explode at dams and on the grid, and as residential lights flicker and erratic and unexplained and spotty blackouts descend, the public can expect endless inane excuses from the establishment. ", "The truth will be withheld because mankind is so dependent upon his electrical systems and equipment that the thought of being without is unthinkable. ", "It is mass denial.", "\n\nPower Failure in Brooklyn Shuts Down Subways\n\nSubway service between Brooklyn and downtown Manhattan ground to a halt on Sunday (Sept 17) after a transformer near Jay Street briefly failed, according to the power company.", "\n\nThe temporary power fluctuation, which began around 1 p.m., scrambled train signals and disrupted service on the A, C, E, F and G lines. ", "The shutdown had a ripple effect up several subway lines, resulting in packed platforms and delayed trains from Brooklyn all the way into Upper Manhattan and even the Bronx.", "\n\n“Complete chaos at 145th Street due to an outage in Brooklyn?” ", "a rider named Micah Bergdale posted on Twitter with a picture of a packed platform at 145th Street. “", "This is nuts. ", "People rely on subway for their weekend jobs too.”", "\n\nFor residents of the affected area lights may have dimmed, but the trains were more profoundly affected because a failed transformer can shut down the subway’s signals, said Michael Clendenin, a spokesman for Consolidated Edison, the power company.", "\n\nBy 3 p.m. the issue had been resolved, though officials had not yet determined exactly what caused power failure.", "\n\nOn Thursday, debris, a switch problem and a power malfunctioncaused subway delays in Brooklyn, Manhattan and Queens during the morning rush.", "\n\nPower Outage Causes Subway Chaos On A, C, F And G Trains\n\n\"..A Con Ed spokesperson told Gothamist that there was a transmission disturbance that caused electrical damage to equipment in a substation that serves Downtown Brooklyn. ", "Crews are investigating the incident, which caused a voltage dip that then impacted subway signals, and are attempting to restore service. ", "While there wasn't a widespread power outage due to the substation issue, the spokesperson said some nearby buildings lost elevator service.", "\n\nPower Station Explosion as Outages Sock Colton\n\n(Watch recorded video of a live broadcast Thursday (Aug 31) as Transformers at Substation explodes and catches fire and startles TV newscaster Tony Shin reports for the NBC4 News at 5 p.m. on Thursday, August 31, 2017. )", "\n\nIn the middle of a power outage during a scorching California heat wave, a substation was hit with a blast,\n\npossibly from a power surge or static electricity in the air.", "\n\n~\n\n(The report of Lightning seems to contradict what the live video shows..)\n\nStructure Fire at NV Energy Plant in Zephyr Cove; Thousands Without Power\n\nTahoe Douglas Fire says a mechanical failure likely led to a fire at the NV Energy plant in Zephyr Cove. ", "NV Energy says about 5,300 customers are without power.", "\n\nLiberty Utilities says power has been restored to about 15,000 customers in the South Lake Tahoe, Markleeville area.", "\n\nFire crews say the mechanical failure occurred at the substation off of Sewer Plant Road and caused an outage into the Minden-Gardnerville area.", "\n\nNV Energy says the power went out after 8:30 a.m. on Monday. ", "Tahoe Douglas Fire says NV Energy is working to re-route power to those affected. ", "It estimates that power should be restored by 4 p.m. for most areas.", "\n\nTahoe Douglas Fire says the Kingsbury backup transmission line is under construction and the Glenbrook backup transmission line was damaged in the Carson Fire...\"\n\nSTATELINE, Nev. (AP) — A small fire at an NV Energy substation has triggered a power outage affecting several thousand customers around Lake Tahoe.", "\n\nMore than 15,000 residential and business customers served by NV Energy and Liberty Utilities were without power at one point after the outage was reported shortly after 8 a.m. Monday at the substation near Markleeville, California...\"\n\nSt. Lucia-bound JetBlue plane makes emergency landing\n\n(AVIATION INSPECTOR) – An airliner was yesterday (Aug 26) forced to divert to Bermuda after smoke was spotted coming from the rear of the plane.", "\n\nThe JetBlue flight bound for St Lucia with more than 200 passengers on board made an emergency landing at the island’s airport.", "\n\nA spokeswoman for the Bermuda Fire & Rescue service said the Airbus A320 aircraft was carrying 202 passengers and landed safely in Bermuda at about 12.15pm.", "\n\nShe added: “BFRS personnel dressed in breathing apparatus carried out a thorough search of the airbus compartment with thermal imaging equipment before turning the scene over to the airline representatives.”", "\n\nNo injuries after smoke condition in cabin\n\nLAKE CLEAR — A small passenger plane made an emergency landing at the Adirondack Regional Airport early Friday evening (Aug 25).", "\n\nThe Saranac Lake Volunteer Fire Department responded to a call at the airport at 5:02 p.m. to respond for an emergency landing of a Cape Air passenger aircraft that they were told was experiencing smoke in the cabin.", "\n\nSpeaking Sunday morning, Cape Air spokeswoman Michelle Haynes said there were five passengers on board the nine-person Cessna 402, Flight 1815, which landed without incident at Adirondack Regional Airport. ", "Haynes and firefighters added that there were no injuries and minimal effects to passengers.", "\n\n“In flight, the captain noticed there was an abnormality with the engine,” Haynes said. “", "Definitely something concerning the pilot.", "\n\n“I talked to the station manager in Saranac Lake,” Haynes added. “", "She said the passengers were all fine, they weren’t even aware why they landed.", "\n\n“There was a whiff of smoke,” Haynes continued, “and when the captain adjusted the controls, the smoke immediately dissipated and he called for a priority landing.”", "\n\nThe plane departed from Albany International Airport with a destination of Ogdensburg Regional Airport earlier Friday afternoon. ", "After the emergency landing, firefighters subsequently assisted passengers on the airport runway. ", "Haynes said passengers were then ground transported to Ogdensburg.", "\n\nFirefighters said early Friday evening the cause of the smoke appeared to be the overheating of electrical equipment, though firefighters couldn’t say that with 100 percent certainty. ", "Haynes emphasized on Sunday that the airline still did not know the cause of the smoke...\"\n\nThe blackout occurred at 5.40am on Wednesday, mainly in the city of Suita in central Osaka [Japan]. ", "Some 29,520 homes were affected in Suita, with the rest in the neighbouring Higashiyodogawa ward and Settsu city.", "\n\nPower was fully restored in affected areas in Osaka before 5pm on Wednesday, nearly 12 hours after a major blackout struck at dawn, which cut off power to 34,000 homes and shut down hospitals and 24-hour convenience stores.", "\n\nThe Osaka Police Department said police reports have been lodged of a loud boom occurring underground near the Takakijo district in Suita seconds before power was shut off. ", "A manhole cover was also reportedly dislodged." ]

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[ "Gustavo Cruz\n\nGustavo Cruz (born 21 June 1966) is a former Nicaraguan boxer. ", "He competed in the men's bantamweight event at the 1984 Summer Olympics. ", "At the 1984 Summer Olympics, he lost to Star Zulu of Zambia. ", "Cruz also represented Nicaragua at the 1991 Pan American Games.", "\n\nReferences\n\nCategory:1966 births\nCategory:Living people\nCategory:Nicaraguan male boxers\nCategory:Olympic boxers of Nicaragua\nCategory:Boxers at the 1984 Summer Olympics\nCategory:Pan American Games competitors for Nicaragua\nCategory:Boxers at the 1991 Pan American Games\nCategory:Place of birth missing (living people)" ]

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[ "In vivo immunosuppressive effects of recombinant ovine interferon-tau (trophoblastin): r.oTP (r.oIFN-tau) inhibits local GVH reaction in mice (PLN assay), prevents fetal resorptions, and favors embryo survival and implantation in the CBA/J x DBA/2 mice combination.", "\nOvine trophoblastin protein, be it natural or recombinant (oTP,r.oTP), a member of the tau interferon family (r.oIFN-tau), has been shown to possess immunosuppressive properties in vitro. ", "It acts as a cytostatic agent across species. ", "Indeed, it was immunosuppressive when tested on human and murine lymphocytes in a variety of in vitro immune assays, as it is also on syngenic (ovine) lymphocytes. ", "In the present paper, we first verified that this property to act across species also occurred in vivo assays; r.oTP was able to down regulate a local GVH reaction assay (PLN assay) in mice. ", "We then took advantage of these properties of r.oTP to investigate its in vivo effects during murine pregnancy as there is no ovine equivalent of the murine CBA/J x DBA/2 resorption prone mating combination. ", "When given in the postimplantation period, r.oTP drastically boosted resorptions in the CBA/J x DBA/2 matings, as did murine recombinant gamma interferon. ", "However, the same r.oTP treatment in the peri-implantation period resulted in a reduction in resorptions in this spontaneous abortion system. ", "The data suggested that r.oTP might have acted more by favouring implantation and embryo survival than by preventing the resorption process itself. ", "The mechanisms possibly underlying these effects, as well as the putative uses of r.oTP evolving from these data, are discussed." ]

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[ "Few would disagree with Ms Jaya Anil Kumar, a case manager for the Humanitarian Organisation for Migration Economics, who said that live-in helpers are inherently vulnerable to exploitation and abuse (When family members abuse a maid together, Sept 9).", "\n\nBut are employers not vulnerable too (Maid abuse? ", "What about the reverse? ", "Sept 16)?", "\n\nHaving, out of necessity, to admit a stranger - not knowing her mental state, and cultural beliefs and practices - into one's home, affecting one's privacy and changing the home's dynamics and equilibrium, is daunting.", "\n\nWe must avoid demonising and treating employers as potential villains. ", "What is needed is managing the expectations of both parties - the employers and the foreign domestic workers (FDWs).", "\n\nAn accurate and truthful biodata of an FDW is a good starting point. ", "A lot of tension and frustration arise when an FDW cannot perform tasks that she claims she can in her biodata.", "\n\nIt does not help when FDWs are encouraged to dress up their profiles and capabilities by lying.", "\n\nLying is a bad start, but FDWs tend to do this throughout their entire employment journey, believing that it ensures survival.", "\n\nEvery job, even the most lowly, has a set of key performance indicators (KPIs). ", "In working life, a worker who falls short of his KPIs is subjected to reprimand, counselling, forgone bonus, promotion freeze, and even dismissal.", "\n\nFDWs cannot be treated differently. ", "If they underperform, lie, or have a negative work attitude, they must be prepared for counselling and scolding. ", "This should be emphasised during the settling-in programme.", "\n\nUltimately, we want a fruitful, understanding and happy employer-FDW relationship. ", "This is achievable only through having a fair and equitable framework set up by all stakeholders - employers, FDWs, the Ministry of Manpower, host country governments, migrant workers' rights groups, and recruitment and employment agencies.", "\n\nUltimately, we want a fruitful, understanding and happy employer-FDW relationship. ", "This is achievable only through having a fair and equitable framework set up by all stakeholders - employers, FDWs, the Ministry of Manpower, host country governments, migrant workers' rights groups, and recruitment and employment agencies.", "\n\nThe employer-FDW framework is a work in progress. ", "A lot more needs to be done to strengthen it.", "\n\nLawrence Loh Kiah Muan" ]

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[ "EA look back at the origins of Syndicate\n\nStarbreeze Studios new title is a far cry from the original game and this trailer should bring back memeories for those old enough to remember. ", "Syndicate was an absolute classic when it was released way back in 1993, it really got you hooked. ", "It was fun, innovative and looked great at the time. ", "Watching this trailer now it highlights how far games have come since the early nineties but it does bring back fond memories of countless hours spent waging war against other syndicates on my 486 SX25. ", "The plan with the new title is to rekindle some of the original game’s magic, although I have to say the new game appears to be pretty far removed from the original vision, even if the plot is similar. [", "video2=2526]" ]

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[ "Responses to acute exercise in type 2 diabetes, with an emphasis on metabolism and interaction with oral hypoglycemic agents and food intake.", "\nIn people with type 1 diabetes mellitis (DM), insulin administration, food intake, and exercise have to be carefully matched to avoid either hypo- or hyperglycemia. ", "People with type 2 DM have some insulin secretion, which changes with needs. ", "Accordingly, during exercise, these people do not run the same metabolic risks as people with type 1 DM. ", "However, a contraction-mediated increase in glucose clearance in muscle is intact in type 2 DM. ", "Therefore, in the postabsorptive state in diet-treated type 2 DM, a marked reduction in hyperglycemia can occur during prolonged moderate exercise. ", "Sulfonylurea drugs augment the rate of decline in plasma glucose, because stimulation of insulin secretion reduces hepatic glucose production. ", "After abstention from sulfonylurea for 5 days, the rate of decrease in plasma glucose with exercise is also enhanced, but from a higher glucose level. ", "In the postabsorptive state, brief vigourous exercise elicits an increase in plasma glucose concentration, reflecting an exaggerated counterregulatory hormone response and glucose production. ", "Moreover, insulin sensitivity is reduced in the early postexercise period. ", "In the postprandial state, both prolonged moderate exercise and intermittent high-intensity exercise markedly decrease meal-induced increases in glucose, insulin, and C-peptide concentrations, whereas glucose appearance in plasma is unchanged. ", "When exercise bouts are isocaloric, responses are identical, indicating that overall energy expenditure, and not peak exercise intensity, is the major determinant of exercise-induced changes in overall glucose homeostasis and insulin secretion in type 2 DM. ", "Neither prolonged moderate nor intermittent high-intensity exercise performed in the postprandial state influences glucose or insulin responses to a subsequent meal. ", "Finally, in people with type 2 DM, after a high-fat meal, prolonged moderate exercise reduces the exaggerated increases in plasma concentrations of triglycerides contained in chylomicrons and very low-density lipoproteins." ]

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[ "Max Bupa Network Hospitals in Bhubaneshwar\n\nSelect Insurer\n\nSelect State\n\nSelect City\n\nOverview of Max Bupa Network Hospitals\n\nBhubaneswar, the capital of Orissa, is also popularly known as the \"Temple City of India”. ", "Bhubaneswar has all types of entertainment like beaches, waterfalls, lakes, parks and gardens along with zoos are important places that visitors need to visit. ", "Many great educational institutions are built here for the youth here and to develop the city and the state into a modern city.", "\n\nThere are various hospitals and clinics in Bhubaneswar, which are offering medical facilities to people from nearby states also. ", "The city has various ayurvedic centers that provide consultation and treatment. ", "Max Bupa has joined hands with various hospitals and clinics in Bhubaneswar to offer cashless hospitalization to its policyholders. ", "It means, you can avail treatment at any of these hospitals and Max Bupa will bear your medical expenses." ]

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[ "September 7, 2009\n\nIt seems that Mike Lupica is amusing his readers who want the opposition to shut up. (", "When did \"shut up\" become a liberal argument?)", "\n\nHere's the end of Lupica's shut-up-loons column:\n\nSome of this is racial, though Obama's critics would never see themselves as being racist in a million years.", "\n\nAnd the sense that criticizing the President is racial, is that racial? ", "I'm guessing Mike Lupica wouldn't see himself as being racist in a million years.", "\n\nBut there is something more going on, not just white versus black but white hats versus black hats, on both sides of politics, both the right and left selling conflict with both hands, trying to give you a Civil War every night on Cable America because that's where the ratings are.", "\n\nOnly it's not civil. ", "And somehow the most gullible people have been convinced that the enemy is anybody who disagrees with them. ", "About anything.", "\n\nMaybe the ones who fear Obama the most, the ones who hate him the most, should try doing what a lot of schoolchildren will do tomorrow, as this President tries to inspire them:\n\nAs a change of pace, maybe they should stop shouting and listen.", "\n\nOh, wait! ", "Mike Lupica never wrote the words \"shut up and listen.\" ", "He wrote: \"stop shouting and listen.\"", "\n\nAnd he doesn't call anyone \"loon\" either. ", "But somehow the headline writer read his column and came up with \"Loons should shut up and listen.\"", "\n\nI guess it's not just \"Cable America\" that's \"trying to give us a Civil War\" and \"selling conflict with both hands.\" ", "It's Lupica's newspaper, the Daily News, reading his column that — irony! — ", "calls for civility.", "\n\nOr did the headline writer pick up Lupica's real message, which was not the \"civility\" business padding page 2? ", "The real message is: Obama's opponents are crazy/racist/stupid and should not be talking. ", "And if you protest that characterization you're being uncivil.", "\n\nThe debate about Obama's CRAZY critics has evolved from simple free speech being exercised among some Internet Idiots into free thinking being exercised among the captives of the Old Media's Meme-masters. ", "That sounds like a revolution has been started among a once free people to throw off the shackles of mind control on them that the Old Media had worked so long and hard to develop. ", "Now if a leader that has these free people's trust will stand up and Face Book or something, then the free people may indeed win. ", "It has been a very interesting 6 weeks since Trig Palin's Mom spoke up for him and reminded us that we all, like Trig, deserve to have leaders that care more about our welfare than they care for their own wealth and power.", "\n\nSince when does anyone give a damn about what Lupica has to say about politics? ", "Wait a minute, better get John Madden on the phone as well to get his two cents. ", "For that matter, let's call up Terry Bradshaw and get his take as well. ", "Obviously, Mike Lupica\n\nLovely; the leftist media is up in arms over anyone who dare question their president. ", "Yet, Lupica has the unmitigated gall to describe anyone who dare question our Socialist-In-Chief as having gone \"haywire.\"", "\n\nBetter yet, \"...the most guillible people have been convinced that the enemy is anybody who disagrees with them.\" ", "Of whom are you speaking Mr. Lupica? - ", "clearly that has been the leftist policy line for decades now. ", "Finally, it is your leftist brethren (such as, for instance, the superintendent and school board of Broward County) who are ordering kids to listen to Obama and to \"sit there\" and \"be silent;\" in other words, they must subject themselves to The One, they must sit there and they must shut up.", "\n\nFrankly, Mr. Lupica doesn't even have the ability to formulate sound, objective political commentary. ", "His role is that of a well-trained parrot; he is merely a hack who is towing the policy line of Mort Zuckerman, the darling of MSNBC, publisher of NY Daily News, chairman/editor in chief of US News & World Report and financial contributor to Democrats - who in fact contributed to California Democrat and \"super-delegate\" George Miller (George Miller supported, you guessed it, Obama).", "\n\nI think Obama will do a fine job of regurgitating partially digested mush into the mouths of little schoolchildren. ", "I have no argument with it. ", "I think this is one of a number of things that he does better than Hillary.", "\n\nThe 8:45 AM Call of left-wing groups for officials from more than 20 labor, environmental, and other Democratic-leaning groups dial into a private conference call hosted by two left-leaning Washington organizations. ", "makes sense in a lot of ways. ", "Our allies on the right often do the same.", "\n\nWhat is at fault on the blogs and even sometimes here is the lack of actual thought that goes into a comment. ", "While I personally am on the right on a majority of the hot button issues, I still despise the mindless repetition of talking points, the demonizing of all on the other view side, and the \"case closed\" attitude that comes from anyone of any political stripe.", "\n\nWhat a country! ", "On this Labor Day we can comment here without the fear that we'll be shut down or possible jailed. ", "More than 2/3 of the World's Population can't say that today.", "\n\nMay be sentimental to say it, but thank you Ann for this forum, and God Bless America this Labor Day and for always!", "\n\nThe speech is up, and it is boilerplate and trite. ", "There is no reason any school should be required to carry it. ", "There should be no controversy if a school decides to carry it.", "\n\nIt proves the propaganda attempt made by the Dept of Education, though. ", "To call it \"historic\" or to encourage kids to see it as \"inspiring\" was a serious overreach. ", "The administration was definitely trying to use teachers to encourage students to see this as something other than...boilerplate and trite.", "\n\nIsn't it interesting this idea we have that it's okay for a politician to talk to children as long as he doesn't seem to be political?", "\n\nI don't think piping politicians into the captive audience of classrooms is okay in any case, but if I were arguing that it was okay, I wouldn't argue that it was okay because the politician appeared to be apolitical.", "\n\nA politician's job is to be political. ", "If a fireman comes to school to talk about his work, it's about being a fireman. ", "He doesn't try to tell you about his career while dancing all around his goal to put out fires. ", "A policeman wouldn't come and give a talk that carefully avoided mention of catching criminals.", "\n\nIf a politician is going to talk, it seems more appropriate that he be political.", "\n\nYou're supposed to be engaged with him as your representative. ", "You're not supposed to bond with him as your buddy.", "\n\nAccording to this logic, those protesting against Bush's likely overthrow of the 2008 election (remember how long ago it was? ", "It was like 2 or 3 percentage points lower unemployment and several trillion dollars of borrowing/spending ago. ", "How time flies!) ", "should have just shut up and waited for it to happen, and then they could have protested.", "\n\nThe hilarious thing is that so many of the crowd screaming \"read the bill\" have not even\"read the speech!\" ", "Irony is lost on them. ", "Wankers!", "\n\nThe difference is, the bill actually existed before 35 minutes ago.", "\n\nAs Freeman says, the problem isn't the content and I, like her, never argued it was.", "\n\nThe Department of Education wanted to turn a completely banal speech into a \"historic\" event to encourage children to help the President. ", "Obama supporters tried to make it just horrible if schools didn't want to choose to play the speech.", "\n\nIt has never been, and never should be, a requirement that citizens of any age listen to a president speak. ", "If a school doesn't feel this boring message will help their students, they should be able not to play it without harassment from the likes of Robert Gibbs.", "\n\nSomewhere we've let it creep into our consciousness that our politicians are our betters. ", "They are not -- they are simply selected for a short period of time. ", "They haven't earned the right to be our kings. ", "And they don't have the right either.", "\n\nI realize that deep inside Teh One™ is a desire to make the unpleasant opposition just go away, but really, did we make him take the job? ", "I seem to recall he spent nearly a billion dollars just to get elected, which sounds like he really wanted it.", "\n\nSo he should just put up with the noisy, fact-free opposition. ", "I'm sure he's still quite mad a Troofer got exposed and ejected during this very critical time when all the attention should be about HIM.", "\n\nHere are snippets from Obama's speech that the crazies leading the Republican Party have called \"indoctrination\" and \"socialism.\"", "\n\nAll quotes:\n\n* Whatever you resolve to do, I want you to commit to it. ", "I want you to really work at it.", "\n\n* Every single one of you has something you’re good at. ", "Every single one of you has something to offer. ", "And you have a responsibility to yourself to discover what that is. ", "That’s the opportunity an education can provide.", "\n\n* But at the end of the day, the circumstances of your life – what you look like, where you come from, how much money you have, what you’ve got going on at home – that’s no excuse for neglecting your homework or having a bad attitude. ", "That’s no excuse for talking back to your teacher, or cutting class, or dropping out of school. ", "That’s no excuse for not trying.", "\n\n* No one’s born being good at things, you become good at things through hard work.", "\n\nOK, wingnuts! ", "Show us the socialism you have been screaming about!", "\n\nWhat are you opposed to anyway? - ", "Students showing up to school - Students studying. - ", "Students learning. - ", "Students listening to teachers and parents? - ", "Hard work\n\nWhat, exactly, do you disagree with so much in this speech that you had to raise holy hell about it?", "\n\nFreeman, you are confused. ", "You have no right to speak if you speak against the Anointed One Who Can Do No Wrong Especially When He Usurps the Role of the Parent and Teacher in Order to Speak About Himself.", "\n\nGet with the program. ", "You don't want to be on the losing side, do you? ", "After all, he won, and all dissent must now be silenced, especially icky dissent from people peeking behind the curtain.", "\n\n\"Shut Up\" and do things the stalinist way, is always the liberal's argument position on everything (plus demeaning comments and personal destruction perpetrated against anyone disagreeing with the pure liberal faith). ", "The porkulus bill, cap and trade, the health insurance legislation, global warming, and other issues were all 'shut up' 'don't read the bill' 'republican/ conservative input not wanted' 'vote first don't ask questions afterward' by the democrat-liberal caucus in Congress. ", "When republicans on few occasions tried to exclude democrat input in bills pending before Congress, the liberal media reported it like the republicans were attempting a coup d'etat, but nowadays with nearly forty czars, most of the lamestream liberal media is asleep with visions of Obama giving state run sugarplums, dancing in their heads.", "\n\n\"The Department of Education should not be producing paid political advertising for the president, it should be helping us to produce smarter students,\" said the head of the Florida Republican Party.", "\n\nWhat a loon!", "\n\nOops! ", "That was Dick Gephardt, House Majority Leader (the Steny Hoyer of his time) speaking about Reagan's speech. ", "Of course, when that happened, Dick was right. ", "But this time, to say the same thing is to (a) be a loon and (b) to be a hater of the President.", "\n\nMy, my, my. ", "How things change when there's a (D) instead of an (R).", "\n\nMark, you still there? ", "Because this will be a good stunt for your radio show today.", "\n\n“But at the end of the day, the circumstances of your life – what you look like, where you come from, how much money you have, what you’ve got going on at home – that’s no excuse for neglecting your homework or having a bad attitude. ", "That’s no excuse for talking back to your teacher, or cutting class, or dropping out of school. ", "That’s no excuse for not trying.”", "\n\nSo my take is that this speech is Obama being father to all the kids who are growing up in a home without a father. ", "Because this is all stuff that normally the parents tell their kids; they don’t need the president to tell them. ", "But I applaud the effort if Obama can help 5 kids raise their effort level and believe enough to get out of the poverty trap.", "\n\nBut while he is on this topic, maybe Obama will take the opportunity to apologize to these kids without fathers in their home, for the \"Great Society\" programs that destroyed the black family structure in America, and left so many of these kids without a father to provide and protect them, and read to them and demand that they do their homework.", "\n\nHe could go further and make it a teaching opportunity to explain how it was that well intentioned but misguided rich white liberals cared enough about these kids to throw food stamps at them, but not enough to downgrade from their own penthouses to distribute their own wealth, and not enough to erect social policies that helped keep their family structure in tact and their father at home (the uncontroverted most influential factor in a poor kid’s success.)", "\n\nAs Freeman says, the problem isn't the content and I, like her, never argued it was.", "\n\nThe Department of Education wanted to turn a completely banal speech into a \"historic\" event to encourage children to help the President. ", "Obama supporters tried to make it just horrible if schools didn't want to choose to play the speech.", "\n\nAgreed. ", "It wasn't so much the content of the speech, WHICH by the way we don't know it the santized speech released now is the same as the one that would have been given had they not been caught with their pants down.", "\n\nThe objection is two fold\n\n1. ", "Forcing ALL children or forcing anyone to have to listen to a speech by a politician. ", "This should be a voluntary action as long as we are a free society.", "\n\nand MOST IMPORTANLY\n\n2. ", "Objection to the mandated...oooops I mean suggested....lesson plan following the speech to reinforce the President's message, whatever it was going to be.", "\n\nThis is propoganda pure and simple and indoctrination of a captive group of people. ", "Children. ", "Classic technique used in dictatorships and communist countries. ", "Trying to make the Dear Leader central to the children and make the children more loyal to the Dear Leader than they are to their parents and to their parent's value system. ", "Pure evil and they got caught.", "\n\nThey got caught and the people are are on to them. ", "People are aware of the soft indoctrination that has been taking place in the public school system for years and THIS was the last straw.", "\n\nObama using the first day of school to try to raise education performance by reaching our directly to the educable - pure leadership and service.", "\n\nIf so then why has the most media/web savvy president evah produced such a vapid, static presentation?", "\n\nWhy didn't the WH reach out to the rich resources available in the liberal online and media community to produce a presentation that teachers could build upon?", "\n\nAs to the public outrage, the WH stepped on its own dick by not releasing the speech text when they PR'd the broadcast.", "\n\nUnfortunately, when Obama told Americans who do not support his agenda to stop talking and put a snitch site on the WH server he created a poisonous atmosphere that taints everything he does with suspicion.", "\n\nIt was his choice to alienate half the country. ", "Now he has to live with the fallout.", "\n\nI predict everybody will grab their hats and leave within two sentences.", "\n\nNobody likes being addressed like that.\"", "\n\nagreed. ", "it reads like a cross between a local tv version of Mr Rogers and the blandest ward cleaver lecturing the beav' then tousling his hair.", "\n\nthe most troubling thing to me is his mention of google, twitter and facebook by name. ", "is this the first instance of state-sponsored product placement in a presidential speech?? ", "how is that ok? ", "those companies helped get him elected so i guess he had to pay them back somehow. ", "icky.", "\n\n1) It's wasting school time. ", "Schools already waste time and money, this only adds to it.", "\n\n2) That the department of education is at all involved in writing lesson plans and dictating how instruction is to be done. ", "Even if the lesson plans were totally benign (which the originals were not) this is simply not the function of the federal government. ", "We have a federalist system for a purpose.", "\n\nDo note that I'm also not pleased with how much states involve themselves in the minutia of public education.", "\n\nLike Freeman -- some good things, but over all a waste of time to make kids all over the country sit still and listen on HIS schedule. ", "Not to mention having preK and little kids listen. ", "Say what?", "\n\nAnd definitely a re-write after the flak they got.", "\n\nBut some things can never be sanitized out:\n\nRe miller. ", "This commenter also noticed the wash of *I s* over and over and over...\n\nAforementioned commenter didn't get around to counting all his *I s* because commenter is too busy not being President of the United States of America.", "\n\nDid you know that \"I'm working hard to fix up your classrooms and get you the books, equipment and computers you need to learn.\"", "\n\nBetcha didn't know that! ", "Let me know when you see the POTUS with his hammer and paint brushes. ", "Is he driving the UPS delivery truck? ", "Maybe we should send our Box Tops for Education to the White House to help him?", "\n\nWhy does he friggin have to take credit for every single thing? (", "Because narcissists do not think in the we.)", "\n\nCritics are particularly upset about lesson plans the administration created to accompany the speech. ", "The lesson plans, available online, originally recommended having students \"write letters to themselves about what they can do to help the president.\"", "\n\nThe White House revised the plans Wednesday to say students could \"write letters to themselves about how they can achieve their short-term and long-term education goals.", "\"\"That was inartfully worded, and we corrected it,\" Higginbottom said.", "\n\nSo the administration admits they made a mistake and that the so-called loony critics had a valid complaint.", "\n\nIt was precisely the essay part, not the speech itself, that gave many people like myself, a \"WTF?\" ", "reaction. ", "And that's good. ", "Means people are paying attention.", "\n\nAfter eight years of \"abstinence only\" education is the left so soon to pretend that children AREN'T brainwashed in school?", "\n\nAll children are brainwashed in school and they have always been brainwashed in school. ", "In the 50s children were brain washed about those sneaky homosexuals:\n\nhttp://www.youtube.com/watch?v=ijbovskICjk\n\nSpeaking from my own highschool experience in the late 80s/early 90s, I know I sat through countless “lessons” on the evils of pesticides and the virtues of organic farming (among whatever other environmental issue was hot at the moment). ", "All of it one-sided propaganda.", "\n\nSo these parents are not loons for thinking their children will be brainwashed at school, they are just a little late to the party.", "\n\nBut it has little to do with Obama's address (which is comparatively harmless), and keeping their kids home for one day is a pointless gesture when every other day the kids will be inundated with indoctrination.", "\n\nThe only solution is to either keep your kids home from school every single day, or to teach your children to be skeptics, to question authority, and to have finely-tuned bullshit detectors. ", "And then dare the school system to try to brainwash your kids, having enough faith that your children are not total flakes that will believe everything they hear at school.", "\n\nI’m here I knowI know When I was young I wasn’t too happy I know But I’m here today I have something importantI’m here because I want to talk with youI’ve given a lot of speeches I’ve talked a lot I’ve talked I’ve talked I’ve talked a lot I want to focus\n\nAye yae yae\n\nBut praise be! ", "He does NOT say \"Let me be clear...\" or \"As I have said before...\" Whooee!!", "\n\n\"Don’t be afraid to ask for help when you need it. ", "I do that every day. ", "Asking for help isn’t a sign of weakness, it’s a sign of strength.\"", "\n\n{Therefore I am strong. ", "Kids make connections like that. ", "Propagandists write that way.}", "\n\n\"Your families, your teachers, and I are doing everything we can to make sure you have the education you need to answer these questions.\"", "\n\nHe is doing EVERYTHING? ", "Wow. ", "Whiff of hyperbole there. ", "How about school vouchers? ", "Mmmm? ", "How do those DC kids feel about that? ", "If I were the DC parents and others denied the choice (!) ", "of school vouchers I would jump on that.", "\n\n\"I’m working hard to fix up your classrooms and get you the books, equipment and computers you need to learn. ", "But you’ve got to do your part too. ", "So I expect you to get serious this year. \"", "\n\nBecause *I* said so.", "\n\nWhen there is NO accountability, statements like that are useless, except for those who internalize it as they have a special relationship with whoever the speaker is.", "\n\nOkay -- now that I have trashed it I think it nice to encourage kids. ", "But he really is stuck on being POTUS. ", "And on himself.", "\n\nHow about working with communities with high risk factors in a more low key fashion and not sounding like a nanny. ", "If he thinks they're in love with him because he's the first \"black\" POTUS, he's probably right. ", "They could have managed this a lot better. ", "But they'll have to cut out the personal crap if they don't want marching, dancing and singing kids on youtube that we can freak over.", "\n\nwv = lionaOk. ", "This liona will shut up.", "However -- this is the WRITTEN text. ", "Assuming he doesn't go off TOTUS tomorrow, it should be the same, but I would expect a couple deviations.", "\n\nDBQ - This is propoganda pure and simple and indoctrination of a captive group of people. ", "Children. ", "Classic technique used in dictatorships and communist countries. ", "Trying to make the Dear Leader central to the children and make the children more loyal to the Dear Leader than they are to their parents and to their parent's value system. ", "Pure evil and they got caught.", "\n\nThey got caught and the people are are on to them. ", "People are aware of the soft indoctrination that has been taking place in the public school system for years and THIS was the last straw.", "\n\nDBQ has it right. ", "This is not so much about the words as liberal educrats again setting up a system to push their beliefs on malleable children. ", "It is our liberal educrats taking \"best lessons learned\" from Uncle Adolf and Pappa Joe and the local \"reducation Soviets\" the Bolshevik Jews set up for educating workers and children in \"correct thought\" and applying it here.", "\n\nOrwell understood this.", "\n\nAnd knew that the key to success of \"Dear Leader\" was to say 95% good and unquestionably helpful things, to slip the sinister into reeducation. \"", "Be good students. ", "Work hard. ", "Wash behind your ears. ", "Fight the class enemies that exploit the sweat of honest people and kill THEIR children. ", "Share your cookies, be nice! ", "Take care of your neighbors dogs when he is away doing heroic concrete pours for our new People's dam. ", "Water his flowers..Tell your teacher if your parents have any deviant or counter-revolutionary thoughts, so the commissar can help you..Always shine your shoes. ", "Help a classmate with their math assignment. ", "Remember that your work at harvest time is really good. ", "Each cabbage you pick and trim at children's harvest break will mean a little less hunger for all. ", "Don't pee in the pond - hero proletariate drink from there!\"", "\n\nIn America, the same system, with revised textbooks, has been used to revanche US history into a tale of the Oppressors and the Oppressed. ", "It has been used to excuse crime as an expected social injustice response. ", "And a system of Algore \"The Planet is melting\" curriculum reinforced with teacher lesson plans, grades based on \"level of green activism\" has been used to foster a belief system.", "\n\nPeople are getting very queasy about kids coming out of public school showing manifestations of indoctrination..\"The US was really no different than the Nazis...see what we did to Japanese-Americans!!\" \"", "Mom, you need the new Algore CFL bulbs, because if you don't use them, our family will be complicit in killing polar bears!\" \"", "Meat-eating is bad. ", "My teacher says there are good things to eat, and bad things..like meat, soda, peanuts that can kill people...\"\n\nSo along comes another Leader, on top of Gore, that seeks to make use of the same system in school. ", "And people are concerned. ", "No surprise!", "\n\n\"The Department of Education should not be producing paid political advertising for the president,...\"\n\nAnd the National Endowment for the Arts should not be producing propaganda for the president.", "\n\nAnd AL should reconcile his demand that we \"accept\" the election of Barack Obama by suspending our own ideas about the world and about politics and that we disagree only without making ourselves heard, with the opposition to our previous president who *also* won.", "\n\nAlso, AL, Obama only provided the content of the speech when forced to do so and the DoE guide lines were altered so they no longer had the phrases in them that were most objected to and local schools have received enough push-back from parents to be cautious about what they do.", "\n\nCrowing that the present situation proves that there was no there, there, is like saying that an immunized child who doesn't get sick proves the shot was unnecessary.", "\n\nI am not surprised that Obama's school speach is in the end pretty tame (wash your hands...) but I am also not surprised many do not trust him. ", "Why should they after nonsense like Van Jones resignation being called racism and the MSM ignoring anything critical of Da One?", "\n\nI am not surprised that Obama's school speach is in the end pretty tame\n\nMe either. ", "It would be very interesting to know what the speech was going to say before they got caught. ", "Wouldn't it? ", "Hmmmmmm?", "\n\nNo one trusts Obama or any of the thugs that he is surrounding himself with. ", "He has been caught in too many lies, exagerations and refusals to disclose information. ", "Why would we trust him? ", "Seriously. ", "Give me a reason.", "\n\nVW: REFUNIT what I ask for when I took that faulty hard drive back to Best Buy.", "\n\nHow funny. ", "Now that the speech has been released, and it's obvious that the speech will be the non-partisan, positive (if somewhat bland) speech that Obama's supporters said it would be, the people who were bashing it for days in advance are now mostly talking about how they were never opposed to the substance of the speech, just the process. ", "And of course, you have our local village idiot, Dust Bunny Queen, emerge from her trailer to say, \"It would be very interesting to know what the speech was going to say before they got caught. ", "Wouldn't it? ", "Hmmmmmm?\"", "\n\nHow pathetic. ", "This would all be a good joke, except for the genuine damage being done to this country by the Obama Derangement Syndrome crowd.", "\n\nDo you *really* think this is the same speech? ", "If it's the same speech why not release it when the decision was made to release it instead of days later? ", "And really, did the Department of Education have a copy of the speech in order to write up the proposed lesson plans about helping the President? ", "Or was that just a case of over-zealous public employees acting on their own and making assumptions about what the President would say in his speech to school children.", "\n\nAnd *really* at what point would the creep factor set in for you?", "\n\nWhen the WH has a conference call with artists that receive government grants and asks them to think of ways to use art to promote the president's agenda? ", "Would that be creepy to you? ", "Hamsher over at Firedoglake is on about how anyone who criticizes the administration gets their funding cut. ", "She's a loony lefty. ", "Is she blowing smoke? ", "Would you find it creepy if people within the administration seemed to be directing private organizations to boycott opposition voices? ", "Would you think it *strange* and perhaps a bit disturbing if the administration asked loyalists to send the information on those spreading \"lies\" to a white house snitch line?", "\n\nMaybe you wouldn't. ", "But a whole lot of people genuinely think that the specter of Beloved Leader simu-cast to all the school children in the nation to have reached the point of *creepy.*", "\n\nParticularly when accompanied by prepared lesson plans to direct the children to think of ways to help the president.", "\n\nI *get* that the left doesn't see anything wrong with propaganda and censorship and bright children footsoldiers in the noble crusade... but can't you just *pretend* for a while that these things are creepy? ", "Pretend for form's sake if nothing else, even if no one has the balls to so much as criticize someone like Chavez for shutting down radio and news stations. ", "Seriously WE DON'T TRUST YOU and we don't trust OBAMA to even notice the requirements of freedom for its own sake.", "\n\nFreeman says: Yes, and some of us are even on the record proving that we were against the process all along.", "\n\nNo, some of you are on the record claiming as such, not proving it. ", "Such claims aren't believable, given past performance.", "\n\nSynova says: Do you *really* think this is the same speech? ", "If it's the same speech why not release it when the decision was made to release it instead of days later?", "\n\nI know enough about political logistics to know that oftentimes, speeches aren't finalized until shortly before the time they are given. ", "Also, I have no reason to believe that anything other than a bland speech to schoolchildren was written, given the audience. ", "But, hey, weren't you the one saying that you could expect Obama's speech to be 100% composed of socialist platitudes? ", "Please, show us examples to prove this point, now that you have the text of the speech available.", "\n\nI believe I said that there was a 100% chance of the inclusion of socialist platitudes but I have come to realize that socialism does not exist. ", "Nor Marxism. ", "Nor communism.", "\n\nBecause I'd call anything urging a communal responsibility, doing good works for your fellow man, save the earth and polar bears, and volunteer to work for nothing because it's a requirement you can't get out of... to fall somewhere in the white-space between those categories.", "\n\nBut I've come to realize that because \"socialism\" and \"communism\" are bad things, that nothing anyone thinks is good could possibly be either.", "\n\nA person or organization can make a statement that the DOE should not be spending tax dollars developing lesson plans in support of the president's political agenda, or expressing shock that the lesson plans include instructions to teachers to encourage the children to think of ways to help the president, or explain that a nationwide broadcast to a captive audience of children is way too much like Big Brother for comfort...\n\n... and it all gets reduced to \"you just don't like this president and are making up those reasons, you don't really think that.\"", "\n\nsomefeller: Now that the speech has been released, and it's obvious that the speech will be the non-partisan...\n\nWhen I first read the speech all I could tweet about was how political it was. ", "Obama spends about 10 percent of it on personal propaganda, telling everyone how great and admirable he is (plus his wife).", "\n\nHis talk of specific children (by name and with city) is something pulled straight from a political playbook.", "\n\nI did like this bit though:\n\n\"I know that sometimes, you get the sense from TV that you can be rich and successful without any hard work\"\n\nThanks for the compliment. ", "On the other hand, if you were making a reference to the song \"More Than Words\", that was a song from the craptastic 80s band called Extreme (whose lead singer went on to nearly kill Van Halen as a respectable rock band), not Mr. Big.", "\n\nWord Verification: angsta - the term for conservatives who are always whining and screaming about Obama, socialism and fluoridated water." ]

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[ "The purpose of this proposal is to develop statistical methodology for analyzing the process of medical diagnosis. ", "We conceive of the process as involving three major stages. ", "The first stage occurs when a patient presents with a clinical problem, manifested by signs, symptoms or other indications. ", "We are required to determine, on the basis of this clinical information, a suspected diagnosis, selected from many potential diagnoses. ", "The classical statistical method for performing this determination is usually referred to as discriminant analysis. ", "The second stage involves assessing the properties of an available diagnostic test or tests. ", "Measures frequently used for such an assessment are the sensitivity, specificity, ROC curve, and predictive values. ", "The third stage involves determining whether it is cost-effective to perform the diagnostic test. (", "The diagnostic test under consideration may be one of several alternatives). ", "This determination should ideally involve a decision analysis, in which the utilities of the possible test outcomes and subsequent management strategies are assesed. ", "We plan to examine available statistical methods for each of these three stages of analysis, identify problems with the available methodology, and develop new methodology where appropriate." ]

{ "pile_set_name": "NIH ExPorter" }

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[ "Not Applicable\nThis invention relates generally to the field of automotive wheel finishing, and more particularly to a machine, and fixture for surfacing, deburring, radiusing, descaling, polishing, abrading, or otherwise preparing automotive wheels for the application of many types of coating, plating, painting, and also to create a variety of final polishes or xe2x80x9cfinishesxe2x80x9d for automotive wheels.", "\nMachines for finishing small work pieces in a rotational barrel configuration are well known; however, a machine with the necessary fixturing and process for finishing automotive wheels through accelerated positive gravity induced burnishing is completely unknown in the automotive wheel manufacturing and finishing industries. ", "In fact, manufacturers of automotive wheels currently use no type of a rotational barrel configuration technology to achieve the necessary pre-finishing preparation or to apply a variety of final xe2x80x9cfinishesxe2x80x9d to automotive wheels. ", "Finishing of large work pieces such as wheels requires a machine and fixturing system for holding the wheels to permit the wheels to receive high energy impacts from slurry mixtures without damaging the surface of the wheel in undesirable ways. ", "Further, there does not exist a means for reducing the heat and pressure buildup in high energy machines running at high rotational speeds and generating large G forces.", "\nFinishing small work pieces in a rotational barrel configuration is accomplished by use of slurry mixtures to create forces against the work pierces to grind down imperfections by utilizing gravitational forces to impart the force to the work piece in a desired fashion. ", "Typically, the work pieces are placed loosely in a barrel and allowed to impact each other as well as the slurry mixture. ", "Prior machines and methods for finishing small work pieces used hexagonal barrels mounted within a turret. ", "The barrels typically moved in a counterclockwise fashion from the turret in such a way as to maintain a fixed position of the barrel with respect the horizon. ", "This approach permitted the maximum impacting of the slurry mixture on the work pieces by agitating the system as the barrels rotated.", "\nThe deficiency of the prior technology is that there has existed no means or method for securing large work pieces such as automotive wheels in the proper position in a rotational barrel configuration machine to achieve an effective result. ", "Further, no large barrels existed to hold automotive wheels and perform at high rotational speeds to achieve the desired results. ", "Consequently, no machines utilizing a rotational barrel configuration have ever been developed with barrels of sufficient size to contain automotive wheels due, in part, to the lack of mechanisms for fixturing the wheels properly. ", "Another problem solved by the instant invention when utilizing the large barrel sizes required to hold automotive wheels is a means for reducing the extreme heat and consequent pressure build-up inside the barrel which would result in unavoidable leakage detrimental to the process. ", "Such means are integrated into the barrels and permit the entry of coolants to the system during rotation.", "\nA further advantage of the presently disclosed system is the quick and simple loading and unloading of cartridges that may be inserted into barrel containers from the end of the rotating turrets. ", "By end loading the cartridges through openings in the turret, insertion of wheels for finishing and removable of wheels is facilitated.", "\nAn object of the invention is to provide a viable method for machine pre-finishing and final finishing of automotive wheels.", "\nAnother object of the invention is to provide an efficient system for loading and unloading cartridges into a rotating turret from the end.", "\nAnother object of the invention is to provide a method for high force pre-finishing and finishing of automotive wheels.", "\nAnother object of the invention is to allow automotive wheels going through the pre-finishing or final finishing process to become more controlled, thus making the automotive wheel more concentric.", "\nAnother object of the invention is to allow automotive wheels going through the pre-finishing or final finishing process to be prepared or finished throughout. ", "The front, the back, the top, the bottom, the sides, inside crevasses, inside holes are radiused and polished creating a pre-finish or finish and otherwise eliminating sharp edges everywhere.", "\nAnother object of the invention is to provide a method for reduced time in pre-finishing or finishing automotive wheels.", "\nAnother object of the invention is to provide fixturing methods for automotive wheels, which make utilization of the invention and related technology possible.", "\nAnother object of the invention is to provide a system to introduce a circulating coolant into the barrel while in motion to alleviate the extreme heat and consequent pressure build-up inside the barrel, which would necessarily result from the G forces and friction generated to pre-finish or finish an object the size of an automotive wheel.", "\nAnother object of the invention is to provide a system for loading and unloading cartridges into a rotatable turret through openings in the turret to facilitate rapid re-loading of automotive wheels for finishing.", "\nIn accordance with a preferred embodiment of the invention, there is disclosed a machine for finishing automotive wheels having a rotatable turret, a plurality of containers that are journaled on the turret and capable of selective rotation independent of the turret; a plurality of removable cartridges insertable from the end into each of the containers for holding automotive wheels in the cartridges for selective reception of the media about the wheels.", "\nIn accordance with another preferred embodiment of the invention, there is disclosed a machine for finishing automotive wheels having a rotatable turret, a plurality of barrel cages that are journaled on the turret and capable of selective rotation independent of the turret; a plurality of cartridges capable of receiving media and of being stably held inside barrel cages; and a fixture in the cartridges that holds automotive wheels in the cartridges for reception of the media.", "\nOther objects and advantages of the present invention will become apparent from the following descriptions, taken in connection with the accompanying drawings, wherein, by way of illustration and example, an embodiment of the present invention is disclosed." ]

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[ "Q:\n\nHow to move bezier curve points along circle to form a symmetric curve at center\n\nFrom the image below, A is an open bezier curve with it's points positioned to represent a circle. ", "AP3 and AP1 have the same position.", "\nFrom B, How can I move the points (AP1 and AP3 along the bigger circle of radius r whiles the CP's reduce in length as CP1 and CP4 also rotate) till they form a symmetric bezier curve at the center of the bigger circle marked as the red curve?", "\n\nA:\n\nTo keep things simple & consistent, let's stick with circular arcs throughout.", "\nWe'll have our first circle with radius \\$r_1\\$, shown in red below.", "\nThen we'll use a second radius \\$r_2\\$ to define the new positions of our endpoints as the curve swings open by an angle \\$\\alpha\\$, shown on the green circle below.", "\nThen we'll draw a third circle, through our moved anchor points \\$AP_1\\$, \\$AP_3\\$ and the one we left stationary \\$AP_2\\$, shown in blue below. ", "This gives us a unique arc to follow.", "\n\nSince we already know how to trace a circular arc with a cubic Bézier curve, once we find this circle we'll be able to draw the arc along it trivially. ", "So I'll focus on finding the parameters of the circle below:\nLet's get down to placing the points. ", "For simplicity I'm going to assume that the fixed point is always at the rightmost edge of the red circle, and that the centers & radii of the circles \\$ \\vec C_1, r_1, \\vec C_2,r_2\\$ are known, along with the angle \\$ \\alpha > 0\\$ you want to open the initial curve by. (", "For \\$\\alpha = 0\\$, we just draw the original curve as in your previous question)\nNow, we know our top anchor point is at...\n$$\\vec {AP_1} = \\vec C_2 + r_2 \\cdot \\left(-\\cos \\alpha, \\sin \\alpha \\right)$$\nand our fixed anchor point is at...\n$$\\vec {AP_2} = \\vec C_1 + \\left( r_1, 0 \\right)$$ \nThen the midpoint of the line joining these is at...\n$$ \\vec M = \\frac 1 2 \\cdot \\left( \\vec {AP_1} + \\vec {AP_2} \\right)$$\nA perpendicular \\$\\vec p\\$ from this midpoint will point the way to our third center \\$\\vec C_3\\$\n$$ \\vec p = \\left( -M_y, M_x - {AP_2}_x \\right)$$\n(If \\$p_y = 0\\$ then we've opened the curve all the way to a straight line, so just draw a straight line from \\$AP_1\\$ to \\$AP_3\\$ and you're done)\nWe can scale this by a factor \\$t\\$ to reach the horizontal axis and locate our center:\n$$t = \\frac {{AP_2}_y - M_y} {p_y}$$\n$$\\vec C_3 = \\vec M + t \\cdot \\vec p$$\n$$r_3 = {AP_2}_x - {C_3}_x$$\nAnd now we can find our angle \\$\\theta\\$ with:\n$$\\theta = atan2(\\vec {AP_1} - \\vec C_3)$$\n(Just note that in many APIs, the first argument of atan2 is y not x, so be sure you put the components in the right order)\nNow we have a center (\\$\\vec C_3\\$), a radius (\\$r_3\\$), a start angle (0), and an end angle (\\$\\theta\\$), so we can draw a cubic Bézier curve along this circular arc using the technique described in my earlier answer.", "\nFor the lower half, just flip the y coordinates along the horizontal.", "\n\nHere's an animation of this method in action:\n\nWith a little attention to our start points, we can even make this work starting from a less-than-full circle:\n\nHere's the code I used:\n// Buffer for our final spline's anchor & control points.", "\nVector2[] _bezierPoints = new Vector2[7];\n\n// How much of the inner circle should we start with?", "\n[Range(0,180)]\npublic float circleCoverageDegrees= 180f;\n\n// Size & center of our inner circle (red).", "\npublic float firstRadius = 1.0f;\npublic Vector2 firstCenter;\n\n// Size & center of our second circle (green).", "\npublic float secondRadius = 2.0f;\nVector2 _secondCenter; // Computed from radius & coverage.", "\n\n// How far should we swing the anchor points out around the green circle?", "\n[Range(0, 180)]\npublic float swingOutDegrees = 0f;\n\n// Size & center of our third circle (blue).", "\nVector2 _thirdCenter;\nfloat _thirdRadius;\n\n// Used to mark the line from the second circle's center\n// to our inner anchor points before we've swung them outward.", "\nVector2 _secondToInnerStart;\n\nvoid OnValidate()\n{\n if (secondRadius < firstRadius)\n secondRadius = firstRadius;\n\n // Place the anchor points of the original circle.", "\n // (For now, I assume its center is (0, 0), and add it as an offset later)\n Vector2 innerArcStart = PointOnCircle(firstRadius, circleCoverageDegrees);\n Vector2 fixedAnchor = PointOnCircle(firstRadius, 0f);\n\n // Place the second center so the green circle passes through the endpoints.", "\n float horizontalDeviation = Mathf.", "Sqrt(secondRadius * secondRadius - innerArcStart.y * innerArcStart.y);\n _secondCenter = new Vector2(innerArcStart.x + horizontalDeviation, 0f);\n\n _secondToInnerStart = innerArcStart - _secondCenter;\n\n float startDegrees = Mathf.", "Approximately(_secondToInnerStart.x, 0) ? ", "90f \n : Mathf.", "Rad2Deg * Mathf.", "Atan(-_secondToInnerStart.y / _secondToInnerStart.x);\n\n // Swing out our anchor points along the green circle.", "\n Vector2 finalArcStart = _secondCenter + PointOnCircle(secondRadius, 180 - startDegrees - swingOutDegrees); \n\n // Find the center of the blue circle joining these anchors.", "\n Vector2 midpoint = (finalArcStart + fixedAnchor) / 2f;\n Vector2 perpendicular = new Vector2(-midpoint.y, midpoint.x - fixedAnchor.x);\n\n // If they're in a vertical line, abort and just draw a straight line.", "\n if(Mathf.", "Approximately(perpendicular.y, 0f)) {\n _thirdRadius = float.", "PositiveInfinity;\n\n _bezierPoints[0] = firstCenter + finalArcStart;\n _bezierPoints[3] = firstCenter + fixedAnchor;\n _bezierPoints[6] = 2 * firstCenter - finalArcStart;\n\n _bezierPoints[1] = Vector2.Lerp(_bezierPoints[0], _bezierPoints[3], 1f / 3f);\n _bezierPoints[2] = Vector2.Lerp(_bezierPoints[0], _bezierPoints[3], 2f / 3f);\n _bezierPoints[4] = Vector2.Lerp(_bezierPoints[3], _bezierPoints[6], 1f / 3f);\n _bezierPoints[5] = Vector2.Lerp(_bezierPoints[3], _bezierPoints[6], 2f / 3f);\n return;\n }\n\n // Phew, we have a non-infinite circle! ", "Place its center & radius.", "\n float t = -midpoint.y / perpendicular.y;\n\n _thirdCenter = new Vector2(midpoint.x + t * perpendicular.x, 0f);\n _thirdRadius = Mathf.", "Abs(_thirdCenter.x - fixedAnchor.x);\n\n // Find the angle of the endpoints around this blue circle.", "\n Vector2 thirdToFinalStart = finalArcStart - _thirdCenter;\n float angle = Mathf.", "Rad2Deg * Mathf.", "Atan2(thirdToFinalStart.y, thirdToFinalStart.x);\n\n // Handle reversing concavity correctly.", "\n float pivot = _thirdCenter.x < fixedAnchor.x ? ", "0 : 180;\n\n // Populate our Bezier curve buffers using code from previous answer.", "\n BezierCircle(_thirdCenter, _thirdRadius, angle, pivot, _bezierPoints, 0);\n BezierCircle(_thirdCenter, _thirdRadius, pivot, 2 * pivot - angle, _bezierPoints, 3);\n}\n\n// Convenience method for plotting a point in polar coordinates.", "\nstatic Vector2 PointOnCircle( float radius, float angleDegrees) {\n float angleRadians = angleDegrees * Mathf.", "Deg2Rad;\n return radius * new Vector2(Mathf.", "Cos(angleRadians), Mathf.", "Sin(angleRadians));\n}\n\n" ]

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[ "A Critical Review of Properties and Analytical Methods for the Determination of Oxytetracyline in Biological and Pharmaceutical Matrices.", "\nAntibiotics have an unquestionable importance in the treatment of many infections. ", "Oxytetracycline is an antibiotic belonging to the class of tetracyclines, available for use in human and veterinary medicine. ", "Development of analytical methods that prove the quality and efficacy of these drugs is fundamentally important to the pharmaceutical industry. ", "In this context, the research presents an overview of the analytical profile of oxytetracycline, describing its chemical and pharmacological properties, and analytical methods for quantification of this drug in biological samples and pharmaceutical products. ", "Oxytetracycline can be analyzed in these matrices by many types of methodologies. ", "However, high-performance liquid chromatography is the most widely used, being recommended by official compendia. ", "This kind of study can be useful to support the development of new efficient and sustainable analytical methods that may be utilized in the quality control routine of oxytetracycline in pharmaceutical products and pharmacokinetic monitoring in biological samples." ]

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[ "McDuffie County, Georgia\n\nMcDuffie County is a county located in the U.S. state of Georgia. ", "As of the 2010 census, the population was 21,875. ", "The county seat is Thomson. ", "The county was created on October 18, 1870 and named after the South Carolina governor and senator George McDuffie.", "\n\nMcDuffie County is part of the Augusta-Richmond County, GA-SC Metropolitan Statistical Area.", "\n\nHistory\nMost communities located in the county were founded before the county was created. ", "Some have faded into obscurity. ", "The Historic Wrightsborough Foundation preserves the memory of the early settlement of Wrightborough, which was occupied 1768 to 1920.", "\n\nGeography\nAccording to the U.S. Census Bureau, the county has a total area of , of which is land and (3.4%) is water.", "\n\nMost of the southern half of McDuffie County, south of Thomson, is located in the Brier Creek sub-basin of the Savannah River basin, except for a slice of the eastern portion of the county, north of Dearing and along a north–south line running through Boneville, which is located in the Middle Savannah River sub-basin of the Savannah River basin. ", "The northern half of McDuffie County, north of Thomson, is located in the Little River sub-basin of the same Savannah River basin.", "\n\nMajor highways\n\n Interstate 20\n U.S. Route 78\n U.S. Route 221\n U.S. Route 278\n State Route 10\n State Route 12\n State Route 17\n State Route 43\n State Route 47\n State Route 150\n State Route 223\n State Route 402 (unsigned designation for I-20)\n\nAdjacent counties\nLincoln County (northeast)\nColumbia County (east)\nRichmond County (southeast)\nJefferson County (south)\nWarren County (west)\nWilkes County (northwest)\n\nDemographics\n\n2000 census\nAs of the census of 2000, there were 21,231 people, 7,970 households, and 5,857 families living in the county. ", " The population density was 32/km² (82/mi²). ", " There were 8,916 housing units at an average density of 13/km² (34/mi²). ", " The racial makeup of the county was 60.78% White, 37.52% Black or African American, 0.89% Native American, 0.2% Asian, 0.03% Pacific Islander, 0.32% from other races, and 0.76% from two or more races. ", " 1.34% of the population were Hispanic or Latino of any race.", "\n\nThere were 7,970 households out of which 36.30% had children under the age of 18 living with them, 49.70% were married couples living together, 19.20% had a female householder with no husband present, and 26.50% were non-families. ", "23.20% of all households were made up of individuals and 9.40% had someone living alone who was 65 years of age or older. ", " The average household size was 2.62 and the average family size was 3.08.", "\n\nIn the county, the population was spread out with 27.90% under the age of 18, 8.60% from 18 to 24, 28.40% from 25 to 44, 23.20% from 45 to 64, and 11.90% who were 65 years of age or older. ", " The median age was 35 years. ", "For every 100 females, there were 89.40 males. ", " For every 100 females age 18 and over, there were 84.50 males.", "\n\nThe median income for a household in the county was $31,920, and the median income for a family was $38,235. ", "Males had a median income of $30,147 versus $20,499 for females. ", "The per capita income for the county was $18,005. ", " About 14.10% of families and 18.40% of the population were below the poverty line, including 26.00% of those under age 18 and 20.00% of those age 65 or over.", "\n\n2010 census\nAs of the 2010 United States Census, there were 21,875 people, 8,289 households, and 5,964 families living in the county. ", "The population density was . ", "There were 9,319 housing units at an average density of . ", "The racial makeup of the county was 57.2% white, 39.8% black or African American, 0.3% Asian, 0.3% American Indian, 0.1% Pacific islander, 0.9% from other races, and 1.4% from two or more races. ", "Those of Hispanic or Latino origin made up 2.2% of the population. ", "In terms of ancestry, 18.4% were American, 8.3% were English, 6.0% were Irish, and 5.4% were German.", "\n\nOf the 8,289 households, 36.7% had children under the age of 18 living with them, 45.0% were married couples living together, 21.4% had a female householder with no husband present, 28.0% were non-families, and 24.2% of all households were made up of individuals. ", "The average household size was 2.60 and the average family size was 3.07. ", "The median age was 38.4 years.", "\n\nThe median income for a household in the county was $35,414 and the median income for a family was $42,472. ", "Males had a median income of $34,300 versus $22,710 for females. ", "The per capita income for the county was $17,261. ", "About 16.0% of families and 19.5% of the population were below the poverty line, including 27.2% of those under age 18 and 20.1% of those age 65 or over.", "\n\nEducation\n\nCommunities\n\nCity\nThomson\n\nTown\nDearing\n\nUnincorporated communities\nAutney\nBoneville\nCobbham\n\nPolitics\nTypical of many counties in Georgia and the Solid South, McDuffie County almost exclusively backed candidates of the Democratic Party in presidential elections by wide margins prior to 1964. ", "The exceptions to this were 1928, when Herbert Hoover won the county by 9 points, and 1960, where John F. Kennedy only won by 40 votes, both thanks to anti-Catholic sentiment. ", "The county swung hard to support Barry Goldwater in 1964 thanks to opposition towards the Civil Rights Act, and was won by George Wallace in 1968 for similar reasons. ", "Since then, the only times the county has failed to back a Republican candidate for president since then have been in 1976 and 1980, when Georgian Jimmy Carter was on the ticket. ", "However, its sizeable African-American population has kept the Republican margins of victory lower than in many other rural counties in the state.", "\n\nSee also\n\nCentral Savannah River Area\nNational Register of Historic Places listings in McDuffie County, Georgia\n\nReferences\n\nExternal links\n Official County Website\n\nCategory:Georgia (U.S. state) counties\n \nCategory:1870 establishments in Georgia (U.S. state)\nCategory:Augusta metropolitan area\nCategory:Populated places established in 1870" ]

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[ "Fiction\n\nThe Storms by Sarah Thankam Mathews\n\nFuck All Gall by Abeer Hoque\n\nBarri Ammi by Palvashay Sethi\n\nAlligators by Tara Isabel Zambrano\n\nSecond Midnight by Devi S. Laskar\n\nEscape to Buzzkill Falls by Hasanthika Sirisena\n\nA Strange Call from the Mountain by Feroz Rather\n\nGrand Tour by Aatif Rashid\n\nThe Installation by Ahsan Butt\n\nThe Death of a Glacier by Nur Nasreen Ibrahim\n\nGas Station by Chaya Bhuvaneswar\n\n“Raid on Madras” by Aditya Desai\n\nArt\n\nRoad Trips & Bad Trips by Mariam Jajja (above & below)\n\nThe Storms & Grand Tour by Senna Ahmad\n\nFuck All Gall by Anum Awan\n\nBarri Ammi & The Death of a Glacier by Seyhr Qayum\n\nAlligators & Gas Station by Nahal Hashir\n\nSecond Midnight & The Installation by Nazish Chunara\n\nA Strange Call from the Mountain & “Raid on Madras” by Hafsa Ashfaq\n\nConversations\n\nPart I: Aditya & Sarah\n\nPart II: Nur & Abeer\n\nPart III: Sarah & Palvashay\n\nPart IV: Devi & Tara\n\nPart V: Aatif & Devi\n\nPart VI: Chaya & Hasanthika\n\nPart VII: Palvashay & Feroz\n\nPart VIII: Ahsan & Aatif\n\nPart IX: Hasanthika & Ahsan\n\nPart X: Abeer & Nur\n\nPart XI: Tara & Chaya\n\nPart XII: Feroz & Aditya\n\nPart XIII: The Artists’ Roundtable\n\nFrom the Editor\n\nOn Being Late to the Party by Kamil Ahsan" ]

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[ "One of the stock jokes of the 1950s Ealing comedies involved slightly batty people saying things that everyone else, but not they themselves, knew were entirely inconsistent with each other. ", "If events in the last couple of weeks are anything to go by, the Ealing Labour MP Rupa Huq looks set fair to revive this tradition, though this time the cause is deadly serious.", "\n\nFor some time now, pro-life, mainly Christian, protesters have kept vigil outside a Marie Stopes abortion clinic in one of the leafier parts of Ealing in west London. ", "They make clear what they think of the clinic, and in a fairly original way: handing its clients teddy bears and calling them ‘mum’ on the way in, and suggesting the spiritual fate that awaits them as they emerge. ", "The police decline to put a stop to it, on the understandable and commendable basis that the protesters – who incidentally are matched by a cohort of pro-abortion counter-demonstrators offering support to the institution and its customers – are not actually doing anything illegal.", "\n\nEaling Central and Acton MP Rupa Huq, overtly Muslim but simultaneously a pro-abortion activist, disapproves of the line taken by the protesters. ", "That is her right. ", "Much more dangerously, however, she is now taking steps to have them silenced using the heavy hand of the state. ", "A couple of weeks ago she called for Parliament to ban any demonstrations outside clinics as part of its legislative initiative against domestic violence (!) ", "Having been rightly rebuffed, she changed tack, and is now demanding that Ealing Council exercise municipal powers given to it to prevent gatherings of lager louts and drug dealers to create what she charmingly calls ‘safe spaces’ round all abortion clinics where any protests against them are barred by law.", "\n\nIt’s hard to know where to start. ", "For one thing, it’s worth noting that Dr Huq’s view of freedom of speech is clearly rather selective. ", "She wants to suppress anti-abortion demonstrations, despite having previously defended Bradford MP Naz Shah’s right to send poisonous anti-Semitic tweets and also forcefully asserted her right, as part of an alleged silent majority in Ealing, to demonstrate peacefully in favour of abortion on demand.", "\n\nFor another, rather like the petulant teenager who tells her parents to stop imposing their views on her when what she really means is that they are getting the better of the argument, Dr Huq seeks falsely to characterise the pro-life vigils and protests as a form of violence. ", "The protesters, on this argument, are somehow to be regarded as using force to prevent clients getting into the clinic or compromising their safety. ", "Quite how is not clear, though she does refer engagingly at one point to ‘weaponising rosary beads’ – an idea at which the mind boggles.", "\n\nScratch below the surface, moreover, and you find something else which is all too common in the liberal establishment. ", "This is the idea that freedom of speech is all very well, but it must stop where it causes any kind of discomfort or distress to those who don’t share your views. ", "Dr Huq herself lets the cat out of the bag when she says that her aim is to prevent abortion clients feeling ‘uncomfortable accessing services’. ", "The right to abortion, itself controversial, has now apparently morphed into a right to have an abortion with a clear conscience, protected from criticism or adverse comment.", "\n\nIt never seems to strike the worthy Dr Huq that by saying this she seems to be admitting to a profound personal unhappiness with the whole idea of free expression and argument. ", "Outside some university debating chamber, the very point of criticising the morality of what someone else is doing is to make them feel uncomfortable about it. ", "Prevent this, and you are essentially saying that you are happy to allow free speech to those who disagree with you, provided it isn’t effective. ", "Once there is a chance that your opponents may start winning the argument, then it’s open season for you to take steps forcibly to shut them up. ", "That’s what Dr Huq is trying to do with respect to Ealing Council and the Marie Stopes clinic. ", "Whether she will succeed in this remains to be seen: but one fears the omens for free speech are not good." ]

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[ "\n\n\n\nVideodrome – Riot Control – Freemasons\n\nJack the Ripper – Illuminati – JFK Assassination\n\nMark Stewart – Robert Anton Wilson\n\n\n\n‘Vague is an extremely intense, radical, funny, el cheapo, deep-biting English mag with indescribable assortment of subject matter. ", "Ugly as sin, but invaluable.’ ", "Ivan Stang Sub-Genius Foundation\n\n‘Vague has slack; Vague has Sub-Genius brag; Vague has discord and anarchy; Vague has Situationism, psychic terrorism, helter skelter urban shamanism, conspiracy, paranoia and manipulation. ", "It has captured, hi-jacked and bound the current that at times drove Oz in the 60s. ", "Vague cries out for, and defies, censorship and suppression. ", "Vague is the underground overground.’ ", "Joel Biroco Kaos\n\nVague 18/19 Control Data Manual was a conspiracy theory greatest hits featuring JFK, Jack the Ripper, Freemasons, the Illuminati, the occult roots of Nazism, Neoism, Hassan i Sabbah, Charles Manson, Bilderbergers, Trilateral Commission, Scientology, Church of the Sub-Genius, Worldwide Alienation Inc by Mark Stewart, Videodrome – the hyper-Situationist theory of Mark Downham, etc, etc.", "\n\nVideodrome Programming Phenomena The Thing In Room 101 by Mark Downham. ", "In the Videodrome no one can hear you scream. “", "You asked me once”, said O’Blivion, “what was in Room 101. ", "I told you that you knew the answer already. ", "Everyone knows it. ", "The thing that is in Room 101 is the worst thing in the world… The Videodrome.” ", "Video-spectacular life revolves around twin self-reflexive switches that activate us: Control (Authority and Obedience) and Behaviour (Production and Consumption). ", "The Videodrome is the enigma of the thing: not simply as object and commodity, but as pure object and absolute commodity. ", "The Videodrome is the point where the image is more concretised, more commodified than the commodity.", "\n\nThe Spectacle now has a new organisation of appearances – video DNA life, the hyperreal; more deadly than deadly, the vampiric carnage of virulent description; and yet it moves with seemingly purposive intelligence. ", "Bending sound as the electron gun in the cathode ray tube scans the frequencies that put your brain in the alpha wave state, the relaxed state; and this totalitarianised electro-technic Oceania dredges the oceans of your subconscious in preparation for the embedding. ", "The Spectacle is going through an evolutionary jump and is becoming more than the facility with which images can be detached and alienated from their sources and reorganised for representation in accord with initial stages of the Spectacle; where everything that was once directly experienced has already shifted in to its own representation.", "\n\nThe Spectacle has always been more than just a collection of images; and the Spectacular Videodrome is much more than just a social relation among people mediated by images, more than capital to such a degree of accumulation that it becomes an image – it is a video DNA gestalt. ", "The Videodrome is Debordment overflow; it is hyper-visibility; here even terrorism is a neurosis – the violence of a society without secrets; totally media-transparent, a spectacular gesture from the see-through silent age. ", "In the Videodrome there is nowhere to hide, there are only terminals, and we use the terminals for our alienated experiences – the spectacle of our deepest fears. ", "It is so much television that it isn’t television at all… The Videodrome is your deepest secret fears played back to you, come back to plague you – it is the destruction of the autonomous imagination…\n\nJFK Assassination ‘The motorcade passes the Texas School Book Depository and moves slowly toward the triple underpass. ", "At the 6th floor window, Lee Harvey Oswald sights carefully through the Carcano-Mannlicher: his mouth is dry, desert dry. ", "But his heart beat is normal; and no sweat stands out on his forehead. ", "This is the moment, he is thinking, the one moment transcending time and hazard, heredity and environment, the final test and proof of free will and of my right to call myself a man. ", "In this moment, now as I tighten the trigger, the tyrant dies, and with him all the lies of a cruel, mendacious epoch. ", "It is a supreme exaltation, this moment and this knowledge: and yet his mouth is dry, dust-dry, dry as death, as if his salivary glands alone rebelled against the murder which his intellect pronounced necessary and just.", "\n\n‘Now: He recalls the military formula BASS: Breath, Aim, Slack, Squeeze. ", "He breathes, he aims, he slacks, he starts to squeeze, as a dog barks suddenly – And his mouth falls open in astonishment as 3 shots ring out, obviously from the direction of the grassy knoll and triple underpass. “", "Son-of-a-bitch”, he said, softly as a prayer. ", "And he began to grin, a rictus not of omnipotence such as he had expected but of something different and unexpected and therefore better – omniscience. ", "That smirk appeared in all the photos during the next day and a half, before his own death, a sneering smile that said so clearly that none dared to read it: I know something you don’t know. ", "That grimace only faded Sunday morning when Jack Ruby pumped 2 bullets into Lee’s frail fanatic body, and its secret went with him to the grave.’ ", "Robert Shea and Robert Anton Wilson Illuminatus volume 1 page 23\n\nIlluminati/Hassan-i-Sabbah/Adam Weishaupt “Nothing is true. ", "Everything is permissible.” ", "Hassan-i-Sabbah. ‘", "Illuminati project memo 5: The nightmarish story begins in 1090AD in the middle east when Hassan-i-Sabbah founded the Ismaelian sect, or Hashishin, so called because of their use of hashish, a deadly drug derived from the hemp plant which is better known as the killer weed marijuana. ", "The cult terrorised the Muslim world until Genghis Khan’s Mongols brought law and order to the area. ", "Cornered in their mountain hideaway, the Hashishin dope fiends proved no match for the clean-living Mongol warriors, their fortress was destroyed, and their dancing girls shipped to Mongolia for rehabilitation. ", "The heads of the cult fled westward. ", "The Illuminati surfaced next in Bavaria in 1776. ", "Adam Weishaupt, a student of the occult, studied the teachings of Hassan-i-Sabbah and grew hemp in his backyard. ", "On February 2 1776 Weishaupt achieved illumination. ", "Weishaupt officially founded the Ancient Illuminated Seers of Bavaria on May 1 1776.", "\n\n‘Illuminati project memo 7: No historian knows what happened to Adam Weishaupt after he was exiled from Bavaria in 1785, and entries in Washington’s diary after that date frequently refer to the hemp crop at Mount Vernon. ", "The possibility that Adam Weishaupt killed George Washington and took his place, serving as first president for 2 terms, is now confirmed. ", "The 2 main colours of the American flag are, excluding a small patch of blue in one corner, red and white; these are the colours of the Hashishin… Memo 16: The Nazi party was founded as an appendage of the Thule society, an extremist fringe of the Illuminated lodge of Berlin. ", "This lodge in turn was made up of Rosicrucians – high freemasons – and its preoccupation was mourning the death of the feudal system. ", "Masons at this time were, like the Federalist party in post-revolutionary America, working diligently to prevent anarchy and preserve the old values by bringing about Christian socialism…’\n\nJack the Ripper Murder By Decree by Tom Vague first published in Zigzag 1985; deservedly spoofed in the Jack the Crimper flyer by God Told Me To Do It: Although the reign of terror that swept the East End of London with the Whitechapel murders is not quite a hundred years ago, Jack the Ripper has become as much a part of British folklore as Guy Fawkes, Robin Hood and King Arthur. ", "And despite his hideous acts, he’s shrouded in at least as much romance and mystery as the aforementioned. ", "Not to mention Hammer house London smog. ", "The Casebook on Jack the Ripper by Richard Whittington-Egan sets the scene thus: ‘The gas-lit, Holmesian period atmosphere, viewed from a comfortable distance, invests the entire affair and casts a romantic afterglow.’", "\n\nIn 1973 the factional BBC series, The Barlow and Watt Investigation into the Whitechapel murders was prompted by a new theory that emerged around 1970. ", "As it seemed that there was nothing left to say on the subject, a sensational article had appeared accusing Queen Victoria’s grandson, Prince Albert Victor, the Duke of Clarence of being Jack the Ripper, causing a revival of Ripper-mania. ", "The BBC put a features and drama crew on the case to get ‘the final word on Jack the Ripper’. ", "At New Scotland Yard they found the legendary closed file on the Whitechapel murders wasn’t to be opened until 1992. ", "Instead they got a tip-off from a senior Yard man to contact one Joseph Sickert. ", "He told them of a marriage between the Duke of Clarence and a commoner; the murder victims had been the witnesses and the whole affair a macabre cover up.", "\n\nStephen Knight, the author of Jack the Ripper: The Final Solution, initially approached Joseph Sickert for a local press follow-up story after the Barlow and Watt TV series. ", "His description of the old man on first sight was ‘rugged and aristocratic’. ", "Joseph Sickert described his mother as a nervous woman who had spent her childhood in workhouses and gave the impression that she was burdened with some dreadful secret; adding that she would become particularly tense and nervous when she saw a policeman. ", "According to Joseph, when he came of age, his father, the Impressionist painter Walter Sickert, told him the royal Ripper story.", "\n\nPrince Albert Victor, known as Eddy, was showing no inclination towards his royal duties and was a big disappointment to his father Prince Edward (later Edward VII). ", "His doting mother, Princess Alexandra decided that he would be better suited to artistic circles than the academic world. ", "So she asked Walter Sickert to take him under his artistic wing. ", "He introduced him to Cleveland Street, which runs parallel with Tottenham Court Road, then a thriving Bohemian community of artists, writers and revolutionaries including William Morris and Bernard Shaw. ", "There Prince Eddy met and fell in love with Annie Elizabeth Crook, an occasional model for Sickert. ", "He’s more commonly thought to have been involved in the gay Cleveland Street scandal, though that doesn’t rule him out as a Ripper suspect.", "\n\nIn 1885 Annie Crook gave birth to a baby girl, Alice Margaret. ", "Shortly after Eddy and Annie were married at a Catholic ceremony. ", "The witnesses were Walter Sickert and the Irish nanny Mary Kelly. ", "Sickert himself married that year and began to travel back and forth to Dieppe, where he painted some of his finest works. ", "In due course news of Prince Eddy’s dangerous liaison reached the Queen, who wrote to the prime minister Lord Salisbury commanding him to deal with the situation. ", "As Stephen Knight puts it, Lord Salisbury ‘could see that Eddy had been sowing not only wild oats, but the seeds of revolution.’ ", "In Ireland Victoria was known as ‘the famine queen’, there had been bombings and assassination attempts and in 1887 the ‘Bloody Sunday’ riot in Trafalgar Square.", "\n\nIn Walter Sickert’s story recalled by his son, in early 1888 a raid was staged under the cover of a street brawl in which Prince Eddy and Annie Crook were bundled into separate cabs, never to see each other again. ", "Annie was certified insane and ended up in an asylum. ", "But somehow Mary Kelly escaped from Cleveland Street with their child and hid her in the East End. ", "She got the child to Sickert, who put her in the care of poor relatives and she eventually became his ward in Dieppe. ", "Meanwhile Mary Kelly had confided in a group of Whitechapel prostitutes that she had fallen in with and a blackmail plot was hatched. ", "According to the Sickert story, this set in motion a masonic conspiracy to silence the women orchestrated by the queen’s physician Sir William Gull.", "\n\nIn the autumn of 1888 the gruesome murders were committed according to time honoured masonic ritual, with the assistance of Prince Eddy’s former coachman John Netley. ", "Mary Ann Nichols (in Buck’s Row), Annie Chapman (in Hanbury Street) and Long Liz Stride (in Berner Street) were enticed into Netley’s cab, where Gull would be waiting for them. ", "Thus explaining the short space of time in which the murders and the complicated gory finishing touches took place. ", "Sickert claimed there was a third party in the conspiracy, none other than Sir Robert Anderson, the assistant commissioner of the Metropolitan Police, who deliberately fuelled the terror and panic to confirm masonic supremacy. ", "But something went wrong and Catherine Eddowes became the 4th victim in Mitre Square, instead of the original target Mary Kelly. ", "So there was a lull in the proceedings until the day of the Lord Mayor’s show, when Mary Kelly became the final victim in Dorset Street and Jack the Ripper disappeared.", "\n\nThe best evidence of the masonic Ripper theory is the writing on the wall. ", "As re-enacted in Murder by Decree (and From Hell), a piece of Catherine Eddowes’ blood-soaked apron was found in the passageway of 108-119 Wentworth Buildings on Goulston Street off Petticoat Lane (Middlesex Street). ", "Above it on the wall was chalked: ‘The Juwes are the men that will not be blamed for nothing.’ ", "This wasn’t a miss-spelt incitement to anti-Semitism, as was originally thought, but an incriminating reference to the mythical mason murder during the construction of Solomon’s temple around which all masonic ritual is based. ", "The Metropolitan Police commissioner Sir Charles Warren, another high-ranking freemason, came to the scene to wipe away the only piece of evidence the Ripper left. ", "The passageway, opposite the Last Resort skinhead shop, is one of the few remaining Ripper sites, albeit boarded-up and about to be demolished by the looks of it.", "\n\nIn Jack the Ripper: The Final Solution, Stephen Knight dismissed the other Ripper theories; Leather Apron – the mad pork butcher, the mad Russian doctor, an escaped gorilla, Jill the Ripper, and Montague Druitt – the sexually insane doctor. ‘", "I’m not a butcher, nor a Yid, nor yet a foreign skipper, but I’m your own light-hearted friend, yours truly, Jack the Ripper.’", "\n\n\n\n\n\nTom Vague\n\n(Vague Publishing, 1987)\n\n\n\nnow out of print\n\n" ]

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[ "School districts are required to maintain a certain student to staff ratio, provide certain required courses, while remaining within budgets for their district. ", "In some districts teachers and students may move between campuses during the day for classes offered at a different campus than their home campus. ", "In some districts, there is a facility that all campuses share for certain classes. ", "Determining staffing for the courses at the shared facility and also at each individual campus can be challenging for districts as enrollment fluctuates and students' course needs and wants fluctuate as well. ", "What is needed is a system for determining staffing requirements for secondary education campuses." ]

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[ "Disclaimer: This web site is designed for general information only and does not create attorney-client relationship. ", "Persons accessing this site are encouraged to seek independent counsel for legal advice regarding their individual legal issues.", "\n\nsurname\n\nmy name is anthony sy,and i have a problem with my surname.my parents are not married,and im using my father's surname since elementary to college,but i found out that my surname in my birth certificate is my mother's,and now i am married using my father's surname,is our marriage valid?..thank you\n\nis your father still alive? ", "all he has to do is issue an authority to use surname of father at the civil registrar where your birth certificate was registered and this should sufficiently cure the defect.", "\n\nand regardless, your marriage is still valid because the name refers to you.", "\n\n_________________\n\n[i] Visit our FB Page: FOR MORE LEGAL ADVICE Warning and Disclaimer: I am not your lawyer; and you are not my client. ", "With the limitations of an Internet forum, a thorough review of your concern is not possible. ", "View my comments at YOUR OWN RISK. ", "It is best to actually retain a lawyer for your individual concerns.", "\n\ndid your father sign your birth certificate? ", "here's the thing, the law says that if you were acknowledged by him, you can use the surname of your father. ", "however, the implementing rules require the issuance of the authority to use surname of father so that the birth certificate will be stamped of such fact. ", "of course this is impossible because your father has passed away.", "\n\nnevertheless, this matter does not affect the validity of your marriage, but there will be complications later on with the names of your children and other situations where this issue will crop up.", "\n\n_________________\n\n[i] Visit our FB Page: FOR MORE LEGAL ADVICE Warning and Disclaimer: I am not your lawyer; and you are not my client. ", "With the limitations of an Internet forum, a thorough review of your concern is not possible. ", "View my comments at YOUR OWN RISK. ", "It is best to actually retain a lawyer for your individual concerns." ]

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[ "Histone modification mapping in human brain reveals aberrant expression of histone H3 lysine 79 dimethylation in neural tube defects.", "\nNeural tube defects (NTDs) are severe, common birth defects that result from failure of neural tube closure, but their pathological mechanisms are not yet fully understood. ", "Histone modifications have an important role in gene regulation during fetal development. ", "We therefore hypothesized that the human NTDs may be partly caused by an imbalance in metabolism, perhaps caused by nutritional deficiencies, that leads to aberrant histone modifications. ", "Here, we report a screen of fetal brain histone modifications using 2D nano-LC strong cation exchange reverse phase (SCX/RP) MS/MS and the identification of 61 unique post-translational modification sites on histones H1, H2a, H2b, H3, and H4. ", "Of these, 38 sites are novel (not already found in the Uniprot database). ", "Furthermore, we compared the histone modification patterns between normal brains and NTD brains special of which maternal folate levels were lower than of normal control. ", "The results showed that histone H3 lysine 79 dimethylation (H3K79me2) and a novel identified site, H2bK5 monomethylation (H2bK5me1), were completely absent in individuals with NTDs. ", "Follow-up Western blotting validated the decreased H3K79me2 expression in brains with NTDs, but the amplified samples experiments displayed that decreased H3K79me2 expression was not suitable for all samples with NTDs. ", "Furthermore, folate-free treated mouse embryonic stem cells induced the decreased H3K79me2 level. ", "Subsequently, our ChIP results in normal fetal brain tissues showed that H3K79me2 binds to SUFU, RARA and ITGA3 which induce NTDs phenotype after knockout in mice, and in NTDs brain tissues the bindings of H3K79me2 to these three genes were significantly altered. ", "Taken together, our study indicated that low folate treatment might attenuate H3K79 dimethylation, further affect its regulate activation on target genes, some of which are NTDs-resulting associated, lastly interrupt early embryo developing. ", "Our study increases the understanding of normal fetal brain histone modifications and provides a platform for investigating histone modifications in neural disease and also has an insight into a potential role of aberrant histone modification in etiology of NTDs." ]

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[ "In 2009, I started to receive spam emails from hitherto-unknown publishers inviting me to submit articles that would then be published after passing peer review and upon receiving a payment from me.", "\n\nMy first reaction was to be appalled; I loathed the idea of having to pay for publication. ", "I also noticed that the websites of the publishers sending the email invitations looked unprofessional. ", "They contained numerous grammatical and spelling errors. ", "They frequently had the unidiomatic phrase \"Call for paper\" in a large font prominently displayed on their webpages\n\nAs an academic librarian, I was intrigued by these new publishers, many of which were based in Asia and Africa. ", "I was also interested in the economic model behind them, the author-pays model, now called gold open access. ", "In the gold OA model, the author is charged a fee when a scientific paper is accepted for publication. ", "One advantage of this model is that the journals are open-access -- everyone with a computer and an internet connection can freely access the content, including those in developing countries where access to current research is desperately needed. ", "Another advantage is the open access citation effect (OACE), in which articles published in openaccess journals receive more citations than papers published in journals that are behind a paywall ([@bib0010]).", "\n\nThe disadvantage, I soon discovered, is that the model has a fatal flaw. ", "The gold open access model is beset by a significant conflict of interest -- the more papers a publisher accepts for publication, the more money it earns, a perfect recipe for corruption. ", "The gold open-access publication model quickly spread, and in the years since 2009, hundreds of publishers using the author-pays model have appeared, some legitimate, and some corrupt.", "\n\nBack in 2009 I began to print out the spam emails I received, and I also printed out copies of the websites of the publishers sending me spam manuscript submission invitations. ", "Later, in 2010, I coined the term \"predatory publisher\" and published my first list, which contained fewer than 20 publishers. ", "The list, published on a former blog of mine, was largely ignored.", "\n\nIn 2011, I defined predatory publishers as those that unprofessionally abuse the author-pays publishing model for their own profit. ", "Throughout 2011 I continued to collect information about predatory publishers, hoping to publish a second list later in the year.", "\n\nThen I published my second list in December 2011, and it garnered much attention. ", "In early 2012, I moved my blog to a WordPress platform and gave it a new name, *Scholarly Open Access*, found at [http://scholarlyoa.com](http://scholarlyoa.com/){#intr0005}. ", "The blog contains two frequently-updated lists, one of questionable publishers and one of questionable, standalone journals.", "\n\nWith contributions and suggestions from readers, I developed a set of criteria for determining which publishers and journals belong on the lists. ", "In addition, I use the main section of the blog to share critical analysis of scholarly open-access publishing in general. ", "The many emails I receive from scholars around the world alert me to possible new additions. ", "Also, in early 2013, the blog added an appeals process. ", "A review board of four members reviews appeal requests and advises me whether to retain a publisher or to remove it. ", "Since early 2012, there has been an amazing surge of new publishers and journals, as the barrier to start up operations as an openaccess publisher is low. ", "All that one needs is a website and some unique journal titles.", "\n\nPredatory publishers are bad for science and bad for science communication for several reasons. ", "First, science is cumulative -- contemporary research builds on research recorded as part of the scholarly record. ", "Because many predatory publishers do a fake or minimal peer review, it is possible for bogus research to be published in these journals, masquerading as real science. ", "This work can then get cited in legitimate journals, dirtying future science. ", "In my blog, I have documented a case of fake peer review ([@bib0005] [@bib0005]). ", "Documenting the unethical practices of predatory publishers is difficult because most are not transparent in their operations.", "\n\nFurther, because of the dishonest peer review and the lack of proper vetting by predatory publishers, these counterfeit journals contain many instances of author misconduct. ", "This misconduct can include plagiarism and self-plagiarism, and it can extend to more serious misconduct including data and image manipulation. ", "Indeed, many predatory journals are veritable reservoirs of author misconduct.", "\n\nBecause predatory publishers earn their money through author fees, they prioritize their efforts to meet the authors' needs over the readers' needs. ", "For instance, let us say the average researcher publishes one article per year but reads several dozen. ", "Thus, we are more often consumers of research than we are producers of it. ", "Predatory publishers care much more about us as authors than as readers. ", "They pay insufficient attention to value-added features that benefit readers -- such as automated reference linking -- preferring instead to focus on authors' needs, such as a super-fast review process, so it is easy for potential authors to be lured into their traps. ", "This change in focus brought on by the gold open-access model is hurting all consumers of research and may threaten the future of high quality scholarly communication.", "\n\nSociety places great value on scientific research. ", "Scholarly articles reporting novel findings frequently receive press coverage. ", "Legal cases sometimes hinge on science as reported in the scientific literature. ", "Various areas of public policy also rely on findings generated from peer-reviewed research. ", "Perhaps most importantly, public health depends on honest, peer-reviewed medical research and the publishing of successful laboratory experiments that eventually get translated into clinical practice. ", "Thus competent medical practice is one of the societal needs predatory publishers most threaten. ", "Because of predatory publishers, it is possible that corrupt science might make its way into the scholarly record and eventually into practice, negatively affecting the public health.", "\n\nIn this context, doctors, as consumers of research, have a difficult task. ", "They need to avoid corrupt science by avoiding publishers whose articles have not received an honest peer review. ", "The problem is worsened by the fact that predatory publishers are most active in the bio-medical sciences, because that is where the grant money is. ", "The grant money in bio-medical research now generally funds the article processing charges (APCs) that are billed to researchers upon acceptance of their manuscripts.", "\n\nSo, more than any other group of consumers of research, doctors and health sciences researchers have the greatest need to acquire the skill I call scholarly publishing literacy. ", "This skill includes the ability to recognize and avoid publishing scams. ", "There are some simple steps that we all should take to avoid being taken in by predatory publishers and their scams.", "\n\nThe first step is to simply be aware that the scams exist, and that the scammers are very good at what they do. ", "They will communicate with you, generally using email. ", "As a general rule, all scholars should be wary of any publishing offer they receive through email.", "\n\nSome publishers have taken their spam emails to the next level, using a very effective and novel strategy. ", "They send personalized spam emails to researchers, praising an earlier work in another publication, and inviting the researcher to submit a new, similar work to the predatory publisher. ", "They frequently promise a quick review. ", "They may supply false information, claiming they have an impact factor when they really do not.", "\n\nMoreover, in their spam emails, some of the publishers fail to mention that they are a gold open-access journal that charges an article processing fee. ", "Unfortunately, many are unfamiliar with article processing fees or assume the publisher does not charge them. ", "Later, they are shocked to receive an invoice, often for over £1,000.", "\n\nSome publishers will invite you to join their editorial boards. ", "While editorial board membership on a legitimate journal offers academic credit, the chance to read new research before it is published, and the opportunity to learn about the scholarly publishing process, service on a predatory publisher\\'s editorial board can be a negative experience. ", "Many have found it difficult to get their names removed once they decide to resign from the editorial board; the publisher wants to exploit their names and affiliations to attract more articles.", "\n\nAlso be aware of invitations to guest-edit special issues of journals. ", "Typically, one of the guest-editor\\'s roles is to invite and secure the manuscripts for a special issue. ", "In the context of author-pays journals, the guest editor essentially becomes an agent for the publisher, attracting article processing payments from among his colleagues and collaborators.", "\n\nPredatory publishers frequently hide or misrepresent their true headquarters locations. ", "Many purport to be based in Anglophone countries but really hail from Asia or Africa. ", "Predatory journal titles are also often misrepresentative. ", "For example, many Asian publishers use titles that begin with \"*British Journal of* ...\" or \"*American Journal of ...*\". ", "I think there are more British journals based in Pakistan than there are in the U.K. itself.", "\n\nMedical publishing in particular and scholarly publishing in general are caught between the past and the future. ", "Scholarly communication is undergoing great changes, with some exploiting the system\\'s weaknesses. ", "As producers and consumers of research, those in the health professions need to be aware of the corrupt practices in scholarly publishing and avoid them. ", "There are still many excellent venues for sharing and reading high-quality, peer-reviewed research, and all scholars should engage with these high-quality venues and resist the temptation to conduct business with predatory publishers and journals.", "\n\nAddendum: Some warning signs of questionable publishers:•The publisher does not state its headquarters location or misrepresents its true location•The publisher sends spam email solicitations for article submissions, editorial board memberships, or special issue editorships•The publisher\\'s website contains significant typographical and grammatical errors or otherwise looks unprofessional•The publisher\\'s journal portfolio is large, with over 100 titles, many of them new and or with little content • Papers in the publisher\\'s journals are poorly copyedited•The publisher\\'s journals have a broad scope to attract more papers (e.g. *Journal of Medicine*)•The publisher\\'s email addresses are from free providers such as [gmail.com](http://gmail.com){#ir0020}, [yahoo.com](http://yahoo.com){#ir0025}, etc.", "\n\nEthical approval {#sec0005}\n================\n\nNone required.", "\n\nConflict of interest {#sec0010}\n====================\n\nNo conflicts of interest have been declared by the author.", "\n\nAuthors contribution {#sec0015}\n====================\n\nSingle author manuscript.", "\n\nFunding {#sec0020}\n=======\n\nNo funding source declared by author.", "\n\n**Provenance and Peer Review**\n\nPeer-reviewed.", "\n" ]

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[ "Euclides da Cunha, Bahia\n\nEuclides da Cunha is a municipality and town in the state of Bahia in the North-East region of Brazil.", "\n\nHistory\nThe Masakara language and Kaimbé language, now extinct, were once spoken in the municipality.", "\n\nDistricts\nMassacará (created on December 30, 1953)\nAribicé (created on November 5, 1985)\nCaimbé (created on November 5, 1985)\nRuilândia\n\nReferences\n\nCategory:Municipalities in Bahia" ]

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[ "Q:\n\nHow to write one D of a Multi-D array in one statement, in VBA?", "\n\nHow can i write an entire dimension of a multidimensional array, in a single statement?", "\nEdit 2:\nClarification:\nSimply want to update one slice (vertical or horizontal) of a VBA array, without looping/processing the entire array. ", "\n\nI'm assuming we need to convert a 2D to 1D, or 1D to 2D, array. ", "Not sure that's necessary.", "\nMy example uses a worksheet range as a source, but don't be distracted by that. ", "I'm not trying to update the worksheet-- trying to update an array. ", "The solution i seek should not require worksheet read/write. ", "\n\nEdit 1: I've got a 2D array in VBA. ", "It contains cell data pulled in from a sheet:\ndim blockData\nblockData = [a1:d10]\n\nNow, i want to copy a different cell range into that array, overwriting just one row:\ndim rowData\n' just one row of data, but same width as 2D blockData\nrowData = [a20:d20]\n\n' load into array, overwriting row 3 with this new data. ", "\n' This is the one-liner i seek:\nblockData(3,) = rowData\n\nSo, how can i write a whole 1D array to one D of a 2D array in a single statement, without looping?", "\nSome ideas:\n\nI can get a single column from the array using the INDEX trick. ", "Maybe that can be exploited somehow:\ncolArray = WorksheetFunction.", "Index(rangeArray, 0, 1)\ncolArray (1,2)=\"New cell value\"\nUse Transpose(colArray), but that has not helped so far.", "\nUse Redim Preserve to somehow combine the arrays, but not sure how\nthat can help.", "\nUse VarPtr to write my changes directory to the original array, but\nnot sure that can be done without looping.", "\nIt's easy to copy an entire array to another variable in one statement. ", "Maybe that can be exploited somehow:\nDim a1, a2\na1=array(1,2,3)\na2=a1\n\nthx\n\nA:\n\n-- if it's a meta-array (array of arrays), then a single row can be updated in a single statement:\nArrayOfArrays(12) = NewRowArray\n-- if it's a 2D array, a single column can be updated with CopyMemory. ", "Not for the faint-of-heart, and you can crash if you do it wrong (don't forget the cleanup part). ", "I've not work out the details, but some clues:\nhttps://stackoverflow.com/a/24843721/209942\n\n" ]

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[ "As a part of the ESPN+ platform, USL’s games will stand alongside top international properties, such as the English Football League, the UEFA Nations League and Major League Soccer. ", "The move to ESPN+ delivers the thrill of the USL to a broader audience across the U.S. while providing our fans with access to a large assortment professional sports that include Major League Baseball, the National Hockey League and more for a small monthly fee.", "\n\nWe want to deliver the very best viewing experience for our fans every weekend. ", "Among the many benefits to ESPN+ like convenience and accessibility is the quality of broadcast – supporting HD broadcasts for the first time, which is a result of the league’s significant investments in USL Productions.", "\n\nFans will still be able to follow their home team through local broadcast partnerships as part of the USL Television Network. ", "Also, more matches than ever before will be available on ESPNU and ESPN3 through the USL Game of the Week package.", "\n\nThis is a tremendous step forward for the USL as it continues to deliver the thrill of professional soccer to more fans and more markets across the U.S." ]

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[ "lkmjr\n\nHonestly, Heroman is a far better series than it has any right to be. ", "It's a flood of tropes from start to finish,\ncombining American superheroes with Japanese giant robots and throwing in a good-old-fashioned alien invasion just for\nkicks. ", "Heroman really doesn't offer anything new to the proverbial table, but it captures the spirit of classic Saturday\nmorning cartoons in all the right ways, mixing together and slightly modernizing old ideas and formulas to come out with\nsomething that feels fresh but still familiar.", "\n\nThis is quite possibly the most American anime I've ever seen. ", "It takes place in America, features a red white and blue\nrobot, and the one Japanese guy (judging by his name, Dr. Minami) is a villain." ]

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[ "The role of pharmacokinetics in anaesthesia: application to intravenous infusions.", "\nPharmacokinetic concepts describe the relationship between drug dose and resulting plasma concentration. ", "A drug's pharmacokinetic profile can be described by distribution and elimination half-lives, initial volume of distribution, steady-state distribution volume, and metabolic and distributional clearance. ", "After initiating a fixed rate of drug infusion, four to five terminal elimination half-lives are required to reach a steady state of constant plasma concentration. ", "If a loading dose is given, a steady state can be achieved more rapidly. ", "The most rapid method of achieving a constant plasma concentration involves using a variable rate of drug infusion that adjusts for the metabolic clearance and distribution of the drug. ", "Computer-driven infusion pumps can be used to rapidly achieve, then maintain, constant plasma concentrations of a drug." ]

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[ "[xquery-talk] Sparksoniq 0.9.1 Spruce: first alpha release\n\nDear all,\nI am happy to announce the first alpha release of Sparksoniq: 0.9.1 Spruce, under an Apache 2.0 license.", "\nYou can try it out with its shell and its documentation on\nhttp://sparksoniq.org\nIn a nutshell, this is a JSONiq engine [see below what it has to do with XQuery and XML] that runs seamlessly on top of Spark. ", "This engine was developed at ETH Zurich in collaboration with Stefan Irimescu, who wrote his Master's thesis with Gustavo Alonso and me last year and did an amazing job.", "\nThe core idea is that FLWOR expressions (identical to XQuery’s) very naturally map to Spark transformations, which allows a declarative and functional encapsulation, hiding Spark, Java and Scala from the user. ", "This is consistent with Edgar Codd’s data independence requirement. ", "This is also to put in context with several other ongoing works on the XML side such as Apache VXQuery (on Hyrack), PAXQuery (on Flink), etc.", "\nKeep it mind that this is an early version with not yet the full language, and we will do best effort to address all the bugs that will certainly be found, while keeping a specific focus on querying large-scale JSON datasets. ", "We look forward to constructive comments, bug reports, feature wish lists, missing aspects in the documentation, etc.", "\nWith many thanks and kind regards,\nGhislain\nI am adding a small note on JSONiq to give some context:\nJSONiq, which some of you already know, is XQuery 3.0’s little brother and a cousin of XQuery 3.1. ", "JSONiq’s DNA is 95% XQuery and it has all the expression machinery of XQuery, but adapted to specifically query JSON documents in a document-store-like setting, so as to be appealing to those in the JSON community who feel a bit uneasy about angle brackets, QNames, URIs and processing instructions.", "\nIt was designed by a few working group members as a proposal during the discussions on how to integrate objects and arrays into XQuery. ", "It is still alive and used, because its use case, querying JSON data natively, is different and complementary to that of XQuery 3.1, which focuses more on the data structure aspects of objects and arrays. ", "In particular, JSON is a subset of JSONiq, the data model fully mirrors JSON, navigation uses the dots JavaScript users are familiar with, etc. ", "the difference is documented more in details here [1].", "\n[1] https://stackoverflow.com/questions/44919443/what-are-the-differences-between-jsoniq-and-xquery-3-1" ]

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[ "The analysis of articular cartilage after thermal exposure: \"Is red really dead?\".", "\nPartial-thickness articular cartilage (PARC) lesions have no propensity to heal. ", "Surgical techniques have focused on halting their progression. ", "Thermal chondroplasty procedures have become controversial with regard to the viability of the remaining cartilage. ", "This controversy has expanded to the way that articular cartilage is evaluated after treatment. ", "In this article, evaluation of articular cartilage viability is reviewed." ]

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[ "РБК выяснил, как государственный «Роснефтегаз» смог получить убыток от приватизации «Роснефти». ", "Этот убыток дал холдингу возможность не платить дивиденды в 2017 году, на которые рассчитывал Минфин\n\nФото: Андрей Рудаков / Bloomberg\n\nХолдинг «Роснефтегаз», который от имени государства держит на своем балансе акции «Роснефти» и «Газпрома» рыночной стоимостью более 2 трлн руб. ", "и не занимается операционной деятельностью, перестал публиковать отчетность с 2015 года. ", "Но РБК получил через ГМЦ Росстата и проанализировал бухгалтерскую отчетность холдинга за 2016 год, в которой была отражена крупнейшая в российской истории приватизационная сделка — продажа 19,5% «Роснефти» почти за 700 млрд руб. ", "По итогам этой сделки «Роснефтегаз» показал годовой чистый убыток и на этом основании не выплачивал дивиденды в 2017 году.", "\n\nИз отчетности «Роснефтегаза» по РСБУ следует, что общие доходы холдинга (выручка плюс прочие доходы) в 2016 году достигли 1,38 трлн руб., ", "из которых 90% (1,24 трлн руб.) ", "обеспечила сделка по «Роснефти». ", "Выручка составила 800,4 млрд руб. (", "в десять раз больше, чем годом ранее). ", "Но суммарные расходы «Роснефтегаза» — 1,477 трлн руб. — ", "оказались беспрецедентными для компании. ", "В результате холдинг показал убыток до налогообложения 96,2 млрд руб. ", "и чистый убыток 90,4 млрд руб. (", "последний оказался меньше доналогового убытка за счет увеличения отложенных налоговых активов).", "\n\nПродажа 19,5% «Роснефти» отразилась сразу в четырех строках отчета о прибылях и убытках (см. ", "инфографику): доход от продажи, доход от накопленной переоценки акций, себестоимость проданной доли и выплата денег, полученных от продажи акций «Роснефти», в бюджет. ", "Перевод 692,4 млрд руб. ", "в бюджет был отражен в составе прочих расходов, что и позволило показать чистый убыток. ", "Изначально Минфин планировал получить эту выплату в форме дивидендов «Роснефтегаза» (компания на 100% принадлежит Росимуществу).", "\n\nВ соответствии с законодательством и правилами бухгалтерского учета холдинг правомерно отнес перечисленные в бюджет деньги к расходам, объясняют в компании «ФБК Грант Торнтон», которая проводила аудит бухгалтерской отчетности «Роснефтегаза» за 2016 год. «", "Бухгалтерская отчетность АО «Роснефтегаз» во всех существенных аспектах подготовлена в соответствии с правилами составления бухгалтерской отчетности, установленными в Российской Федерации, и учетной политикой общества», — говорится в ответе аудитора на запрос РБК.", "\n\nАналитики и юристы, с которыми говорил РБК, не оспаривают правомерность отнесения 692,4 млрд руб. ", "к прочим расходам (по определению к ним относятся расходы, отличные от расходов по обычным видам деятельности, они не описываются исчерпывающим перечнем), но утверждают, что у компании и государства как ее акционера была альтернатива — выплатить в бюджет дивиденды от продажи акций «Роснефти» и тем самым закрыть год с прибылью «Роснефтегаза», что позволяло бы Минфину претендовать на его дивиденды и в 2017 году.", "\n\nПриватизация с убытком 1. ", "Доход «Роснефтегаза» от продажи 19,5% акций «Роснефти» составил 692,4 млрд руб. — ", "именно за такую цену был продан актив консорциуму Glencore и катарского фонда QIA. ", "2. ", "В составе прочих доходов компания отразила «бумажный» единовременный доход на 550,3 млрд руб., ", "связанный с накопленной ежеквартальной переоценкой по реализованным акциям «Роснефти». ", "3. ", "В «себестоимости продаж» (721,1 млрд руб.) ", "отражены расходы от выбытия 19,5% «Роснефти» по рыночной стоимости этого пакета на конец третьего квартала 2016 года. ", "Если ориентироваться на учетную политику «Роснефтегаза» согласно его отчету за 2014 год (последний опубликованный), себестоимость проданного пакета акций должна была определяться по так называемой рыночной цене 3 (MarketPrice3) на 30 сентября 2016 года, а она составляла 717 млрд руб. ", "4. ", "В прочие расходы включена выплата 692,4 млрд руб. ", "в бюджет от продажи акций «Роснефти». ", "Таким образом, «Роснефтегаз» зафиксировал от операций, связанных с приватизацией «Роснефти», убыток на сумму около 167–170 млрд руб. ", "Фото: Андрей Рудаков / Bloomberg\n\nРасходы вместо дивидендов\n\nВ 2016 году Минфин не раз заявлял, что поступления от приватизации «Роснефти» придут в бюджет именно как дивиденды «Роснефтегаза», а Росимущество потом включило эту сумму (692,4 млрд руб.) ", "в форму 0508022 «Сведения о полученных дивидендах», сообщала Счетная палата.", "\n\nНа практике «Роснефтегаз» в 2016 году выплатил государству 60,6 млрд руб. ", "дивидендов: 36 млрд руб. ", "из прибыли по итогам 2015 года и еще 24,6 млрд руб. — ", "в виде промежуточных дивидендов за девять месяцев 2016 года. ", "Из них к приватизации «Роснефти» имели отношение только 18,4 млрд руб. — ", "ими холдинг компенсировал продажу акций «Роснефти» по более низкой цене, чем изначально планировало правительство.", "\n\nСам «Роснефтегаз» в мае утверждал (.pdf), что в счет дивидендов по итогам 2016 года пошло «ускоренное перечисление» в бюджет всей выручки от продажи доли в «Роснефти». ", "Правительство торопилось с приватизацией 19,5% акций «Роснефти», чтобы успеть закрыть дыру в бюджете, и «Роснефтегаз» перевел деньги в бюджет в тот же день, что и получил их от покупателей доли в «Роснефти» (15 декабря). ", "Выплата была засчитана в расходы компании, по итогам года получен убыток, из-за которого правительство распоряжением от 30 июня 2017 года (в конце августа на него ссылалось Росимущество в письме) освободило «Роснефтегаз» от выплаты дивидендов за 2016 год.", "\n\nЕсли бы «Роснефтегаз» смог выплатить 692 млрд руб. ", "в виде дивидендов, эта цифра не оказалась бы в прочих расходах, а прибыль холдинга, при прочих равных, составила бы около 600 млрд руб. ", "В предыдущие годы «Роснефтегаз» отдавал в бюджет в виде дивидендов от 16 до 25% своей чистой прибыли.", "\n\n692 млрд руб. ", "от продажи акций «Роснефти» могли быть выплачены как дивиденды «Роснефтегаза», считает аналитик АКРА Василий Танурков. «", "Очень странно, что эту цифру отразили в составе расходов», — удивляется он. ", "Если бы эта сумма была отражена как дивиденды, «Роснефтегаз» не показал бы годового убытка, говорит Танурков.", "\n\nАльтернативный сценарий\n\nВопрос в том, мог ли «Роснефтегаз» выплатить такие огромные дивиденды с учетом требований законодательства о дивидендах и правил бухучета? ", "По закону об акционерных обществах дивиденды платятся из чистой прибыли после налогообложения по итогам утвержденной бухгалтерской отчетности за три, шесть, девять или 12 месяцев на основании решения акционеров (в данном случае акционер один — государство в лице Росимущества), напоминает директор экспертной группы VETA Дмитрий Жарский. ", "Но правительство требовало от «Роснефтегаза» денег от продажи акций «Роснефти» непременно до конца 2016 года (до закрытия годового баланса), поэтому дивиденды могли быть только промежуточными — за девять месяцев того года.", "\n\nИсточником дивидендных выплат в том числе может быть нераспределенная прибыль прошлых лет, говорит Жарский, закон это не запрещает. ", "Нераспределенная прибыль «Роснефтегаза» на начало 2016 года составляла 555 млрд руб., ", "следует из ее отчетности, показатель по итогам девяти месяцев 2016 года неизвестен, соответственно, неясно, хватило бы нераспределенной прибыли для перечисления 692 млрд руб. ", "в бюджет именно в форме дивидендов.", "\n\nЗакон об акционерных обществах не определяет ограничения на выплату дивидендов по отношению к величине нераспределенной прибыли, отраженной в бухгалтерском балансе, говорит РБК источник в международной аудиторской компании. ", "При распределении и выплате промежуточных дивидендов возможна ситуация, когда сумма распределяемых дивидендов будет превышать показатель нераспределенной прибыли, утверждает он.", "\n\nДругой собеседник РБК — специалист по бухгалтерскому учету и аудиту в одном из российских вузов — сказал, что если у компании есть реальные денежные ресурсы (у «Роснефтегаза», получившего 692 млрд руб. ", "от покупателей акций «Роснефти», они были. — ", "РБК), дивиденды могут быть выплачены, даже если нераспределенная прибыль уйдет в минус (временно станет непокрытым убытком), и «такое делается на практике».", "\n\nВ законе об акционерных обществах есть ограничение, напоминает источник РБК в международной аудиторской компании: нельзя распределять дивиденды, если в результате этого чистые активы общества станут меньше его уставного капитала. ", "Но, как следует из отчетности «Роснефтегаза», его чистые активы на конец 2015 года составляли около 2,8 трлн руб., ", "на конец 2016-го — более 3 трлн руб., ", "а уставный капитал — около 260 млрд руб., ", "то есть ограничение вряд ли было бы применимо.", "\n\n«Все операции в рамках интегральной приватизационной сделки осуществлялись на основе решений совета директоров АО «Роснефтегаз» в соответствии с директивами правительства РФ и законодательством РФ. ", "Результаты приватизационной сделки нашли свое отражение в бухгалтерской отчетности общества, правдивость которой подтверждена независимым аудитором», — заявили РБК в «Роснефтегазе».", "\n\nРешение о выплате дивидендов принимает акционер — государство, а такого решения (о том, чтобы «Роснефтегаз» выплатил 692 млрд руб. ", "дивидендами) в любом случае не было; в директивах правительства говорилось только о промежуточных дивидендах на 18,4 млрд руб., ", "следовало из сообщения Росимущества от 12 декабря 2016 года (сами директивы не были опубликованы).", "\n\nПресс-служба Минфина не ответила на запрос, в Росимуществе отказались от комментариев. ", "Счетная палата не проводила проверку бухгалтерской отчетности «Роснефтегаза», сказал представитель ведомства." ]

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[ "Q:\n\nnginx repomd.xml 404 Not Found\n\nI set up the nginx repository as specified at http://wiki.nginx.org/Install\n[nginx]\nname=nginx repo\nbaseurl=http://nginx.org/packages/rhel/$releasever/$basearch/\ngpgcheck=0\nenabled=1\n\nWhen I try to install php-fpm, I get the following error\nhttp://nginx.org/packages/rhel/6Server/x86_64/repodata/repomd.xml: [Errno 14] PYCURL ERROR 22 - \"The requested URL returned error: 404 Not Found\"\nTrying other mirror.", "\nError: Cannot retrieve repository metadata (repomd.xml) for repository: nginx. ", "Please verify its path and try again\n\nWhat is another stable baseurl that I can substitute for this?", "\n\nA:\n\nPlease read the instructions completely:\nDue to differences between how CentOS, RHEL, and Scientific Linux populate the\n$releasever variable, it is necessary to manually replace $releasever with either \n\"5\" (for 5.x) or \"6\" (for 6.x), depending upon your OS version. ", "\n\n" ]

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[ "The robbers left three people tied up in a back room as they looted the store, CBS 2’s John Slattery reported. ", "A number of customers were also caught up in the heist. ", "The owners never hit the store’s alarm button, police told reporters, including WCBS 880’s Levon Putney.", "\n\nThe suspects opened the safe and several display cases, and they cleared the place of its jewelry over a period of six or seven minutes.", "\n\nPolice said surveillance video shows two people — what appears to be a man and a woman — run by just as the robbers entered the jewelry store. ", "Gurney said the two people could be potential witnesses who could help in the investigation. ", "He believes the thieves might have told them to leave the area because of a environmental issue.", "\n\nAfter he heard the suspects leave the store, the owner managed to break free of his ties and went to neighboring Buono Bagels and asked its owner to call police.", "\n\n“The guy from next door got loose, came over, banged on the door – ‘Call the police! ", "Call the police! ", "We’ve been robbed!’” ", "said Fred Greenberg, the owner of Buono Bagels. “", "Their mom was there. ", "She had been handcuffed, tied up as well. ", "I cut her loose.”", "\n\nThere were no injuries, and descriptions are vague because of the masks and goggles. ", "One man was in a dark jacket and tie, the other in a blue jumpsuit with a hood.", "\n\nPolice describe the crime as a well-thought out robbery, and said they do not know of another like it in the region.", "\n\nThe amount of the loss has not been determined.", "\n\nRamsey police said they are in touch with the real FBI as they investigate.", "\n\nAnyone with information is asked to call the Ramsey Police Department at (201) 327-2400." ]

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[ "The country needs and, unless I mistake its temper, the country demands bold, persistent experimentation. ", "It is common sense to take a method and try it: If it fails, admit it frankly and try another. ", "But above all, try something., ", "Franklin D. Roosevelt\n\nI'm a Product Development Leader at Ericsson. ", "Ideas and thoughts expressed in this blog are my own personal views and not an endorsement by Ericsson.", "\n\nThursday, 18 May 2017\n\nIn this post I outline the optimal flow for good code reviews. ", "It is important to strictly follow the process to prevent dysfunctional code reviews from taking place and to improve the experience and speed of code reviews for the entire team.", "\n\nThis article does not cover when code reviews should be called in your over all development process. ", "However it applies to any development process that included a code review.", "\n\nA code review always starts with an artefact that is “Ready for Review”. ", "This could be a feature or part of a feature. ", "It will likely include some code updates, some tests (hopefully all automated) and some documentation for end users and/or developers. “", "Ready for Review” means that the artefact is reasonably complete i.e. there is enough completed to do something useful and in the case of code, it executes. ", "It is the author’s call as to when they are ready for review.", "\n\nThe author should look for and appoint two reviewers. ", "You can choose to appoint more reviewers, but two should be sufficient. ", "At least one reviewer should be an experienced developer. ", "You may also be required to appoint a “guardian”.", "\n\nThe reviewers must commit to concluding the review as quickly as possible because we value completed work of the author that is closer to delivery to master, over features that are in progress in the reviewer’s backlog today. ", "Hence the review is always treated as the highest priority task.", "\n\nThe reviewers must read and understand the original “Problem Statement”. ", "What is it that the author is trying to achieve?", "\n\nAll supporting material should also be read and understood. ", "The author may have completed some sort of technical report, design specification, whiteboard diagram of the solution etc. ", "These artefacts should be all used to gain an understanding of the proposed solution. ", "However, absence of these is not a deal-breaker for the review if the solution is the correct one.", "\n\nNext the reviewers should review the tests that are written for the code update. ", "Tests should be well described and their terminology should match the problem domain. ", "Do the tests follow a Given-when-then format? ", "Are the tests correctly coupled? ", "Are they manual or automated? ", "There should be some working tests available prior to reviewing the code.", "\n\nThe author will already have looked at the static analysis tooling and should have removed all the trivial violations as part of getting ready for the review. ", "The reviewers should review any static analysis tooling output. ", "Are there any new failures since the last build? ", "Are there possible hotspots in the proposed solution? ", "Any violations that are entirely reasonable to leave in the code?", "\n\nNow that we have a good understanding of the problem, the overall solution proposed and all the automated static analysis has been done, the reviewers should review the code. ", "All feedback should be ranked as major or minor and logged independently of each reviewer at this stage. ", "Genuine and honest comments should be recorded with consideration for the feelings of the author.", "\n\nNext the Authors and reviewers should come together, supported by tooling, and discuss the feedback that the reviewers have for the Author. ", "For each piece of feedback a decision must be agreed as to whether re-work is required or not. ", "In the exceptional cases where consensus cannot be reached, another senior developer should be brought in to arbitrate. ", "It is reasonable to assume that their decision would be final.", "\n\nThe outcome of the review is a three way decision and it is the reviewers’ call. ", "The code and supporting artefacts can be accepted and merged to master. ", "Alternatively re-work is required. ", "The fact that this option could have serious implications for the project awaiting the output, means that this option needs to be handled professionally and with courage by the Author, the reviewers and the team’s leader. ", "At all times we must be aware of our deadlines and take actions that are pragmatic given the time allowed and the implications for the user or customer.", "\n\nShould minor re-work be required, the author should complete this as soon as possible. ", "A quick glance over the re-work maybe required by the original reviewers to ensure the work is satisfactorily completed, however this is optional and should have been clearly stated by the reviewers at the decision stage.", "\n\nIf substantial re-work is required, the story or task should be brought back to the beginning and any shortcomings addressed using the hands-on help of more senior developers or a mentor. ", "It is preferable to assemble the same reviewers when the code is ready for review again as these reviewers already have an awareness of the problem being addressed. ", "Otherwise it should be considered a brand new code review.", "\n\nIn summary, this article outlines a simple, but clearly defined flow or set of steps for performing excellent code reviews. ", "Following it strictly will ensure consistent and high quality code reviews in your team, resulting in a better product coming out of your team." ]

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[ "/* Copyright (c) Citrix Systems, Inc. \r\n * All rights reserved. ", "\r\n * \r\n * Redistribution and use in source and binary forms, \r\n * with or without modification, are permitted provided \r\n * that the following conditions are met: \r\n * \r\n * * Redistributions of source code must retain the above \r\n * copyright notice, this list of conditions and the \r\n * following disclaimer. ", "\r\n * * Redistributions in binary form must reproduce the above \r\n * copyright notice, this list of conditions and the \r\n * following disclaimer in the documentation and/or other \r\n * materials provided with the distribution. ", "\r\n * \r\n * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND \r\n * CONTRIBUTORS \"AS IS\" AND ANY EXPRESS OR IMPLIED WARRANTIES, \r\n * INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF \r\n * MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE \r\n * DISCLAIMED. ", "IN NO EVENT SHALL THE COPYRIGHT HOLDER OR \r\n * CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, \r\n * SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, \r\n * BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR \r\n * SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS \r\n * INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, \r\n * WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING \r\n * NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE \r\n * OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF \r\n * SUCH DAMAGE.", "\r\n */\r\n\r\nusing System;\r\nusing System.", "Collections.", "Generic;\r\nusing XenAdmin.", "Network;\r\nusing XenAdmin.", "Controls.", "CustomDataGraph;\r\nusing XenAPI;\r\nusing XenAdmin.", "Core;\r\n\r\nnamespace XenAdmin.", "Actions\r\n{\r\n public class SaveDataSourceStateAction : PureAsyncAction\r\n {\r\n List<DataSourceItem> DataSourceItems;\r\n List<DesignedGraph> Graphs;\r\n IXenObject XenObject;\r\n\r\n private Pool GetPool()\r\n {\r\n return Helpers.", "GetPoolOfOne(Connection);\r\n }\r\n\r\n private Dictionary<string, string> GetGuiConfig()\r\n {\r\n Pool pool = GetPool();\r\n return pool !", "= null ? ", "Helpers.", "GetGuiConfig(pool) : null;\r\n }\r\n\r\n public SaveDataSourceStateAction(IXenConnection connection, IXenObject xmo, List<DataSourceItem> items, List<DesignedGraph> graphs)\r\n : base(connection, Messages.", "ACTION_SAVE_DATASOURCES, Messages.", "ACTION_SAVING_DATASOURCES, true)\r\n {\r\n DataSourceItems = items;\r\n XenObject = xmo;\r\n Graphs = graphs;\r\n }\r\n\r\n protected override void Run()\r\n {\r\n Dictionary<string, string> gui_config = GetGuiConfig();\r\n\r\n if (DataSourceItems !", "= null)\r\n {\r\n foreach (DataSourceItem ds in DataSourceItems)\r\n {\r\n if (ds.DataSource.enabled !", "= ds.", "Enabled)\r\n {\r\n Host host = XenObject as Host;\r\n VM vm = XenObject as VM;\r\n if (host !", "= null)\r\n {\r\n if (ds.", "Enabled)\r\n XenAPI.Host.record_data_source(Session, host.opaque_ref, ds.", "DataSource.name_label);\r\n else\r\n XenAPI.Host.forget_data_source_archives(Session, host.opaque_ref, ds.", "DataSource.name_label);\r\n }\r\n else if (vm !", "= null)\r\n {\r\n if (ds.", "Enabled)\r\n XenAPI.VM.record_data_source(Session, vm.opaque_ref, ds.", "DataSource.name_label);\r\n else\r\n XenAPI.VM.forget_data_source_archives(Session, vm.opaque_ref, ds.", "DataSource.name_label);\r\n }\r\n }\r\n\r\n if (ds.", "ColorChanged)\r\n {\r\n if (gui_config !", "= null)\r\n {\r\n string key = Palette.", "GetColorKey(ds.", "DataSource.name_label, XenObject);\r\n string value = ds.", "Color.", "ToArgb().ToString();\r\n\r\n if (!", "gui_config.", "ContainsKey(key))\r\n gui_config.", "Add(key, value);\r\n else\r\n gui_config[key] = value;\r\n }\r\n }\r\n }\r\n }\r\n\r\n Dictionary<string, string> new_gui_config = new Dictionary<string, string>();\r\n string uuid = Helpers.", "GetUuid(XenObject);\r\n\r\n // build new gui config dictionary:\r\n // add keys not related to current XenObject\r\n if (gui_config !", "= null)\r\n {\r\n foreach (string key in gui_config.", "Keys)\r\n {\r\n bool isMatch = (Palette.", "LayoutKey.", "IsMatch(key) || Palette.", "GraphNameKey.", "IsMatch(key));\r\n if (isMatch && key.", "Contains(uuid))\r\n continue;\r\n new_gui_config.", "Add(key, gui_config[key]);\r\n }\r\n }\r\n\r\n if (Graphs !", "= null)\r\n {\r\n // add current XenObject keys\r\n for (int i = 0; i < Graphs.", "Count; i++)\r\n {\r\n string key = Palette.", "GetLayoutKey(i, XenObject);\r\n string value = Graphs[i].ToString();\r\n\r\n // 'key' should not exist in the new gui config dictionary\r\n new_gui_config.", "Add(key, value);\r\n\r\n key = Palette.", "GetGraphNameKey(i, XenObject);\r\n value = Graphs[i].DisplayName;\r\n if (value !", "= String.", "Empty)\r\n {\r\n new_gui_config.", "Add(key, value);\r\n }\r\n }\r\n }\r\n\r\n XenAPI.Pool.set_gui_config(Session, GetPool().opaque_ref, new_gui_config);\r\n }\r\n }\r\n}\r\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nIs it possible to calculate the sum of each group in a table without using group by clause\n\nI am trying to find out if there is any way to aggregate a sales for each product. ", "I realise I can achieve it either by using group-by clause or by writing a procedure. ", "\nexample:\n Table name: Details\n Sales Product\n 10 a\n 20 a\n 4 b\n 12 b\n 3 b\n 5 c\n\nIs there a way possible to perform the following query with out using group by query\nselect \n product, \n sum(sales) \nfrom \n Details \ngroup by \n product \nhaving \n sum(sales) > 20\n\nI realize it is possible using Procedure, could it be done in any other way?", "\n\nA:\n\nYou could do\nSELECT product,\n (SELECT SUM(sales) FROM details x where x.product = a.product) sales\nfrom Details a;\n\n(and wrap it into another select to simulate the HAVING).", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "1. ", "Introduction {#sec1-viruses-09-00064}\n===============\n\nTumor necrosis factor-α (TNF) was first described as a glycoprotein induced in response to endotoxin (the old name of which was cachectin) and has the capacity to kill tumor cells \\[[@B1-viruses-09-00064]\\]. ", "Then, TNF was shown to be a T helper type 1 (Th1) cytokine produced by several cell types, including monocytes/macrophages and T-cells, and to be involved in proinflammatory responses like interleukin (IL)-1β and IL-6 \\[[@B2-viruses-09-00064]\\]. ", "TNF exerts its effects by binding as a trimer to two cell membrane TNF receptors (TNFRs), TNFR1 (55-kDa) and TNFR2 (75 kDa) \\[[@B2-viruses-09-00064]\\]. ", "In concert with chemokines, TNF and TNFRs are involved in the regulation of inflammatory processes like arthritis, of infectious diseases including HIV infection, and of malignancies, since chronic inflammation has been recognized to play a major role in carcinogenesis \\[[@B3-viruses-09-00064],[@B4-viruses-09-00064],[@B5-viruses-09-00064]\\].TNF was first recognized at the protein level, followed by identification of its cDNA sequence \\[[@B4-viruses-09-00064],[@B6-viruses-09-00064],[@B7-viruses-09-00064]\\]. ", "TNFRs are composed of an extracellular domain common to all TNFR superfamily members, a typical cysteine rich motif, and intracellular domains with distinct motifs, allowing the accomplishment of various intracellular functions \\[[@B8-viruses-09-00064],[@B9-viruses-09-00064]\\]. ", "Death receptors are members of the TNFR superfamily characterized by a cytoplasmic region, the death domain, that enables the receptors to trigger pro-death signals within the cell \\[[@B4-viruses-09-00064]\\]. ", "TNFR1 possesses a death domain, and TNFR2 lacks one. ", "This allows TNF to deliver distinct intracellular signals after binding to its receptors. ", "We will discuss in this review how the binding of TNF to its receptors modulates the cellular activation, the interaction between human immunodeficiency virus 1 (HIV-1) proteins, and TNF/TNFR signaling, and the role of TNF/TNFRs in the modulation of the viral life cycle. ", "In addition, we will address the impact of the TNF/TNFR pathway on the immune activation and the formation of viral reservoirs during the course of HIV-1 infection. ", "The opportunity to modulate the TNF effect and the TNFR pathway by anti-TNF therapy and/or to stimulate viral reactivation by TNF or TNF inducers to purge the HIV-1 reservoir will be discussed.", "\n\n2. ", "TNF/TNFR Signaling {#sec2-viruses-09-00064}\n=====================\n\nMany cell types, especially immune cells, produce TNF in response to pathological conditions such as inflammation and infection, including: activated macrophages and T lymphocytes, natural killer (NK) cells, mast cells, and fibroblasts \\[[@B4-viruses-09-00064],[@B8-viruses-09-00064]\\]. ", "A membrane protein belonging to the ADAM (a disintegrin and metalloproteinase) family, the TNF-α converting enzyme (TACE) cleaves various membrane proteins including the TNF precursor, a 25 kDa plasma bound protein, into a 17 kDa soluble TNF form \\[[@B10-viruses-09-00064]\\]. ", "In their trimeric configuration, both membrane-bound and soluble TNF forms are functional when binding to their receptors. ", "Although both TNF forms can bind to each of the two receptors, they display a dichotomic effect. ", "The plasma membrane associated with 25 kDa TNF binds preferentially to the TNFR2, whereas the soluble 17 kDa TNF interacts with TNFR1 with high specificity \\[[@B11-viruses-09-00064],[@B12-viruses-09-00064]\\]. ", "Several intracellular pathways are triggered by TNF binding to its receptors, including the modulation of the apoptotic pathway, NF-κB stimulation, and the activation of p38 mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) \\[[@B4-viruses-09-00064],[@B8-viruses-09-00064]\\] ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}).", "\n\nA 34 kDa adapter protein called TNFR-associated death domain (TRADD) interacts with the cytoplasmic death domain of TNFR1 through its own death domain in response to the binding of TNF to TNFR1 \\[[@B13-viruses-09-00064]\\] ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}). ", "Further, a Fas-Associated death domain protein (FADD) binds to TRADD and activates apoptosis via the caspase cascade \\[[@B14-viruses-09-00064]\\] ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}). ", "On the other hand, the sequential recruitment of receptor interacting protein (RIP), transforming growth factor (TGF)-β-activated kinase 1 (TAK1), and IκB kinase (IKK) by the TNF receptor associated factor 2 (TRAF2) forms a complex that interacts with TRADD \\[[@B8-viruses-09-00064],[@B15-viruses-09-00064],[@B16-viruses-09-00064]\\]. ", "The phosphorylation of IκB by IKK and its subsequent degradation in the proteasome leads to NF-κB translocation into the nucleus, where it binds to the promoters of genes involved in inflammation, such as TNF, IL-6, IL-8, IL-18, chemokines, and cyclooxygenase-2 (COX-2) genes \\[[@B4-viruses-09-00064],[@B8-viruses-09-00064],[@B15-viruses-09-00064],[@B17-viruses-09-00064]\\] ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}). ", "In addition to stress and growth factors, cellular proliferation can be triggered by TNF binding to TNFR1, followed by activation of the following axis; TRADD, TRAF2-RIP, mitogen-activated protein kinase kinase kinase 1(MEKK1), mitogen-activated protein kinase kinase 7 (MKK7), and JNK, ultimately leading to the activation of the AP-1 transcription factor \\[[@B4-viruses-09-00064],[@B8-viruses-09-00064],[@B18-viruses-09-00064]\\] ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}). ", "Although TNFR2 lacks a death domain, it interacts with TRAF2 and can activate the transcription factors NF-κB and AP-1 ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}). ", "Cell proliferation and survival, activation of regulatory T-cells, and the induction of granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion can be elicited through TNF/TNFR2 signaling \\[[@B19-viruses-09-00064],[@B20-viruses-09-00064],[@B21-viruses-09-00064]\\].", "\n\n3. ", "TNF/TNFRs and HIV-1 Entry {#sec3-viruses-09-00064}\n============================\n\nThe role of TNF in HIV-1 entry has been extensively described, especially in primary human macrophages (Figure 1) \\[[@B22-viruses-09-00064]\\]. ", "In vitro, the primary macrophages infected by HIV-1 or treated with HIV-1 envelope protein gp120 release TNF in culture supernatants \\[[@B23-viruses-09-00064]\\]. ", "A delayed detection of HIV DNA long terminal repeat (LTR) up to 72 h has been observed in macrophages pre-treated by TNF parallel to the downregulation of the CD4 receptor \\[[@B22-viruses-09-00064],[@B23-viruses-09-00064],[@B24-viruses-09-00064],[@B25-viruses-09-00064],[@B26-viruses-09-00064]\\]. ", "Therefore, one explanation for the inhibition of HIV entry into permissive cells by TNF might be the down regulation of the expression of the HIV CD4 receptor and the C--C chemokine receptor type 5 (CCR5) coreceptor on the cell surface \\[[@B24-viruses-09-00064]\\]. ", "In fact, CCR5 downregulation on the cell surface results from the secretion of GM-CSF following the stimulation of macrophages with TNF, which will ultimately result in the inhibition of the entry of CCR5-dependent HIV-1 strains \\[[@B25-viruses-09-00064]\\]. ", "In addition, the binding of TNF to TNFR2 activates NF-κB and favors enhanced secretion of HIV suppressive factors, such as macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and regulated on activation, normal T-cell expressed and secreted (RANTES). ", "These factors also downregulate CCR5 on the cell surface \\[[@B27-viruses-09-00064],[@B28-viruses-09-00064],[@B29-viruses-09-00064],[@B30-viruses-09-00064],[@B31-viruses-09-00064]\\], indicating that the TNF inhibition of HIV entry is mediated through TNFR2 but not TNFR1. ", "However, the inhibition of viral entry is not related to the CD4 downregulation in macrophages. ", "Both surface and total CD4 are downregulated in macrophages at the level of transcription after TNF pretreatment for one to five days \\[[@B23-viruses-09-00064],[@B24-viruses-09-00064]\\]. ", "However, after TNF pretreatment for 2 h, a 75% decrease in virus entry is observed, although the levels of surface CD4 expression are not yet modified. ", "In addition, the surface CD4 downregulation in TNF-treated macrophages is mediated through TNFR1 but not through TNFR2 \\[[@B22-viruses-09-00064],[@B23-viruses-09-00064],[@B24-viruses-09-00064],[@B26-viruses-09-00064]\\]. ", "Therefore, the inhibition of HIV-1 entry into macrophages by TNF is mediated through the TNF-R2 but not through TNF-R1 and is independent of the modulation of surface CD4 expression. ", "Altogether, the downregulation of the CCR5 co-receptor is the main mechanism that inhibits HIV entry into macrophages treated with TNF and is not related to the downregulation of the CD4 receptor. ", "However, we cannot exclude that the inhibition of the HIV-1 entry into macrophages could also result from post-binding steps, which have still to be identified.", "\n\n4. ", "TNF/TNFR Signaling in HIV-1 Infection {#sec4-viruses-09-00064}\n========================================\n\nSeveral intracellular signaling pathways, including NF-κB, JNK, and p38 MAP kinase pathways, are triggered by TNF ([Figure 1](#viruses-09-00064-f001){ref-type=\"fig\"}) \\[[@B32-viruses-09-00064]\\]. ", "Diverse cellular functions are regulated by the members of the p38 family, consisting of p38α, p38β, p38γ, and p38δ, through the phosphorylation of transcription factors such as activator protein 1 (AP-1), activating transcription factor 2 (ATF-2), and cAMP response element binding protein(CREB) \\[[@B33-viruses-09-00064]\\]. ", "The first isoform discovered for its role in endotoxin-induced inflammatory response and osmotic shock is p38α \\[[@B33-viruses-09-00064],[@B34-viruses-09-00064]\\]. ", "Independent or synergistic activation of NF-κB and p38 by TNF can be observed \\[[@B35-viruses-09-00064],[@B36-viruses-09-00064]\\]. ", "Specific signaling pathways leading to the activation of either pro-survival mediators or effectors of cell death can be observed in response to TNF stimulation. ", "By binding to TNFR, TNF activates NF-κB, which promotes cell survival, JNKs, and caspases, which favor cell death. ", "Therefore, an exquisite crosstalk between the two pathways will decide the cellular fate \\[[@B37-viruses-09-00064]\\]. ", "In addition, in HIV-1 infected cells, TNF stimulation will favor the binding of p65/p50 NF-κB and AP-1 complexes to their respective transcription factor binding sites present in the HIV-1 long terminal repeat (LTR) promoter. ", "Thus, TNF-mediated translocation of NF-κB to the nucleus, followed by LTR stimulation, fuels HIV-1 production in chronically infected T-cell lines and promonocytic cell lines, such as the ACH2 and U1 cell lines, respectively \\[[@B38-viruses-09-00064],[@B39-viruses-09-00064],[@B40-viruses-09-00064],[@B41-viruses-09-00064],[@B42-viruses-09-00064]\\]. ", "Although TNF could be a major driver of HIV-1 transcription early in the disease, later on, during the progression of the disease, a T helper Th1/Th2 shift has been described \\[[@B43-viruses-09-00064]\\]. ", "Since Th2 cytokines are mostly immunosuppressive with decreased levels of TNF production at advanced stages of the disease, HIV-1 replication could be sustained by the production of some HIV proteins that mimic TNF activity. ", "We and others reported previously that several HIV-1 proteins, especially viral protein R (Vpr), trans-activator of transcription (Tat), negative regulatory factor (Nef), and envelope glycoprotein gp120, activate signaling pathways that are also triggered by TNF, especially in macrophages (Reviewed in \\[[@B44-viruses-09-00064]\\]) ([Figure 2](#viruses-09-00064-f002){ref-type=\"fig\"}).", "\n\n5. ", "HIV Proteins Interaction with TNFR and Downstream Signaling Pathways {#sec5-viruses-09-00064}\n=======================================================================\n\nVpr encodes a 96-amino acid, 14 kDa protein, which is conserved among HIV-1, HIV-2, and simian immunodeficiency virus. ", "Multiple cellular functions are targeted by Vpr, including the induction of cell cycle arrest in the G2 phase, transactivation of the LTR promoter, nuclear import of preintegration complexes, and modulation of apoptosis. ", "Both pro- and anti-apoptotic roles of Vpr have been described. ", "Vpr triggers apoptosis in infected T-cells through activation of caspases 3/7, 8, and 9 \\[[@B45-viruses-09-00064],[@B46-viruses-09-00064]\\] and by blocking NF-κB activation in myeloid cells \\[[@B47-viruses-09-00064]\\]. ", "In contrast, Vpr expression in the Jurkat cell line has been reported to enhance resistance to TNF-induced apoptosis \\[[@B48-viruses-09-00064]\\]. ", "In addition to these functions, Vpr triggers the mitochondrial dysfunction \\[[@B49-viruses-09-00064],[@B50-viruses-09-00064]\\]. ", "Vpr is critical for HIV replication in non-dividing cells, e.g., macrophages \\[[@B44-viruses-09-00064]\\], but is not required for replication in T-cells. ", "Like TNF, recombinant Vpr activates NF-κB, AP-1, and JNK in primary macrophages and monocytoid U937 cells, resulting in the stimulation of HIV-1 LTR and the subsequent enhancement of viral replication \\[[@B44-viruses-09-00064],[@B51-viruses-09-00064]\\]. ", "Vpr-dependent activation of NF-κB has also been reported in primary T-cells \\[[@B52-viruses-09-00064]\\]. ", "In addition, HIV production is increased by Vpr through toll-like receptor 4 (TLR4) and IL-6 secretion \\[[@B50-viruses-09-00064]\\]. ", "Recently, Vpr has been reported to enhance TNF production by HIV-1-infected T-cells, implicating the cellular proteins TAK1 and damage-specific DNA binding protein 1 (DDB1) in this phenomenon \\[[@B53-viruses-09-00064]\\]. ", "TNF produced by infected cells activates NF-κB in bystander cells and favors viral reactivation from the HIV-1 reservoir \\[[@B53-viruses-09-00064]\\]. ", "Also, enhanced stimulation of HIV-1 LTR results from a synergistic effect of Vpr and Tat \\[[@B54-viruses-09-00064]\\]. ", "A few reports indicate that in some cases Vpr can inhibit NF-κB activation. ", "For example, the inhibition of NF-κB mediated gene expression results from a synergistic action of Vpr and glucocorticoid receptors via a pathway involving the suppressor of poly (ADP-ribose) polymerase (PARP)-1 nuclear trafficking in response to TNF \\[[@B47-viruses-09-00064],[@B55-viruses-09-00064]\\]. ", "Thus, the respective roles of Vpr and TNF on cellular functions and HIV-1 replication are complex and depend on the cell type involved.", "\n\nA close interplay between TNF and HIV-1 Nef is present throughout the progression of the disease \\[[@B56-viruses-09-00064]\\]. ", "The multifunctional 27kDa myristoylated Nef protein triggers NF-κB activation in macrophages and monocytoid U937 cells, favoring the HIV LTR activation in vitro \\[[@B57-viruses-09-00064],[@B58-viruses-09-00064]\\], and the transcription of several genes coding for proinflammatory cytokines and chemokines such as TNF, IL-6, MIP-1α, and MIP-1β \\[[@B59-viruses-09-00064],[@B60-viruses-09-00064],[@B61-viruses-09-00064]\\]. ", "The phosphorylation of several key-signaling molecules, including α/β subunits of IκB kinase, ERK1/2, JNK, and p38, is triggered in macrophages treated with recombinant Nef in vitro \\[[@B60-viruses-09-00064]\\]. ", "Moreover, Nef and TNF synergistically stimulate the HIV-1 replication in monocytic cells and primary macrophages \\[[@B62-viruses-09-00064]\\], and Nef directly interacts with several TRAF proteins (TRAF2, TRAF5, TRAF6) to enhance the HIV-1 replication in macrophages \\[[@B63-viruses-09-00064]\\]. ", "In addition to a plasma membrane(PM)-associated TNF shedding, the secretion of vesicular TNF endosomes has been recently described as an alternative TNF secretion mechanism, where Nef-mediated routing of the TNF alpha-converting enzyme (TACE) ADAM17 into Rab4+ early endosomes and the Rab27+ secretory pathway leads to intracellular proTNF cleavage and secretion of vesicular TNF endosomes \\[[@B64-viruses-09-00064]\\]. ", "For the vesicular TNF endosomal trafficking of disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), neurogenic locus notch homolog protein 1 (Notch1) is required \\[[@B64-viruses-09-00064]\\]. ", "In fact, in exosomes released from cells infected with viruses other than HIV, the presence of viral components has been reported including, among others, components of Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and hepatitis C virus \\[[@B65-viruses-09-00064]\\]. ", "Although the role of vesicular TNF has been less studied so far than its soluble TNF counterpart, T-cell activation, viral replication, and viral reactivation from HIV reservoir are enhanced by exosomes of HIV-1-infected cells through a Nef- and TNF-dependent mechanism \\[[@B66-viruses-09-00064],[@B67-viruses-09-00064]\\]. ", "In addition, exosomes from HIV-1-infected cells containing trans-activation response (TAR) RNA stimulate the production of TNF in primary macrophages \\[[@B68-viruses-09-00064]\\]. ", "Finally, exposure to Nef-containing exosomes released from transfected T-cell lines increases CD4+ T-cell apoptosis \\[[@B57-viruses-09-00064]\\].", "\n\nThe HIV-1 Tat protein is critical for the elongation process during viral transcription, but also activates NF-κB, JNK, p38, and ERK1/2 pathways and thereby could mimic the effect of TNF on cellular gene expression \\[[@B44-viruses-09-00064],[@B69-viruses-09-00064]\\] ([Figure 2](#viruses-09-00064-f002){ref-type=\"fig\"}). ", "Both MyD88 and TIR-domain-containing adapter-inducing interferon-β (TRIF) axes recruit the TLR4 pathway, following stimulation by Tat, and lead to the activation of protein kinase C beta2 isoform, MAP kinase, and NF-κB, thus resulting in enhanced TNF production in monocytes \\[[@B70-viruses-09-00064]\\].", "\n\nThe production of TNF, but also of IL-6, IL-10, and interferon γ, has been reported after the interaction of gp120 with CD4 (Reviewed in \\[[@B71-viruses-09-00064]\\]). ", "The production of TNF is triggered by gp120 in peripheral blood mononuclear cells isolated from HIV-1 infected patients \\[[@B72-viruses-09-00064],[@B73-viruses-09-00064],[@B74-viruses-09-00064]\\], in macrophages treated with gp120 in vitro \\[[@B75-viruses-09-00064]\\], and in animal models \\[[@B76-viruses-09-00064]\\]. ", "The PI3K and MAPK pathways are involved in the increase of TNF production, which is triggered by HIV gp120 \\[[@B75-viruses-09-00064],[@B77-viruses-09-00064]\\]. ", "In HIV-infected patients, a positive correlation between the levels of gp120 and the expression profiles of proinflammatory cytokines, including TNF, has been reported \\[[@B78-viruses-09-00064]\\].", "\n\nThe interaction between macrophage-membrane bound TNF and TNFR2 present on CD8+ T- cells triggers CD8+ T-cell apoptosis \\[[@B79-viruses-09-00064]\\]. ", "Chronic inflammation in HIV-1 infection is characterized by the detection of soluble markers of immune activation, including, among others, neopterin, β2 microglobulin, soluble CD30, TNF, and the soluble TNFR2 (sTNFR2) \\[[@B80-viruses-09-00064]\\]. ", "In symptomatic HIV-infected patients, increased TNF levels are detected in the serum, and elevated levels of sTNFR2 are predictive of disease progression \\[[@B81-viruses-09-00064]\\].", "\n\n6. ", "Anti-TNF Medications {#sec6-viruses-09-00064}\n=======================\n\nIn several chronic inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylitis, juvenile arthritis, psoriatic arthritis, Crohn's disease, and ulcerative colitis, the blockade of TNF signaling is commonly used. ", "Thus, medications such as antibodies or receptors, which target the TNF/TNFR pathway for treating various inflammatory diseases, are now in preclinical or clinical phases of development \\[[@B82-viruses-09-00064],[@B83-viruses-09-00064]\\]. ", "In 1998, the human/murine chimeric antibody, infliximab, was approved. ", "It binds with high affinity to both the soluble and the membrane-bound TNF. ", "It was then followed by etanercept, a TNFR2-fragment cristallizable region (Fc) fusion protein, that acts like a decoy to block TNF \\[[@B84-viruses-09-00064]\\]. ", "In 2002 and 2009, the fully human antibodies adalimumab and golimumab, which bind to TNF, were approved. ", "Moreover, certolizumab pegol was approved in 2008. ", "This anti-TNF monoclonal antibody contains a PEGylated Fab fragment, which targets TNF, with the advantage of being administrated to pregnant women. ", "Thus, pregnant women with autoimmune diseases and in need of anti-TNF therapy can be treated with certolizumab pegol, since polyethylene glycol does not cross the placenta \\[[@B85-viruses-09-00064]\\]. ", "Additionally, the cells involved in inflammation could be lysed by adalimumab and infliximab, since both medications trigger apoptosis and cell cycle arrest in transmembrane TNF-expressing Jurkat T-cells. ", "This could result in immune suppression, thus improving the course of inflammatory diseases, such as Crohn's disease, but with a risk of reactivation of latent tuberculosis in infected patients \\[[@B82-viruses-09-00064]\\]. ", "This negative effect can be prevented by appropriate screening, and HIV-infected patients should be adequately vaccinated when possible and closely monitored for early signs of infection. ", "When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated.", "\n\n7. ", "Anti-TNF Therapy and Control of Immune Activation in HIV-1 Infection {#sec7-viruses-09-00064}\n=======================================================================\n\nAt all stages of HIV-1 infection, increased amounts of TNF can be detected either in the plasma or in the tissues \\[[@B38-viruses-09-00064],[@B86-viruses-09-00064],[@B87-viruses-09-00064]\\]. ", "Even in combination antiretroviral therapy (cART) treated patients with undetectable viremia, immune activation is still present along with increased levels of plasma TNF \\[[@B88-viruses-09-00064],[@B89-viruses-09-00064],[@B90-viruses-09-00064],[@B91-viruses-09-00064]\\]. ", "In HIV-infected patients, the increased viral replication and depletion of CD4+ T-cells could result from enhanced TNF expression \\[[@B92-viruses-09-00064],[@B93-viruses-09-00064]\\]. ", "In addition, TNF impairs CD4+ T-cell-mediated immunological control in chronic viral infection \\[[@B94-viruses-09-00064]\\]. ", "Therefore, in addition to the inhibition of viral replication by cART, new therapeutic approaches, which control TNF production, could be helpful to curtail immune activation in HIV-infected patients. ", "Thus, increased levels of TNF in HIV infection could be counteracted by anti-TNF therapy ([Figure 3](#viruses-09-00064-f003){ref-type=\"fig\"}A).", "\n\nMoreover, the release of soluble TNF receptors (sTNFR1 and sTNFR2), following the membrane-bound TNFR shedding by proteolytic cleavage, can compete with the membrane-bound TNFRs for binding to TNF, thus inhibiting its activity. ", "In addition, the cells could be transiently desensitized to TNF action, due to the decrease in the number of membrane receptor molecules as a result of receptor shedding \\[[@B95-viruses-09-00064],[@B96-viruses-09-00064],[@B97-viruses-09-00064]\\]. ", "Nevertheless, to modulate HIV disease, TNF blocking agents and/or TNF inhibitor therapy could be useful, since HIV infection is characterized by immune activation and inflammation \\[[@B98-viruses-09-00064]\\]. ", "Several years ago the use of thalidomide, a TNF inhibitor, was suggested to reduce the serum TNF level and to control the viral load \\[[@B99-viruses-09-00064],[@B100-viruses-09-00064]\\]. ", "The transcription and biosynthesis of TNF is blocked by LMP-420---(2-amino-6-chloro-9-\\[5(dihydroxyboryl)-pentyl\\] purine---, a purine nucleoside analog, which inhibits the replication of HIV-1 \\[[@B101-viruses-09-00064]\\]. ", "A considerable argument in favor of the use of anti-TNF therapy in HIV-1 infected patients is the safety of its use, since no increase in the mortality rate has been observed \\[[@B102-viruses-09-00064]\\]. ", "Furthermore, reports showed that HIV-1 symptoms are improved in treated patients, even if anti-TNF therapy could favor the immunosuppressive status of the patients and thereby increase the risk of opportunistic infections \\[[@B103-viruses-09-00064]\\]. ", "Anti-TNF therapy (etanercept, infliximab, adalimumab) has been shown to be well-tolerated in HIV-infected patients, with no enhancement of the rate of opportunistic infections, unless they had uncontrolled HIV replication \\[[@B104-viruses-09-00064],[@B105-viruses-09-00064],[@B106-viruses-09-00064],[@B107-viruses-09-00064],[@B108-viruses-09-00064]\\]. ", "Anti-TNF therapy may be helpful for the treatment of autoimmune diseases, without enhancing the plasma viremia in patients whose HIV disease is under control by cART \\[[@B103-viruses-09-00064],[@B109-viruses-09-00064],[@B110-viruses-09-00064]\\].", "\n\n8. ", "Modulation of TNF Activity to Clear HIV-1 Reservoirs {#sec8-viruses-09-00064}\n=======================================================\n\nFor a complete viral eradication in HIV-1 infected patients, the persistence of HIV-1 reservoirs is a major challenge \\[[@B111-viruses-09-00064],[@B112-viruses-09-00064],[@B113-viruses-09-00064]\\]. ", "Even in non-viremic patients that are under cART, the formation of an HIV-1 reservoir could result from the persistent immune activation observed especially in the presence of TNF \\[[@B114-viruses-09-00064]\\]. ", "TNF is a well-known activator of NF-κB, which is required to favor HIV-1 integration and the establishment of latency in CCL19-treated resting CD4+ T-cells \\[[@B115-viruses-09-00064]\\]. ", "Among HIV-1 reservoirs, resting or memory CD4+ T-cells are the main target \\[[@B113-viruses-09-00064]\\]. ", "Macrophages are another important HIV-1 reservoir, due to their resistance to apoptosis with sustained viral growth at low levels \\[[@B116-viruses-09-00064],[@B117-viruses-09-00064]\\]. ", "To eradicate the latent HIV-1 pool, an activation induced purging of HIV-1 in patients receiving cART has long been a proposed mechanism as a 'shock and kill' approach ([Figure 3](#viruses-09-00064-f003){ref-type=\"fig\"}B) \\[[@B118-viruses-09-00064]\\]. ", "TNF has been used to reactivate HIV-1 from latently infected cells, although with limited levels of viral reactivation \\[[@B119-viruses-09-00064]\\]. ", "Although TNF consistently activates latent HIV-1 provirus in J-Lat cells, it is much less effective in primary CD4+ T-cells isolated from aviremic HIV-1 infected patients \\[[@B120-viruses-09-00064],[@B121-viruses-09-00064]\\]. ", "Moreover, toxicity associated with TNF treatment has been observed in some cases \\[[@B122-viruses-09-00064]\\]. ", "Therefore, to purge cellular reservoirs, several new drugs that target the epigenetic regulation of HIV-1 gene expression have been tested ([Figure 3](#viruses-09-00064-f003){ref-type=\"fig\"}B). ", "HIV-1 is synergistically reactivated from latency by a combination therapy, using both TNF and histone deacetylase inhibitors (HDACis) \\[[@B123-viruses-09-00064],[@B124-viruses-09-00064]\\]. ", "HIV-1 transcription is activated by the HDACis such as trichostatin A (TSA), trapoxin (TPX), valproic acid (VPA), and sodium butyrate (NaBut), which favor the remodeling of the single nucleosome (nuc-1) present in the HIV-1 promoter \\[[@B125-viruses-09-00064],[@B126-viruses-09-00064]\\]. ", "In view of the 'shock and kill' paradigm, forced HIV-1 gene expression elicited by HDACis and TNF in the presence of an effective cART regimen may lead to clearance of the pool of latently infected cells \\[[@B119-viruses-09-00064],[@B125-viruses-09-00064],[@B127-viruses-09-00064]\\]. ", "In addition to the direct effect of HDACis on HIV-1 transcription, the enhancement of TNF mediated NF-κB activation by HDACis could result in a sustained delay in IκB alpha cytoplasmic reappearance \\[[@B128-viruses-09-00064]\\]. ", "To reactivate HIV-1 from latency in resting CD4+ T-cells of HIV-infected cART-treated patients, inhibitors of histone methyltransferase (HMTIs) have also been recently shown to be efficient \\[[@B129-viruses-09-00064]\\]. ", "Synergistic activation of HIV-1 expression by HDACi and prostratin, a NF-κB inducer that stimulates TNF production, favors viral reactivation \\[[@B119-viruses-09-00064],[@B130-viruses-09-00064]\\]. ", "Disulfiram also reactivates HIV-1 from latency in parallel to increasing the production of TNF in CD4+ T-cells \\[[@B131-viruses-09-00064],[@B132-viruses-09-00064]\\]. ", "The reactivation potential of prostratin is potentiated when used in combination with P-TEFb-releasing agents such as JQ1 \\[[@B133-viruses-09-00064]\\]. ", "Combining TNF treatment with other HIV-1 reactivating drugs such as HDACis, HMTIs, and prostratin enhances HIV-1 replication and ultimately could lead to the clearance of HIV reservoirs in infected patients under cART \\[[@B134-viruses-09-00064]\\].", "\n\nThe 'shock and kill' paradigm has been challenged due to significant concerns about the feasibility and possible problems of this approach \\[[@B135-viruses-09-00064],[@B136-viruses-09-00064]\\]. ", "A novel paradigm, 'block and lock', has emerged recently and is based on the blockade of HIV reactivation from the latency reservoir to allow the clearance of actively infected cells by the immune system \\[[@B137-viruses-09-00064]\\]. ", "The 'block and lock' paradigm relies on the blockade of HIV reactivation, which could be based on several approaches ([Figure 3](#viruses-09-00064-f003){ref-type=\"fig\"}C). ", "First, treatments that block the signaling pathways involved in HIV-1 reactivation could be useful, including, among others, inhibitors of the mammalian target of rapamycin (mTOR) complex \\[[@B138-viruses-09-00064]\\] and of the AKT pathway \\[[@B139-viruses-09-00064],[@B140-viruses-09-00064]\\], potentially as well as anti-TNF treatments. ", "Anti-TNF therapy could be useful for limiting HIV-1 reactivation from latency through the inhibition of NF-κB, MAPK, and p38 pathways. ", "Second, treatments that limit new HIV-1 integration could also, in time, diminish the size of the reservoir. ", "In addition to inhibitors of integrase and of lens epithelium-derived growth factor (LEDGF)/p75, which limit viral integration \\[[@B141-viruses-09-00064],[@B142-viruses-09-00064]\\], anti-TNF therapy could curtail the size of the HIV-1 reservoir by controlling the cellular activation. ", "Potential reactivation of the remaining reservoir could be subsequently cleared by HIV-specific cytotoxic T-cells (CTLs) ([Figure 3](#viruses-09-00064-f003){ref-type=\"fig\"}C). ", "During the initial differentiation of effector cells into memory CD4+ T-cells, NF-κB activation enhances T-cell survival \\[[@B143-viruses-09-00064]\\]. ", "TNF/TNFR signaling may contribute, through its activation of NF-κB, to the establishment and maintenance of latent HIV-1 reservoirs in memory CD4+ T-cells \\[[@B115-viruses-09-00064]\\]. ", "Additionally, TNF stimulation of Nef-expressing HIV-infected T-cells inhibits CD4+ T-cell apoptosis and thereby could increase the size of the T-cell reservoir \\[[@B144-viruses-09-00064]\\]. ", "Thus, TNF-based therapy could be used to clear HIV-1 reservoirs in HIV-infected patients under cART and treated with latency reversing agents (LRA), which will reactivate a replication-competent provirus, resulting in the expression of viral proteins, such as Nef, at increased levels. ", "In cART-treated patients, anti-TNF therapy could be an interesting approach to favor the clearance of latently infected cells by promoting their apoptosis after stimulation by LRA, in parallel to the action of HIV-specific CTLs.", "\n\n9. ", "Conclusions {#sec9-viruses-09-00064}\n==============\n\nBoth immune activation and viral reservoirs are hallmarks of HIV-1 infection and involve the TNF/TNFR pathway. ", "Thus, modulating TNF/TNFR pathway by new therapeutic approaches could limit immune activation and curtail the size of the HIV-1 reservoir in cART-treated patients with undetectable viremia, with the ultimate goal being to cure HIV-infected patients.", "\n\nThis work was supported by grants from the University of Franche-Comté, the Région Franche-Comté (RECH-FON12-000013), the Agence Nationale de Recherche sur le SIDA (ANRS, n°13543 and 13544), and HIVERA 2013 (EURECA project) to G.H. A.K. is a recipient of a postdoctoral fellowship of the Region Franche-Comté.", "\n\nS.P., A.K., and G.H. wrote the paper.", "\n\nThe authors declare no conflict of interest. ", "The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.", "\n\n{#viruses-09-00064-f001}\n\n{#viruses-09-00064-f002}\n\n{#viruses-09-00064-f003}\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Jeremy Corbyn is not the first leader of the Labour party to have form as a Eurosceptic. ", "Hugh Gaitskell was so fearful of the drive for European political union that he warned about Britain ending a thousand years of history as an independent state. ", "Clement Attlee was no big fan of what was then called the common market either.", "\n\nBut this was all a long time ago. ", "Under a succession of leaders starting with Neil Kinnock, Labour warmed to Europe. ", "In the 1980s, with Thatcherism rampant at home, the party saw Brussels as providing protection from free-market zealotry. ", "In the 1990s, under Tony Blair, the feeling was that globalisation had made the nation state redundant.", "\n\nEven so, a small number of Labour MPs remained unreconciled. ", "They pointed out that Labour’s love affair with Europe began just as Europe’s economic performance started to deteriorate. ", "They opposed the Maastricht treaty that paved the way for the single currency on the grounds that it would create an undemocratic central bank with deflationary tendencies.", "\n\nCorbyn was one member of this band. ", "John McDonnell, now the shadow chancellor, was another. ", "Unlike the majority of their parliamentary colleagues and most trade union leaders, they never bought the idea that being a progressive meant being positive about Europe. ", "They saw nothing especially progressive about mass unemployment, the impact of the common agricultural policy on the developing world, the Transatlantic Trade and Investment Partnership, or the bias towards austerity ingrained in the stability and growth pact. ", "Rather, they saw neoliberalism being hardwired into the European project. ", "As indeed it was.", "\n\nNone of this really mattered until Corbyn became Labour leader two years ago. ", "But since 2015 the maverick outsiders have become the maverick insiders. ", "What’s more, the shambolic state of the Conservatives means that Corbyn and McDonnell could soon be neighbours in Downing Street and responsible for Brexit. ", "Parliamentary arithmetic and the determination of the Tories to avoid another election at all costs makes this unlikely, but these are strange and unpredictable times. ", "What Corbyn and McDonnell think about Europe now counts in a way that it didn’t before.", "\n\nLeavers have come up with no solutions for sorting out the country’s long-term economic problems\n\nBoth men campaigned for remain in the referendum, albeit not with great gusto. ", "Labour’s 2017 manifesto pledged to honour the result of the referendum. ", "The leadership has come down hard on MPs who tabled amendments to the Queen’s speech demanding that Britain stay in the single market. ", "All of which is significant. ", "Corbyn and McDonnell are smart enough to understand the risks of Brexit, but they also see it as an opportunity to push through their own economic agenda. ", "Which is why they are exploring the freedom Brexit would provide for public ownership, lower rates of VAT to help those on the lowest incomes, state aid to support sunrise industries, and fair trade agreements with developing countries.", "\n\nRemainers on the left would argue that there is no need to leave the EU for this to happen, but they are wrong about that for two reasons. ", "The first is that a radical socialist programme that included a different approach to state aid, state ownership, public procurement and managed trade would be deemed illegal under European law. ", "The second is that without Brexit, the impetus for change would quickly dissipate.", "\n\nSo what, say remainers. ", "The status quo is better than Brexit, the baleful consequences of which are already clear from the slowdown in the economy and warnings from banks and transnational firms that they will move at least some of their operations out of the UK unless they get the sort of deal they want.", "\n\nBut the left needs to be very careful about running with the idea that business should be able to veto decisions made by the electorate. ", "If Labour had won the recent election, Corbyn would have had a mandate for extensive nationalisation, ending austerity and higher taxation on companies and the well-off. ", "Big business would certainly have cut up rough about all that. ", "There would have been warnings from the Confederation of British Industry about its members moving thousands of jobs out of the country. ", "Would those calling for a second EU referendum be calling for another general election so voters could think again about supporting such a dangerously radical policy? ", "Probably not.", "\n\nNor, given that Britain has been through the decade from hell, is the idea of a return to the status quo especially attractive. ", "The four freedoms of the single market have made it easier for companies to move money, goods, services and people around the EU, but workers have not benefited. ", "There has been virtually no growth in UK per-capita incomes since the start of the financial crisis in 2007, something that has not happened outside wartime in the modern age.", "\n\nBritain is a low-wage economy with a chronic balance of payments problem. ", "Repeated bouts of de-industrialisation mean there has not been a surplus on manufactured goods since the early 1980s. ", "Growth has become ever more dependent on consumers’ appetite for debt, and the willingness of the Bank of England to make servicing that borrowing as cheap as possible. ", "The UK’s poorer regions are 20 years behind the south-east in terms of living standards.", "\n\nThese problems are not new. ", "They were there long before David Cameron decided to hold an EU referendum, and they will be there regardless of whether Brexit happens or not. ", "Remainers on the left have spent the past year bemoaning the referendum result and have expended a great deal of intellectual energy thinking up ways to hold a second referendum or, failing that, to come up with a Brexit that in effect returns Britain to where it was on 22 June 2016.", "\n\nThey have quite legitimately asked leavers to explain what Britain will look like after leaving the EU. ", "But they have come up with no solutions themselves for sorting out the country’s long-term economic problems. ", "The assumption seems to be that all will be well provided Britain’s supply chains are protected by continued membership of the single market, and the City retains its role as Europe’s premier financial centre. ", "This is sheer fantasy. ", "If membership of the single market were a panacea, Britain would not have the weakest investment record of any G7 country. ", "Nor would it be running such a big trade deficit.", "\n\nCapitalism’s ability to see off its rivals has always been based on the notion that it will make people better off, even if some people benefit more than others. ", "But that pledge has been broken. ", "Historically, profound political change only happens at times of crisis. ", "Without the Great Depression and the second world war, there would have been no Labour landslide in 1945. ", "Without the crisis of the mid-1970s, there would have been no Thatcherism. ", "Without the crash, there would have been no Brexit – and Corbyn would still be a backbencher.", "\n\nAs it is, Labour is now led by somebody who spent years in the political wilderness with a simple message: that there was something inherently rotten about modern capitalism; that there were radical solutions to that malaise; and that Europe was part of the problem, rather than part of the solution." ]

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0.85, "start": 1709 }, { "analysis_explanation": null, "end": 1738, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 1734 }, { "analysis_explanation": null, "end": 1850, "entity_type": "NRP", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 1837 }, { "analysis_explanation": null, "end": 2014, "entity_type": "NRP", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2008 }, { "analysis_explanation": null, "end": 2133, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2127 }, { "analysis_explanation": null, "end": 2166, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2160 }, { "analysis_explanation": null, "end": 2400, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2396 }, { "analysis_explanation": null, "end": 2534, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2529 }, { "analysis_explanation": null, "end": 2566, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 2559 }, { "analysis_explanation": null, "end": 3343, "entity_type": "NRP", "recognition_metadata": { "recognizer_identifier": 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"score": 0.85, "start": 4755 }, { "analysis_explanation": null, "end": 4824, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 4820 }, { "analysis_explanation": null, "end": 4900, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 4893 }, { "analysis_explanation": null, "end": 5083, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5068 }, { "analysis_explanation": null, "end": 5260, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5258 }, { "analysis_explanation": null, "end": 5290, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5282 }, { "analysis_explanation": null, "end": 5412, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5399 }, { "analysis_explanation": null, "end": 5498, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5492 }, { "analysis_explanation": null, "end": 5561, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 5548 }, { "analysis_explanation": null, "end": 5766, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": 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"score": 0.85, "start": 6189 }, { "analysis_explanation": null, "end": 6305, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 6298 }, { "analysis_explanation": null, "end": 6360, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 6358 }, { "analysis_explanation": null, "end": 6792, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 6788 }, { "analysis_explanation": null, "end": 6829, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 6816 }, { "analysis_explanation": null, "end": 7018, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 7013 }, { "analysis_explanation": null, "end": 7204, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 7198 }, { "analysis_explanation": null, "end": 6360, "entity_type": "US_DRIVER_LICENSE", "recognition_metadata": { "recognizer_identifier": "UsLicenseRecognizer_140094861023792", "recognizer_name": "UsLicenseRecognizer" }, "score": 0.3, "start": 6358 } ]

[ "Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL.", "\nThe antifolate drug methotrexate (MTX) is widely used in the treatment of various neoplastic diseases, including acute lymphoblastic leukemia (ALL). ", "MTX significantly increases cure rates and improves patients' prognosis. ", "Despite that it achieved remarkable clinical success, a large number of patients still suffer from treatment toxicities or side effects. ", "Even to this date, chemotherapeutic regiments have not been personalized because of interindividual differences that affect MTX response, especially polymorphisms in key genes. ", "The pharmacological pathway of MTX in cells is useful to identify gene polymorphisms that influence the process of treatment. ", "The aim of this review was to discuss the gene polymorphisms of drug-metabolizing enzymes in the MTX pathway and their toxicities on ALL treatment." ]

{ "pile_set_name": "PubMed Abstracts" }

[ 0, 0, 0, 0, 0, 0, 0 ]

[]

[ "package yaml\n\nimport (\n\t\"bytes\"\n\t\"encoding/json\"\n\t\"fmt\"\n\t\"reflect\"\n\t\"strconv\"\n\n\t\"gopkg.in/yaml.v2\"\n)\n\n// Marshals the object into JSON then converts JSON to YAML and returns the\n// YAML.", "\nfunc Marshal(o interface{}) ([]byte, error) {\n\tj, err := json.", "Marshal(o)\n\tif err !", "= nil {\n\t\treturn nil, fmt.", "Errorf(\"error marshaling into JSON: %v\", err)\n\t}\n\n\ty, err := JSONToYAML(j)\n\tif err !", "= nil {\n\t\treturn nil, fmt.", "Errorf(\"error converting JSON to YAML: %v\", err)\n\t}\n\n\treturn y, nil\n}\n\n// Converts YAML to JSON then uses JSON to unmarshal into an object.", "\nfunc Unmarshal(y []byte, o interface{}) error {\n\tvo := reflect.", "ValueOf(o)\n\tj, err := yamlToJSON(y, &vo)\n\tif err !", "= nil {\n\t\treturn fmt.", "Errorf(\"error converting YAML to JSON: %v\", err)\n\t}\n\n\terr = json.", "Unmarshal(j, o)\n\tif err !", "= nil {\n\t\treturn fmt.", "Errorf(\"error unmarshaling JSON: %v\", err)\n\t}\n\n\treturn nil\n}\n\n// Convert JSON to YAML.", "\nfunc JSONToYAML(j []byte) ([]byte, error) {\n\t// Convert the JSON to an object.", "\n\tvar jsonObj interface{}\n\t// We are using yaml.", "Unmarshal here (instead of json.", "Unmarshal) because the\n\t// Go JSON library doesn't try to pick the right number type (int, float,\n\t// etc.) ", "when unmarshalling to interface{}, it just picks float64\n\t// universally. ", "go-yaml does go through the effort of picking the right\n\t// number type, so we can preserve number type throughout this process.", "\n\terr := yaml.", "Unmarshal(j, &jsonObj)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\n\t// Marshal this object into YAML.", "\n\treturn yaml.", "Marshal(jsonObj)\n}\n\n// Convert YAML to JSON. ", "Since JSON is a subset of YAML, passing JSON through\n// this method should be a no-op.", "\n//\n// Things YAML can do that are not supported by JSON:\n// * In YAML you can have binary and null keys in your maps. ", "These are invalid\n// in JSON. (", "int and float keys are converted to strings.)", "\n// * Binary data in YAML with the !!", "binary tag is not supported. ", "If you want to\n// use binary data with this library, encode the data as base64 as usual but do\n// not use the !!", "binary tag in your YAML. ", "This will ensure the original base64\n// encoded data makes it all the way through to the JSON.", "\nfunc YAMLToJSON(y []byte) ([]byte, error) {\n\treturn yamlToJSON(y, nil)\n}\n\nfunc yamlToJSON(y []byte, jsonTarget *reflect.", "Value) ([]byte, error) {\n\t// Convert the YAML to an object.", "\n\tvar yamlObj interface{}\n\terr := yaml.", "Unmarshal(y, &yamlObj)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\n\t// YAML objects are not completely compatible with JSON objects (e.g. you\n\t// can have non-string keys in YAML). ", "So, convert the YAML-compatible object\n\t// to a JSON-compatible object, failing with an error if irrecoverable\n\t// incompatibilties happen along the way.", "\n\tjsonObj, err := convertToJSONableObject(yamlObj, jsonTarget)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\n\t// Convert this object to JSON and return the data.", "\n\treturn json.", "Marshal(jsonObj)\n}\n\nfunc convertToJSONableObject(yamlObj interface{}, jsonTarget *reflect.", "Value) (interface{}, error) {\n\tvar err error\n\n\t// Resolve jsonTarget to a concrete value (i.e. not a pointer or an\n\t// interface). ", "We pass decodingNull as false because we're not actually\n\t// decoding into the value, we're just checking if the ultimate target is a\n\t// string.", "\n\tif jsonTarget !", "= nil {\n\t\tju, tu, pv := indirect(*jsonTarget, false)\n\t\t// We have a JSON or Text Umarshaler at this level, so we can't be trying\n\t\t// to decode into a string.", "\n\t\tif ju !", "= nil || tu !", "= nil {\n\t\t\tjsonTarget = nil\n\t\t} else {\n\t\t\tjsonTarget = &pv\n\t\t}\n\t}\n\n\t// If yamlObj is a number or a boolean, check if jsonTarget is a string -\n\t// if so, coerce. ", " Else return normal.", "\n\t// If yamlObj is a map or array, find the field that each key is\n\t// unmarshaling to, and when you recurse pass the reflect.", "Value for that\n\t// field back into this function.", "\n\tswitch typedYAMLObj := yamlObj.(type) {\n\tcase map[interface{}]interface{}:\n\t\t// JSON does not support arbitrary keys in a map, so we must convert\n\t\t// these keys to strings.", "\n\t\t//\n\t\t// From my reading of go-yaml v2 (specifically the resolve function),\n\t\t// keys can only have the types string, int, int64, float64, binary\n\t\t// (unsupported), or null (unsupported).", "\n\t\tstrMap := make(map[string]interface{})\n\t\tfor k, v := range typedYAMLObj {\n\t\t\t// Resolve the key to a string first.", "\n\t\t\tvar keyString string\n\t\t\tswitch typedKey := k.(type) {\n\t\t\tcase string:\n\t\t\t\tkeyString = typedKey\n\t\t\tcase int:\n\t\t\t\tkeyString = strconv.", "Itoa(typedKey)\n\t\t\tcase int64:\n\t\t\t\t// go-yaml will only return an int64 as a key if the system\n\t\t\t\t// architecture is 32-bit and the key's value is between 32-bit\n\t\t\t\t// and 64-bit. ", "Otherwise the key type will simply be int.", "\n\t\t\t\tkeyString = strconv.", "FormatInt(typedKey, 10)\n\t\t\tcase float64:\n\t\t\t\t// Stolen from go-yaml to use the same conversion to string as\n\t\t\t\t// the go-yaml library uses to convert float to string when\n\t\t\t\t// Marshaling.", "\n\t\t\t\ts := strconv.", "FormatFloat(typedKey, 'g', -1, 32)\n\t\t\t\tswitch s {\n\t\t\t\tcase \"+Inf\":\n\t\t\t\t\ts = \".inf\"\n\t\t\t\tcase \"-Inf\":\n\t\t\t\t\ts = \"-.inf\"\n\t\t\t\tcase \"NaN\":\n\t\t\t\t\ts = \".nan\"\n\t\t\t\t}\n\t\t\t\tkeyString = s\n\t\t\tcase bool:\n\t\t\t\tif typedKey {\n\t\t\t\t\tkeyString = \"true\"\n\t\t\t\t} else {\n\t\t\t\t\tkeyString = \"false\"\n\t\t\t\t}\n\t\t\tdefault:\n\t\t\t\treturn nil, fmt.", "Errorf(\"Unsupported map key of type: %s, key: %+#v, value: %+#v\",\n\t\t\t\t\treflect.", "TypeOf(k), k, v)\n\t\t\t}\n\n\t\t\t// jsonTarget should be a struct or a map. ", "If it's a struct, find\n\t\t\t// the field it's going to map to and pass its reflect.", "Value. ", "If\n\t\t\t// it's a map, find the element type of the map and pass the\n\t\t\t// reflect.", "Value created from that type. ", "If it's neither, just pass\n\t\t\t// nil - JSON conversion will error for us if it's a real issue.", "\n\t\t\tif jsonTarget !", "= nil {\n\t\t\t\tt := *jsonTarget\n\t\t\t\tif t.Kind() == reflect.", "Struct {\n\t\t\t\t\tkeyBytes := []byte(keyString)\n\t\t\t\t\t// Find the field that the JSON library would use.", "\n\t\t\t\t\tvar f *field\n\t\t\t\t\tfields := cachedTypeFields(t.", "Type())\n\t\t\t\t\tfor i := range fields {\n\t\t\t\t\t\tff := &fields[i]\n\t\t\t\t\t\tif bytes.", "Equal(ff.nameBytes, keyBytes) {\n\t\t\t\t\t\t\tf = ff\n\t\t\t\t\t\t\tbreak\n\t\t\t\t\t\t}\n\t\t\t\t\t\t// Do case-insensitive comparison.", "\n\t\t\t\t\t\tif f == nil && ff.equalFold(ff.nameBytes, keyBytes) {\n\t\t\t\t\t\t\tf = ff\n\t\t\t\t\t\t}\n\t\t\t\t\t}\n\t\t\t\t\tif f !", "= nil {\n\t\t\t\t\t\t// Find the reflect.", "Value of the most preferential\n\t\t\t\t\t\t// struct field.", "\n\t\t\t\t\t\tjtf := t.Field(f.index[0])\n\t\t\t\t\t\tstrMap[keyString], err = convertToJSONableObject(v, &jtf)\n\t\t\t\t\t\tif err !", "= nil {\n\t\t\t\t\t\t\treturn nil, err\n\t\t\t\t\t\t}\n\t\t\t\t\t\tcontinue\n\t\t\t\t\t}\n\t\t\t\t} else if t.Kind() == reflect.", "Map {\n\t\t\t\t\t// Create a zero value of the map's element type to use as\n\t\t\t\t\t// the JSON target.", "\n\t\t\t\t\tjtv := reflect.", "Zero(t.", "Type().Elem())\n\t\t\t\t\tstrMap[keyString], err = convertToJSONableObject(v, &jtv)\n\t\t\t\t\tif err !", "= nil {\n\t\t\t\t\t\treturn nil, err\n\t\t\t\t\t}\n\t\t\t\t\tcontinue\n\t\t\t\t}\n\t\t\t}\n\t\t\tstrMap[keyString], err = convertToJSONableObject(v, nil)\n\t\t\tif err !", "= nil {\n\t\t\t\treturn nil, err\n\t\t\t}\n\t\t}\n\t\treturn strMap, nil\n\tcase []interface{}:\n\t\t// We need to recurse into arrays in case there are any\n\t\t// map[interface{}]interface{}'s inside and to convert any\n\t\t// numbers to strings.", "\n\n\t\t// If jsonTarget is a slice (which it really should be), find the\n\t\t// thing it's going to map to. ", "If it's not a slice, just pass nil\n\t\t// - JSON conversion will error for us if it's a real issue.", "\n\t\tvar jsonSliceElemValue *reflect.", "Value\n\t\tif jsonTarget !", "= nil {\n\t\t\tt := *jsonTarget\n\t\t\tif t.Kind() == reflect.", "Slice {\n\t\t\t\t// By default slices point to nil, but we need a reflect.", "Value\n\t\t\t\t// pointing to a value of the slice type, so we create one here.", "\n\t\t\t\tev := reflect.", "Indirect(reflect.", "New(t.", "Type().Elem()))\n\t\t\t\tjsonSliceElemValue = &ev\n\t\t\t}\n\t\t}\n\n\t\t// Make and use a new array.", "\n\t\tarr := make([]interface{}, len(typedYAMLObj))\n\t\tfor i, v := range typedYAMLObj {\n\t\t\tarr[i], err = convertToJSONableObject(v, jsonSliceElemValue)\n\t\t\tif err !", "= nil {\n\t\t\t\treturn nil, err\n\t\t\t}\n\t\t}\n\t\treturn arr, nil\n\tdefault:\n\t\t// If the target type is a string and the YAML type is a number,\n\t\t// convert the YAML type to a string.", "\n\t\tif jsonTarget !", "= nil && (*jsonTarget).Kind() == reflect.", "String {\n\t\t\t// Based on my reading of go-yaml, it may return int, int64,\n\t\t\t// float64, or uint64.", "\n\t\t\tvar s string\n\t\t\tswitch typedVal := typedYAMLObj.(type) {\n\t\t\tcase int:\n\t\t\t\ts = strconv.", "FormatInt(int64(typedVal), 10)\n\t\t\tcase int64:\n\t\t\t\ts = strconv.", "FormatInt(typedVal, 10)\n\t\t\tcase float64:\n\t\t\t\ts = strconv.", "FormatFloat(typedVal, 'g', -1, 32)\n\t\t\tcase uint64:\n\t\t\t\ts = strconv.", "FormatUint(typedVal, 10)\n\t\t\tcase bool:\n\t\t\t\tif typedVal {\n\t\t\t\t\ts = \"true\"\n\t\t\t\t} else {\n\t\t\t\t\ts = \"false\"\n\t\t\t\t}\n\t\t\t}\n\t\t\tif len(s) > 0 {\n\t\t\t\tyamlObj = interface{}(s)\n\t\t\t}\n\t\t}\n\t\treturn yamlObj, nil\n\t}\n\n\treturn nil, nil\n}\n" ]

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[ "Much like how three (or four) of the major US carriers will be getting the HTC One, China's three carriers will also be receiving the same treatment, according to the country's official device approval database. ", "The three flavors are known as 802w, 802t and 802d, each heading to China Unicom (WCDMA), China Mobile (TD-SCDMA) and China Telecom (CDMA), respectively. ", "For the record, the European version we have is 801n, so perhaps the third digit represents the number of SIM slots featured on the device.", "\n\nThis is certainly the case for the 802w. ", "Earlier today, a Sina Weibo user posted the above photo of said phone with its back cover -- between the two plastic lines -- removed, thus exposing not only its two SIM card slots but also a microSD slot just below the camera. ", "It's worth noting that the European version of the One doesn't come with a removable back cover, let alone a secondary SIM slot or a microSD slot; but at least it has LTE, right? ", "Since Sina Weibo requires you to login before letting you see the post, we've got the full picture for you after the break." ]

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[ "Q:\n\nProve that the dual of the matrix norm $||x||_A = \\sqrt{x^T A x}$ equals its inverse $||x||_A^* = ||x||_{A^{-1}}$\n\nAs per definition in an Introduction to Online Convex Optimization by E. Hazan (\n2015). ", "\nCan't figure out to proof that the dual norm of the following defined matrix norms equals the inverse matrix norm:\n$||x||_A = \\sqrt{x^T A x}$\n$||x||_A^* = ||x||_{A^{-1}}$\n\nA:\n\nSure. (", "I think you're missing two assumptions: one that $A$ is symmetric, and the other that $A$ is invertible. ", "I'll assume these...) \nWe assume $x \\neq 0$, otherwise the result is trivial. ", "\nFirst recall that \n$$\n\\|x\\|_{A}^\\ast := \\sup\\{x^T y : y^T A y \\leq 1\\}\n$$\nSo consider $y = A^{-1} x/\\sqrt{x^T A^{-1} x}$ (the denominator is nonzero since $A$ is full rank and $x$ is nonzero). ", " Note that $y^T A y = 1$, and hence this implies $\\|x\\|_{A}^\\ast \\geq \\sqrt{x^T A^{-1} x}$. \nConversely, note whenever $y^T A y \\leq 1$, we may define $z = A^{1/2} y$, in which case $x^T y = x^T A^{-1/2} z$, where $\\|z\\|_2 \\leq 1$. But then by Cauchy-Schwarz, we have $x^T y \\leq \\|A^{-1/2} x\\|_2 \\|z\\|_2 \\leq \\sqrt{x^T A^{-1} x}$. Passing to the supremum over $y$, we have shown $\\|x\\|_{A}^\\ast \\leq \\sqrt{x ^T A^{-1} x}$. \n\n" ]

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[ "Many modern day household refrigerators are divided into two compartments, typically with a freezer compartment on the top and a fresh food compartment on the bottom. ", "A partition within the refrigerator separates the cabinet into these two compartments, each of which has its own door. ", "It is desirable to incorporate a mullion across the cabinet in front of the partition and secured to the cabinet outer case or housing to provide a pleasing appearance. ", "The separate access doors for the freezer and fresh food compartments normally are hingedly attached to the cabinet outer case. ", "It is important for the proper fit of the doors that the width and rectangularity of the cabinet be properly maintained under normal or designed loads. ", "Typically modern household refrigerators employ a sheet metal outer housing and an inner liner of metal or plastic with foam insulation, such as polyurethane, interposed therebetween. ", "The foam material is introduced into the space between the housing and liner in a liquid/gas form and is then allowed to expand throughout the space and solidify by curing. ", "As the foam expands it exerts a force which tends to cause the cabinet to bow. ", "It is desirable to reinforce the cabinet, particularly at the front where the doors are to be hung, in order to assure that the door openings remain square during the foaming operation.", "\nOnce solid the foam inherently adheres to both the outer case and the inner liner and thus add rigidity to the cabinet structure. ", "This has enabled manufacturers to reduce the thickness of the outer cabinet; however, in some instances the cabinet may tend to deflect due to uneven floors or the force placed on the cabinet by the weight of the doors. ", "Such detection can cause a misalignment of one or both of the doors. ", "Thus it is important to insure that the cabinet, particularly the front portion, remains square.", "\nIt has become a practice to incorporate a number of electrically operated devices in the doors of refrigerators for operation or viewing from the exterior of the refrigerator without opening the door. ", "For example it is quite common to have through the door ice dispensers, ice crushers and water dispensers. ", "Additionally it is becoming more common to have indicator panels and lights mounted on the door to be visible from the outside and inform users of various conditions of the refrigerator and possible malfunctions. ", "All of these devices need electric power. ", "In addition the same basic cabinet may be used for several different models which have many different combinations of door-mounted, electrically powered accessories. ", "It is desirable to be able to install the wiring late in the manufacturing process, particularly after the foam insulation has been formed. ", "This enables model differentiation to accomplished late in the manufacturing process and thus simplifies manufacturing.", "\nThe interior of a refrigerator is maintained at a temperature substantially lower than the exterior of the cabinet and heat transfer tends to cause the exterior of the cabinet around the doors to be sufficiently cool that moisture condenses on the metal wall. ", "The cabinet appears to be \"sweating\". ", "Mullion heaters often are placed within the cabinet just outside the edge of the doors, particularly the door to the freezer compartment, to prevent sweating. ", "Such heaters normally are electrical resistance elements mounted within the outer housing and held in place by the foam insulation. ", "Obviously with such a construction the heating element cannot be replaced. ", "One approach to provide greater assurance of having an operative heater element is to embed two or more elements and have a changeable connection so that, if one becomes inoperative, the electrical connection can be changed to another to continue to provide the heating. ", "This is inefficient from a cost standpoint as the multiple heaters are included in each refrigerator while, in many cases, only one element is ever used. ", "Thus it is desirable to have a cabinet construction wherein the mullion heaters are easily replaced.", "\nAccordingly, by the present invention means are provided to insure that the front of the refrigerator housing particularly the housing door openings remain square during production and operation of the refrigerator and that the cabinet has sufficient strength to support the doors.", "\nAdditionally a cabinet structure is provided which enables electrical wiring easily to be installed late in the manufacturing process for facilitating the use of various door mounted electrically operated accessories.", "\nAdditionally a refrigerator cabinet is provided including means for easy installation and replacement of mullion heaters." ]

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[ "The intestinal bacteria are capable of metabolic transformations which may be critical in the formation or degradation of certain known carcinogens. ", "Various bacteria of the flora are capable of forming nitrosamines from progenator substituted amines and nitrite. ", "The flora is also capable of N-dehydroxylating N-hydroxyfluorenyl-acetamide and N-hydroxyacetamidobiphenyl and thus of converting these proximate carcinogens into a form less likely to exert a carcinogenic effect. ", "The demonstration that reduction of the nitro group in p-nitrobenzoic acid can be attributed exclusively to the activity of the intestinal flora suggests that the flora may have a critical role also in metabolic transformation of carcinogens containing the nitro group. ", "Compounds of interest include the known carcinogens 2-mitrofluorene and 4-nitrobiphenyl and drugs such as metonizdazole and piridazole which, although having a useful therapeutic role, have been implicated in mutagenesis and in some carcinogenesis. ", "The role of the flora in the metabolism of these compounds will be studied by comparing their metabolism in germfree and conventional rats as well as in rats specifically associated exclusively with intestinal bacteria capable of certain metabolic reactions. ", "By examining metabolites of these compounds in the urine and feces of these rats as well as in cultures of isolated bacteria, the role of the flora in the metabolism of these compounds will be clarified. ", "Since the reaction intermediates in the carcinogenic or mutagenic process are unstable and not apt to be found in urine or feces, use will be made of the testor strains of histidine requiring Salmonella mutants developed by Ames. ", "We have found that these mutants can be associated with germfree and gnotobiotic rats. ", "The mutants attain high concentrations in the colon and there register the revertant response which can be detected in the bacteria of the feces when the rats are fed carcinogens. ", "These rats enable metabolic studies of carcinogens to be complemented with a means for detecting reactive intermediates occurring in the colon which may be responsible for the carcinogenic process." ]

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[ "Super tiny and super awesome (imo)! ", "This bento box was made by hand, by me, without the use of molds, down to the tiniest detail. ", "I made the box, painted and glazed it. ", "And then added in some of my favorite bento foods. ", "It has rice (with a small sprinkle of sesame seeds on top), tempura veggies and shrimp, edamame, gyoza (aka potstickers or dumplings), fresh veggies (broccoli and carrots) and a small cup of sauce for dipping. ", "Everything in the box is made from polymer clay. ", "The box itself was made from craft wood. ", "I hand cut and sanded every piece before gluing them together and painting.", "\n\nI turned the box into a pendant after much debate. ", "I couldn't honestly decide whether to make it a pendant or a brooch. ", "Anyway, the pendant measures approximately 1 5/8\" tall by 1\" wide. (", "approx 41mm x 25mm) and is strung on a 24\" (approx 60cm) silver plated ball chain necklace.", "\n\nI think next time, I will just paint little dots on top of the rice for the sesame seeds. ", "It was just impossible to get them tinier than the grains of rice themselves.", "\n\nThis is one of my favorite creations ever. ", "I hope you like it as much as me! ", "Feel free to comment and critique (I love them)." ]

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[ "A two-step quantitative pathogen detection system based on capillary electrophoresis.", "\nRapid identification of bacterial pathogens is important for patient management and initiation of appropriate antibiotic therapy in the early stages of infection. ", "Among the several techniques, capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) analysis combined with small subunit rRNA gene-specific polymerase chain reaction (PCR) has come into the spotlight owing to its sensitivity, resolution, and reproducibility. ", "Despite the advantages of the method, the design of PCR primers and optimization of multiplex PCR conditions remain to be studied so that as many pathogens as possible can be analyzed in a single run. ", "Here we describe a novel two-step technique involving multiplex PCR pathogen detection by CE-SSCP analysis followed by singleplex PCR pathogen quantification by CE-SSCP. ", "Specific PCR primers were designed for optimal separation of their products by CE-SSCP based on molecular weight. ", "PCR conditions were then optimized for multiplex analysis of the targets. ", "Subsequently, detected pathogens were quantified by PCR with specific primers. ", "Eight clinically important strains were simultaneously identified under the optimized conditions. ", "Each individual pathogen was then quantified at a level of sensitivity of tens of cells per milliliter. ", "In conclusion, the two-step pathogen detection method based on CE-SSCP described here allows for sensitive detection of pathogens by multiplex PCR (first step) and quantification by specific PCR (second step). ", "The results illustrate the potential of the method in clinical applications." ]

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[ "Q:\n\nCreate videos programmatically?", "\n\nIs there a way to create videos programmatically in Rails?", "\nAre any of these two options possible:\n\nCreate a movie based on supplied images and soundtrack?", "\nModify an iMovie project in Ruby/Rails somehow? ", "If I have a project already created with transitions, etc. ", "Is there a way I can put in images in placeholder places in the movie?", "\n\nA:\n\nI'm guessing what you're looking for will be built in Ruby, and probably not use any of Rails. ", "\nThe only way that I know how to do this is to create a SWF using Ming.", "\nThere's a pretty good example on how to use it here \n\n" ]

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[ "On New Year’s Day, I joined the Mount Lu Ride sponsored by Red Bull. ", "Because of how busy I had been the last couple months, I really hadn’t been on any medium-range rides. ", "This was a good opportunity for me to get out with some of the riders and meet some new people.", "\n\n05.29.11 On Saturday evening, we found ourselves with some free time + good weather. ", "We decided it was time for our entire family to go on a bike ride. ", "Selah isn’t big enough to sit in the iBert, so she got strapped on my back. ", "Selah enjoyed the side view in between snoozes.", "\n\nI was invited by one of the local bike clubs to go riding on a “Three Province” route. ", "Considering that the local clubs are nowhere as large or as organized as they were back in our old city, I take every chance I can get to ride with them. ", "When I showed up that" ]

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[ "Pro Wrestling Sheet has learned Kalisto recently signed a new WWE contract extension.", "\n\nSources tell us the 33-year-old wrestler, who is currently part of Lucha House Party, has come to terms on a multi-year contract extension with WWE.", "\n\nAs you may recall, Kalisto tweeted last year making it known he had 10 months left on his contract and that he’d become a free agent in early 2020. ", "The tweet caught the attention of his co-worker Braun Strowman who replied saying, “Adios.”", "\n\nSources tell us Kalisto decided to re-sign with WWE because the wrestler feels as though he still has a lot left to accomplish in the company.", "\n\nLet the Lucha House Party commence!" ]

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[ "Garden waste dumping\n\nGarden waste, or green waste dumping is the act of discarding or depositing garden waste somewhere it does not belong. ", " \n \nGarden waste is the accumulated plant matter from gardening activities which involve cutting or removing vegetation, i.e. cutting the lawn, weed removal, hedge trimming or pruning consisting of lawn clippings. ", "leaf matter, wood and soil.", "\n\nThe composition and volume of garden waste can vary from season to season and location to location. ", "A study in Aarhus, Denmark, found that on average, garden waste generation per person ranged between 122 kg to 155 kg per year.", "\n\nGarden waste may be used to create compost or mulch, which can be used as a soil conditioner, adding valuable nutrients and building humus. ", "The creation of compost requires a balance between, nitrogen, carbon, moisture and oxygen. ", "Without the ideal balance, plant matter may take a long time to break down, drawing nitrogen from other sources, reducing nitrogen availability to existing vegetation which requires it for growth.", "\n\nThe risk of dumping garden waste is that it may contain seeds and plant parts that may grow (propagules), as well as increase fire fuel loads, disrupt visual amenity, accrue economic costs associated with the removal of waste as well as costs associated with the mitigation of associated impacts such as weed control, forest fire.", "\n\nCause\nThere are strong links between weed invasion of natural areas and the proximity and density of housing. ", "The size and duration of the community have a direct relation to the density of weed infestation. ", "Of the various means in which migration of exotic species from gardens take place, such as vegetative dispersal of runners, wind born and fallen seed, garden waste dumping can play a significant role. ", "The results of one North German study found that of the problematic population of Fallopia, app. ", "29% originated from garden waste. ", "Of a population of Heracleum mantegazzianum, 18% was found by Schepker to be generated by garden waste (as cited by Kowarik & von der Lippe, 2008) pg 24-25.", "\n\nAn Australia government publication suggest that some of the main reasons for the dumping of garden waste can be attributed to lack of care for the environment, convenience, or a reluctance to pay for the correct collection or disposal of the waste. (", "Environmental Protection Agency [EPA]. ", "2013). ", "People dump garden waste to avoid disposal fees at landfill sites or because they do not want to spend the time or effort disposing of or recycling their waste properly. ", "This activity is carried out by people in all parts of the community, from householders to businesses, such as professional landscapers and gardeners.", "\nThe spread of exotic vegetation can out-compete locally endemic vegetation, altering the composition and structure of an ecosystem.", "\n\nDumping of garden waste in particular facilitates the spread of exotic vegetation into forest remnants via the introduction of seeds and propagules contained within the garden waste. ", "Common selection criteria for home gardeners when choosing plants are often based on ease of propagation, suitability to local environmental conditions and novelty. ", "These specific chosen characteristics increase the chance of plant parts and seeds that are introduced into forested areas becoming a problem.", "\n\nThe three major causes of animal habitat degradation are; the disruption or loss of ecosystem functions, the loss of food resources and loss of resident species. ", "Non-native invaders can cause extinctions of vulnerable native species through competition, pest and disease transportation and habitat and ecosystem alteration.", "\n \nThe dumping of garden waste in nature reserves surrounding and near urban areas increases the risk of fires. ", "The dumped garden waste will eventually dry out creating fuel adding to already fallen debris fuel load on which a fire can thrive and spread on. ", "Garden waste can spread weeds and these weeds build fuel for fires. ", " Dumped garden waste can facilitate higher rates of erosion by smothering natural vegetation cover. ", " With no root systems for stabilisation the top soil is vulnerable to erosion (Ritter, J. 2015), This can add higher levels of sediments, contributing to the siltation of creeks and waterways.", "\n\nIf plant matter gets into waterways it can create reduced oxygen levels through the process of decomposition of green waste such as lawn clippings. ", "This directly upsets the quality of water, affecting fish and aquatic wildlife.", "\nThis dumping of green waste can also lead to the blocking of drainage systems; directly through the build-up of plant debris, and indirectly through the spread of invasive plant species that colonise wet areas, reducing and or changing the flow of waterways. ", "This change in flow, including path and velocity, can alter hydrological cycles, affecting frequency and intensity of floods.", "\n\nImpact\nGreen and garden waste has a direct impact to the visual aesthetics of land and can often attract further illegal dumping.", "\n\nIncreased fire risk\nDumping garden waste in nature reserves and parks surrounding and near urban areas can effect directly and indirectly the existing flora and fauna, as well as human life through the increased risk of fires. ", " The dumped garden waste will eventually dry, creating additional fuel, adding to already fallen debris on which a fire can thrive and spread. ", "Garden waste can spread weeds and these weeds also build fuel for fires. ", "Fires may also spread to the suburban areas where humans can also be impacted by losing their homes from fire, incur injury or death from smoke or burns, and suffer economic loses such as income loss and clean-up costs. ", "Fires can lead to an overall loss of habitat and biodiversity.", "\n\nThreat to biodiversity\nThe invasion of exotic plant species into remnant native forests is a threat to biodiversity. ", "Some impacts of habitat degradation include; when native animals, insects and birds become vulnerable and put at risk; loss of food source for native wildlife; disruption of native plant-animal relationships ie pollination and seed dispersal and disconnection of plant-host relationships. ", "Highly adaptive plants chosen for their ease of cultivation out compete more specialised species. ", "\nWeed invasion of a forest system can change the processes of plant succession (the system of one species replacing another due to disturbance factors), the composition of the plant community and the composition and availability of nutrients. ", "The change in forest composition can lead to loss of unique plant species.", "\nWhen a habitat is destroyed, the plants, animals, and other organisms that occupied the habitat have a reduced carrying capacity so that populations decline and extinction becomes a threat. ", "Many endemic organisms have very specific requirements for their survival that can only be found within a certain ecosystem. ", "The term 'hotspot' is used to describe areas featuring exceptional concentrations of endemic species and facing high potential of habitat degradation. ", "The 25 most significant hotspots contain the habitats of 133,149 plant species (44% of all plant species worldwide; table 1) and 9,645 vertebrate species (35% of all vertebrate worldwide; table 2). ", "These endemics are confined to an expanse of 2.1 million square kilometers (1.4% of land surface). ", "Having lost 88% of their primary vegetation, they formerly occupied 17.4 million square kilometers or 11.8% of land surface.", "\nThe recruitment of alien invasive species may lead to a homogenisation of landscapes. ", "Although increased bio diversity in subregions created by newly introduced species may occur, the displacement of the existing plant species may lead to reduced biodiversity on a global scale.", "\n\nWhen population-level properties that indicate superior competitive ability of the invading species are examined, 13–24 (42–77%) of the species are included, with the majority of species showing traits capable of modifying natural systems at both ecosystem and community/population scales.", "\n\nWaterways quality\nThe dumping of green waste such as lawn clippings can block drainage systems which pollutes water therefore effecting water quality and the health of aquatic plants and animals. ", "Dumped garden waste can add high levels of sediments, reducing the light available for photosynthesis. ", " Dumping also block waterways and roads, cause flooding and facilitate higher rates of erosion by smothering natural vegetation cover.", "\n\nCauses / stakeholders\nIllegal dumping is carried out by all types of people in all parts of the community, from householders to businesses and other organizations. ", "Addressing these motivations will enable strategies to be developed that deal with the root causes, rather than the results, of illegal dumping.", "\n\nSome of the main reasons for this careless disregard for waste can be put down to sheer convenience, lack of care for the environment and also a reluctance to pay for the correct collection or disposal of the waste. ", "The monitoring of illegally dumped garden waste by the community and industries will drive effectual tactics to battle illegal depositing. ", "People dump waste illegally to avoid disposal fees at landfill sites or because they do not want to spend the time or effort disposing of or recycling their waste properly. ", "Alligator weed (Alternanthera philoxeroides (Mart.) ", "Griseb.) ", "is an introduced weed originating from Sri Lanka and is creating major issues throughout the Australia since its introduction into the country. ", "Alligator weed has the potential to affect aquatic and terrestrial biodiversity severely and to cause considerable social and economic costs, particularly in aquatic situations.", "\n\nMitigation\nEducation on the value of biodiversity and the negative effects of weed invasion have been identified as key items in changing current trends. ", "Specific education campaigns on the risks of dumping garden waste could be targeted at high-risk societal groups such as residents of housing in close proximity to reserves as well as members of gardening communities and plant sellers. ", "\nRestricting the selection of garden species in new housing developments adjacent to reserves may reduce the effects of illegal dumping, thereby reducing requirement and associated cost of weed management. ", "Creating habitat for wildlife by planting native plants, making a water source available, provide shelter and places to raise young. ", "Healthy ecosystems are necessary for the survival and health of all organisms, and there are a number of ways to reduce negative impact on the environment. ", "Cultivation of native plant species may benefit not only native plant populations but also native animal populations. ", "For example, Sears & Anderson suggest that native bird species diversity in Australia and North America tend to match the volume and diversity of native vegetation. ", "Crisp also explains the percentage of native insect species in a fauna has been found to be consistent with the percentage of native plant species.", "\n\nComposting is a great way to recycle nutrients back into soils. ", "Mulching the garden with leaves and clippings (BMCC, n.d). ", "\nFostering an appreciation of local natural environmental features and plant species may also help mitigate the issue. ", "as well as the restriction of highly invasive plant species through international policy.", "\n \nUtilization of green waste bins that are provided by some councils or shires that are emptied via curbside collection (BMCC. ", "n.d). ", "The addition of facilities for waste disposal could also improve the issue (DECC. ", "2008). ", " Mitigation may involve governments holding campaigns that show people disposing legally and reporting the consequences for disposing illegally. ", "A way Australian governments are addressing the problem is through the increase of fines in conjunction with better law enforcement. ", " In Australia, fines can be up to $1,000,000 and can also incur imprisonment. ", "The Protection of the Environment Operations Act imposes penalties for offences including polluting waters with waste, polluting land, illegally dumping waste or using land as an illegal waste facility.", "\n\nAustralia\nThe new section of the POEO Act (The Protection of the Environment Operations Act 1997) now imposes further penalties for offences including polluting waters with waste, polluting land, illegally dumping waste or using land as an illegal waste facility (Parrino, Maysaa, Kaoutarani & Salam, 2014). ", "Communities are encouraged to report illegal dumping. ", "In accordance with NSW Illegal Dumping Strategy 2014-16, hefty fines and a maximum jail sentence of 2 years can be handed down to repeat offenders.", "\n\nReferences\n\nCategory:Biodegradable waste management\nCategory:Horticulture and gardening\nCategory:Biological contamination\nCategory:Litter" ]

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[ "Characteristic of the prevalence of J wave in apparently healthy Chinese adults.", "\nThe J wave has been seen in idiopathic ventricular fibrillation, Brugada syndrome, and early repolarization syndrome. ", "Although these conditions share some ECG features, the clinical consequences are markedly different. ", "J wave presentation in healthy subjects is not a rare phenomenon, although its characteristics are poorly understood. ", "The aim of this study was to investigate the prevalence and the characteristics of the J wave in apparently healthy Chinese adults. ", "The study was comprised of 1817 consecutive healthy Chinese subjects undergoing annual routine medical examination from April 2006 to July 2006, including 1131 men and 686 women. ", "Routine medical examination including ECG was performed. ", "J wave was defined as a wave on the ECG that followed the QRS complex with amplitude of at least 0.05 mV for 0.03 sec. ", "The prevalence of the J wave in all subjects was 7.26%. ", "The prevalence of the J wave in males was significantly higher than in females (10.52 vs. 1.89%, p<0.01). ", "The incidence of the J wave in the inferior leads (II, III, avF), right precordial leads (V1-V3), and left precordial leads (V4-V6) was 4.57, 0.50, and 2.20%, respectively. ", "The J wave prevalence in the inferior leads was significantly higher than in the left and right precordial leads (both p<0.05). ", "Moreover, the prevalence of the J wave had a positive correlation with age in all subjects (r=0.78, p<0.01). ", "J wave presentation on the ECG of apparently healthy people is not a rare phenomenon and is more likely to be found in the elderly, in males, and more frequently occurs in the inferior leads than in left and right precordial leads." ]

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[ "PDGF was first recognized as a component of platelet .alpha. ", "granules, which had growth promoting activity for smooth muscle cells and fibroblasts (Heldin and Westermark, Cell Regul 1: 555-566 (7-90)). ", "It has also been implicated in the stimulation of connective tissue-derived cells in vitro (Ostman et al., ", "J. Biol. ", "Chem. ", "263(31): 16202-16208 (11-88)), as the major mitogenic protein for mesenchymal cells (Murray et al., ", "U.S. Pat. ", "Nos. ", "4,889,919 and 4,845,075), and as an inducer of cell multiplication and DNA synthesis in cultured muscle cells, fibroblasts and glial cells (Kelly et al, PCT Application W090/14425 (Nov. 29, 1990)). ", "It has also been shown to be involved in the wound healing response (Ross et al., ", "N. Eng. ", "J. Med. ", "295: 369 (1976)), and may be involved in a causative role for the development of proliferative lesions of artherosclerosis (Ross) supra. ", "Others have suggested that this molecule may be a mediator of tumor development as well as in nonmalignant proliferative disorders (Heldin et al., ", "supra).", "\nThe PDGF molecule has been very well characterized. ", "It is known to exist as a heterodimer of an \"A\" chain and a \"B\" chain, connected to each other via disulphide bonds. ", "The dimer, sometimes referred to as \"PDGF-AB\", has a molecular mass of about 30 KDa. ", "Amino acid sequences are known for both the A and B chains, as shown, e.g., by Murray et al., ", "U.S. Pat. ", "Nos. ", "4,889,919 and 4,845,075, the disclosures of which are incorporated by reference. ", "The mature chains contain slightly more than 100 amino acids, and are about 60% homologous. ", "Heldin et al., ", "supra.", "\nDimers PDGF-AA and PDGF-BB have been produced via recombinant means, and have also been isolated from natural sources (see Murray et al., ", "supra; Heldin et al., ", "supra). ", "The various dimers, or \"isoforms\" differ in functional properties and secretory behavior.", "\nThe mechanism by which PDGF acts on cells has received intensive scrutiny, and it has been established that there are two receptors for PDGF, the \".alpha.\" ", "and \".beta.\" ", "receptors. ", "The .alpha. ", "receptor binds all isoforms, whereas .beta. ", "receptor does not bind PDGF-AA, binds PDGF-AB with low affinity, and PDGF-BB with high affinity (Heldin et al., ", "supra; Ostman et al., ", "supra). ", "The receptor is synthesized as a 140 KDa precursor protein which matures to one of 170 KDa, and the .beta. ", "receptor is recognized as a precursor of 160 KDa, and a mature molecule of 180 KDa. ", "cDNA for both receptors has also been isolated (Heldin et al., ", "supra; Kelly et al., ", "supra).", "\nThe structure of the receptors is linked to their function; both comprise five immunoglobulin like domains (extracellular portion), and intracellular portions containing protein tyrosine kinase domains with characteristic insert sequences which have no homology to kinase domains (Yarden et al., ", "Nature 323: 226-232 (1986); Matsui et al., ", "Science 243: 800-803 (1989); Claesson-Welsh et al., ", "PNAS 86: 4917-4921 (1989). ", "When PDGF binds to these receptors, dimerization of the receptor molecules is induced, followed by kinase activation and autophosphorylation of the receptors (Heldin et al., ", "J. Biol. ", "Chem. ", "264: 8905-8912 (1989); Seifert et al., ", "J. Biol. ", "Chem. ", "264: 8771-8778 (1989); Bishayee et al., ", "J. Biol. ", "Chem. ", "264: 11699-11705 (1989)).", "\nThe many mechanisms with which PDGF is involved and the manner in which it reacts with its receptors suggests further study as to how this interaction can be modified One approach to this type of study involves the use of agonists and antagonists. ", "The molecules, using the definitions employed by Kelly et al., ", "supra, either mimic the effect of PDGF (agonists), or block the interaction of receptor and ligand (antagonists).", "\nThe art has long recognized that agonists and antagonists for various materials exist, and Kelly et al., ", "via their discussion, de facto assumes that these exist for PDGF. ", "Review of the literature indicates, however, that no proteinaceous agonists and antagonists to PDGF are taught. ", "For the reasons described supra, it would be desirable to have such material available.", "\nThe two patents to Murray et all, cited supra discuss potential amino acid substitution of cysteine residues in the monomeric chains, provided that these substitutions do not destroy the biological activity of the molecules. ", "The '919 patent generally teaches modifications of PDGF AA molecules. ", "Neither reference teaches that modified dimers of PDGF have antagonistic activity against wild type PDGF.", "\nIt has now been found that portions of the PDGF chains, i.e., peptides derived therefrom, can be used as both agonists and antagonists. ", "It has also been found that manipulation of the dimeric structure of the PDGF molecule leads to the creation of monomeric molecules which are PDGF agonists. ", "Additionally, it has been found that in dimeric PDGF molecules, there is a \"cross\" bond of the second cysteine of each monomer with the fourth cysteine of the other monomer, and that elimination of one of these bond creates a dimeric molecule which competes with wild type PDGF. ", "PDGF-B agonists comprising amino acids 97-180 of the PDGF-B monomer having the cysteines at amino acid residues 124 and 133 substituted, nucleic acid molecules encoding the agonists, plasmids, transformed host cells, and methods for causing receptor dimerization and autophosphorylation in a cell having PDGF-.beta. ", "receptors on its surface comprising administering the PDGF-B agonist form part of the invention. ", "Also described are new PDGF heterodimers, methods and systems for producing these. ", "These are the key features of the invention described herein, which will be seen from the disclosure which follows." ]

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[ "White House economic adviser Larry Kudlow said Friday that U.S. CEOs like Apple's Tim Cook could and should help the Trump administration to press its trade policy agenda with China.", "\n\n\"Mr. Cook should help us get these trade reforms ... Cook can help us by talking to the Chinese,\" Kudlow said in an appearance Fox Business Friday, adding that other corporate leaders that do in business in China should do the same. ", "He suggested that CEOs in contact with leaders in Beijing could convince them that reform is in their best interest.", "\n\nKudlow, the director of the White House's National Economic Council, was responding to Cook's announcement Wednesday that Apple was downgrading its earnings projections for the first quarter of the year due to weak sales in China, a factor he attributed to the ongoing trade war with the U.S. White House adviser Kevin Hassett predicted on Thursday that other corporations that do business in China would also be taking financial hits.", "\n\nAsked on Fox about Hassett's prediction, Kudlow said the administration wanted to dial down the pressure on China but couldn't do that until Beijing made serious reforms. ", "The corporate leaders could help by making Beijing realize that reform was the best way out. \"", "Our CEOS can work with the Chinese,\" he said.", "\n\nThe Trump administration has set a March 1 deadline to reach a deal with China or else it will increase tariffs on $200 billion worth of goods to 25 percent, up from 10 percent. ", "It has tariffs on $250 billion worth of Chinese goods total. ", "China has responded with tariffs on $120 billion of U.S. goods.", "\n\nOn Friday the administration announced that a delegation of trade officials would be heading to China on Monday to lay the groundwork for talks later this month." ]

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