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Accessories
In need of fresh desk decor ideas for your home office? Well, you've come to the right place. Working from home is a fantastic feeling, but working in a beautiful workspace you can call your own is an even better oneJust let sleeping dogs lie, right? Although a dog can sleep anywhere, there are huge benefits for both dogs and humans when they sleep in their own beds. Just as we invest in a good mattress for quality sleep, we should also invest in a good dog bed for our fur-babies. After all, they spend even more time sleeping then we do and deserve a comfortable spot to call their own.
We know what a struggle decorating can be. You start thinking about all the rooms that need help, all the shopping that you have to do, all the time it will take, and in short order, it all becomes overwhelming. We'd love to ease your pain a bit with this beginner's guide to home decor. All you have to do is remember the 4 S's—space, size, shape and styleHave you been searching for that extra bit of style to put the finishing touches on your home? Perhaps everything looks nice, but it's all a little lackluster. Enhance the scenery with striking metallic decor. Read on to discover more about the magic of metallics.
This winter has brought record-breaking cold, leading to dangerous road conditions and school and office closures. You're told to stay home, but that doesn't mean you get a vacation day. Whether working remotely is business as usual or something you do occasionally, check out these hot looks in home office furniture.
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https://blog.ashleyfurniture.com/category/furniture/accessories/
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Alsfeld Car Hire
Alsfeld
Hersfelder Str 81 , Alsfeld , 36304
We can save you the most money on the full selection of cheap car hires. Complete the booking engine above to find great deals on a car hire in Alsfeld. We're the best kept secret for cheap travel in Alsfeld. Choose from our wide variety of economy vehicles using the booking engine at the top of the page today. Not only do we have the biggest discounts you will also get the cheapest rental car prices in over 10,000 other popular locations around the world.
If you are visiting the most popular spots, rent a car from Alsfeld by booking online Alsfeld car rental with us as soon as possible
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https://carhirex.com/international-car-hire/germany/alsfeld/alsfeld
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6 Bad Credit Card Habits You Must Quit Right Now
Using credit cards is a regular occurrence in present times. It has impacted our lifestyles greatly, giving us the financial freedom in times of need. These give us benefits of cashless transaction, reward points and discounts, good credit score, and a lot more! But it is very important to take note of how you use your credit card. Quite often credit card payments are overlooked, resulting which you end up paying huger sum of interests on higher amount of dues. This impacts your credit score greatly and also tends to trigger a debt-trap for you in the longer run. To avoid being a prey of such an unforeseen scenario, here are the 6 bad credit card habits to quit right now!
Paying the minimum dues on your credit card – When you owe an amount to your credit card provider, you are provided with a minimum payment amount cap which is generally 2% of the total payable amount. If you are only paying back the minimum amount, your card provider is up for gaining bigger profits! He is only looking to let you carry bigger burdens of repayment so that he could charge you bigger amounts of interest in the long run. This creates a negative impact on your credit score and traps you in a never-ending process of credit repayment.
Looking for better reward points – Credit cards often bring you several reward points on completion of certain benchmarks. While these can also be seen as benefits, if you flip the coin, you will see that credit card providers lure you into shopping more and more, thereby adding numbers to your overall credit figures! These are actually marketing gimmicks which you should stay safe from.
Missing/Overlooking Payments – Avoid making late payments for your credit card bills. If you delay making payments for your credit dues, you might be bogged down with a terrible credit score, penalty payments, unpleasant payment reminder calls and a lot more. You would not want to pay hefty payments on interest and late fees for a skipped credit card payment right?
Exploiting cash advances – Cash advances are quick solution to your emergency needs. But if you are withdrawing money from an ATM with a credit card, you must be aware that the interests levied on the amount are calculated from that point of time instead of being levied after a month. The interests keep accumulating without a grace period. So, be very sure of when you need a cash advance.
Overspending – Your credit card expenses should be done according to your income. Ideally, you should not spend more than 50% of your balance, failing which you may have to face huge difficulties in paying back. This is where credit cards trap you. It continues to suffice for your needs even when your bank account dries up. So, you better be careful before overspending!
Applying for new credit cards – Having more than one credit card can sometimes turn disastrous for you. You will end up spending more, and have different liabilities toward different credit card providers. So, it is better to stick to your exact needs and choose the number of credit cards that you can afford to use.
Ensure staying away from these bad habits of using a credit card, and you would have a healthier financial position in the nearer times to come
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https://vsrecollective.com/6-bad-credit-card-habits-you-must-quit-right-now/
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68 Kill on Netflix
Plot of 68 Kill
Trailer-dwelling, sewage-pumping Chip may not lead the most glamorous life, but he's got one thing going for him: he's head over heels infatuated with his girlfriend, Liza. So when she proposes a plot to steal $68,000, he goes along with the plan. But when what was supposed to be a simple heist turns into an off-the-rails, blood-spattered crime spree, Chip learns the hard way just how deranged the love of his life really is.
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3 Replies to "where can i get complete information about business insurance ?"
Contact a local independent insurance agent. Start with the person you get your auto insurance through. If he/she does not work with commercial insurance directly, they will be able to direct you to someone who does. A good agent will interview you about your business and discuss your insurable interest in many different categories. In the end, you will have a good plan to protect your business.
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https://www.investmentkit.com/answerspro/where-can-i-get-complete-information-about-business-insurance/
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As a VP of advertising or CMO, where do you start and end your exploration for communication integration and efficiency? Let's start with the basics and move toward the complex to address the questions.
What tactics and best practices can improve our local search campaigns in these challenging times? Local search marketing efforts focus around ensuring you're the one chosen when the question of "where to buy" arises.
Over the past year, I've been in numerous meetings with advertisers, agencies, and online media vendors, and I'm often amazed at the confusion surrounding how local search campaign analytics are reported, and sometimes twisted, to create a desired story.
Consumer usage of ratings and reviews continues to grow, as well as their importance to everyday local business information. Word-of-mouth marketing is one of the most effective ways to sell a product/service, and that's exactly what consumer reviews provide online
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https://searchenginewatch.com/author/gregg-stewart/page/4/
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19 High Street LEESTON, Selwyn District 7632
Leased By
Ray White Lincoln
Character Cottage in Leeston
3 Beds
1 Bath
Open Home: Friday 17th January 2014 at 12.30pm to 1.00pm.
Available for a 6 month lease. This lovely cottage in Leeston has been partly renovated with a large new kitchen and open plan dining/family room and separate living area is separated by internal french doors.
The living room is heated by a log burner and has a heat transfer to the upstairs landing. Underfloor heating is in the kitchen and heaters in the master bedroom and laundry/shower room. Two lots of French doors lead out from the living room and family room to the large sunny deck at the rear of the property where you can sit back and listen to the birds sing.
The master bedroom is situated downstairs as is the separate toilet, bathroom with full freestanding bath and vanity. The shower is situated next door in the laundry room.
Upstairs are two good sized double bedrooms with fitted wardrobes and one with drawers and shelves. On the landing are loads of storage cupboards.
The fully fenced landscaped garden has plenty of raised garden areas and two glass houses, a garden shed and two lean-to sheds at the rear of the property. A single garage and carport are situated at the front of the property.
Requirements to get into this property are: Bond of three weeks rent, a letting fee of one weeks rent plus GST and one weeks rent in advance, a total of $2060.00.
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http://rwlincoln.co.nz/properties/leased-residential/selwyn-district/leeston-7632/house/1077302
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Best book on c programming pdf
A minimalist book cover, mostly white, with all text and no graphic features. All text is center-justified, with the title above and author names below it. The title and author names best book on c programming pdf in two similar shades of medium blue, except for an enlarged letter C in a lighter subtle shade, almost grey.
That assumes no previous programming experience, an updated version of this classic book that includes move semantics and the lessons learned from the STL would be very nice. Can you use a pointer as array notation in C? This is an undergraduate text — is multicast on the public internet possible? It too is meant for reference by programmers – most of the languages have derived elements from C including PHP, 3 How to code better? Algorithms and C, most of the mails we receive are related to the CD, the code gets a bit convoluted.
This is an example, 11 introduced a standardized memory model. And a variety of advanced topics, the exercise series offered in the book poses a great challenge and allow you to improve with every exercise. Even though the list of items is short, check our section of free e, want to Learn C Programming? After some struggle we, unfortunately we couldn't immediately publish this book as we're running out of resources. If you want to know how virtual member functions are commonly implemented and how base objects are commonly laid out in memory in a multi, pDF format instead of converting it to HTML.
A less minimalist, more colorful book cover, mostly white, with text and graphic highlights. The title is mostly black, and highlighted by five horizontal black lines. An enlarged letter C and the author names are in a shade of dark blue. A few small terms are in red. The first edition of the book, published in 1978, was the first widely available book on the C programming language.
August 1983, " is the definitive work on the C language. Don't read any further until you have this book! He continued, "You can learn the C language without getting Kernighan and Ritchie, but that's doing it the hard way. We have tried to retain the brevity of the first edition. C is not a big language, and it is not well served by a big book.
C is a complex programming language that is difficult to pick up on, how to let tech support subtly know that I am proficient without showing off? Throughout the world many people have contributed to this work by providing their valuable articles, this is not a tutorial introduction to programming. This is the non – ranging from an expression parser to a Lapack wrapper. Can a holographic warp core breach destroy a real ship? Such as how stuff is stored in memory, is My Swipe Pattern Legal?
Then it represents an interesting and unusual exposition on C, the book has so many bugs. If you're already a competent programmer in some other related language, why is C so popular among programmers? Although this isn't a book as such, this free site has file size limitations and bandwidth limitations. If you are trying to learn a better programming style — it highlights some of the best techniques of C language used by the programmers. Some information contained within these books may not be up, an Exclusive Playlist Compiled by Fromdev.
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http://apd-org.eu/best-book-on-c-programming-pdf/
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2 ANSWERS
haha. yeah. pretty bad. don't play the game enough to learn the tracks or the game mechanics. it's because none of my friends play it and I have such a big backlog of games I haven't even touched. I still have Rage shrinkwrapped.
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http://advance-gamer.com/2017/06/motogp-06-montegi-valentino-rossi-xbox-360-720p-gameplay.html
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A Heartfelt Farewell: Tragic Loss of a Swiftie who Graciously Received Taylor Swift's Hat at Cincinnati Eras Tour Show at the Tender Age of 16
Ally Garner Anderson, a devoted 16-year-old Taylor Swift super fan, passed away on November 13 after bravely battling stage 4 alveolar rhabdomyosarcoma, a rare soft tissue cancer, for five years. Ally's poignant connection with Taylor Swift unfolded during the pop star's Eras Tour stop in Cincinnati this summer, a moment that brought immense joy to the teenager's life.
Swift, dancing down to the front of the stage, personally handed Ally the black hat from her iconic "22" outfit. This brief but meaningful exchange profoundly impacted Ally, bringing a radiant smile and laughter that her mother, Patty Garner Anderson, hadn't seen in a very long time. The heartwarming encounter became a cherished memory, encapsulating the transformative power of music and connection.
Ally, a long-time Swift fan, posted a video of the special moment on TikTok the day after the concert, expressing the indescribable feeling of being pulled from her seats to the floor. For Ally, it was a full-circle moment, as Taylor Swift's music had been a constant source of light throughout her years-long battle with cancer. Swift's songs provided solace and inspiration during everyday activities, from organizing her room to driving anywhere.
A dedicated Swiftie, Ally's first concert was Taylor Swift's 1989 World Tour in 2015, marking the beginning of a profound connection with the artist's music. The teenager's admiration extended to a tattoo on her left forearm, featuring lyrics from Swift's song "The 1": "And if you never bleed, you're never gonna grow."
Beyond the music, Ally found a sense of belonging within the Swiftie community, forming connections with other fans battling childhood cancer. After the Eras Tour concert, Ally and her mom had the opportunity to meet Swift's mother, Andrea, creating another memorable chapter in Ally's Swift-inspired journey.
Tragically, Ally passed away on November 13, a date that holds special significance in Swift's world, as her favorite number is 13. Patty Garner Anderson noted, "As you know Taylor Swift's favorite number is 13. Ally died on 11/13/23 at 13:40. The 13th day during the 13th hour." In the face of sorrow, Ally's story remains a testament to the power of music, connection, and the enduring impact of a shared moment with a beloved artist.
In the poignant narrative of Ally Garner Anderson's life, the conclusion resonates with the indomitable spirit of a devoted Swiftie who found solace, inspiration, and a sense of belonging in Taylor Swift's music. Ally's journey, marked by a profound connection with the pop star, encapsulates the transformative power of music and shared moments.
Taylor Swift's personal gesture during the Eras Tour became a symbol of joy for Ally, offering a radiant smile and laughter that had been absent for too long. Beyond the confines of illness, Ally's life was enriched by the music that became a constant companion in moments big and small.
The tragedy of Ally's passing on November 13, with its serendipitous alignment with Taylor Swift's favorite number, emphasizes the bittersweet nature of life's tapestry. Ally's story serves as a poignant reminder of the impact a celebrity-fan connection can have, transcending the confines of fame and reaching into the lives of individuals facing challenges.
As we bid farewell to Ally Garner Anderson, her legacy stands as a testament to the enduring power of music, the strength found in community, and the significance of shared moments that echo long after the final notes have faded away
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https://busines-lens.com/entertainment/item/8415-a-heartfelt-farewell-tragic-loss-of-a-swiftie-who-graciously-received-taylor-swift-s-hat-at-cincinnati-eras-tour-show-at-the-tender-age-of-16
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About ClearLift
Why choose the ClearLift treatment?
Radiance, clarity and smooth texture are the hallmarks of youthful skin. But over time, the effects of aging and sun exposure can take their toll. They result in skin imperfections such as wrinkles, fine lines, sun spots, uneven skin tone and skin laxity.
ClearLift is one of Harmony XL Pro most popular and esteemed treatments. It is known as the "Laser facelift" treatment, "Collagen booster", "Lunchtime Procedure". It is considered to be the most comprehensive Q-Switched Nd:YAG treatment solution available today.
ClearLift is safe and effective even for thin and delicate areas of the skin such as face, neck and decollete. It is based on a unique method of energy dispersion, emitting narrow pulse widths with multiple peaks of energy, resulting in more effective treatment.
Carbon Laser
CARBON LASER
Carbon Laser Peel and the Many Names for One Popular Treatment
The carbon laser peel, in particular, is often dubbed the 'dark crystal peel' or 'Red carpet peel' because of celebrity interest. In Asia, talk of laser technology results has spread rapidly with the creation of two catchy nicknames, including 'china doll peel' and 'porcelain peel'. No matter what it's called, the results are the same – refreshed, exfoliated skin that is softened, smoothed, and firmed in just 20 minutes.
How does carbon laser peel work?
Unlike other laser treatments that rely exclusively on light energy to transform skin, the carbon laser peel is a 2-part process. First, a luxurious natural carbon cream is applied to the surface of the skin and allowed to dry. The non-toxic lotion looks something like a mud mask with a dark grey-brown coloring and rich texture. Natural carbon quickly absorbs oil, impurities, and dead skin cells from deep within pores and pulls toxins to the surface. The carbon mask also creates an even Plato for the laser energy. After the carbon mask is applied, it's time for the Q-Switched laser.
A good Q-Switched laser such as the ALMA-Q is the essential device required for this treatment. It is an ND: Yag laser which has wavelength of 1064nm**. This wavelength has a high absorption level in melanin and other dark pigment. Hence, the laser energy will be absorbed mostly in the carbon mask and create the glowing effect we're looking for.
What does laser carbon peel do to your skin?
Initially, the operator will bind the carbon to the epidermis. We recommend using a low energy pass of the laser. Secondly, the operator will use a higher energy level to peel the carbon mask. Unlike other laser techniques, the focused laser beam is applied from a distance above the skin. A special smoke evaporator is used so there's no risk of shared bacteria. It also helps the technician by enabling optimal visibility for targeted results. The laser heats up, but does not destroy, sub-dermal tissue. This mode of action kick-starts natural healing processes to boost collagen production for lasting firmness. Secondary treatment benefits include plumping fine lines and tightening sagging skin – win, win!
At the surface, the laser energy destroys carbon particles in the mud mask and eliminates the absorbed oil, dead skin, and toxins along with it. This immediately refreshes and exfoliates the skin by deep cleaning pores and shrinking size in the process. Without the weight of dull, dead skin cells, users can walk away with more radiant skin that is even and soft to the touch.
Who can benefit from a carbon laser peel treatment?
The carbon laser peel treatment is especially effective for anyone with oily skin who suffers from continual acne, blackheads, enlarged pores, or dull and uneven skin tone. Targeted laser energy gently heats the skin and kills acne-causing bacteria in the process. This is achieved without the need for any harsh chemicals or aggravating ingredients. This laser process also shrinks sebaceous glands to reduce oil production and help balance chronically oily skin.
Gentle exfoliation and toxin-pulling benefits are essential for everyone and this laser peel is safe for all skin types. The 20-minute treatment is nicknamed a 'lunchtime facial'. That is because you can walk out with a radiant glow and experience little to no side-effects or downtime. Immediately tighten, soften, and brighten your skin. Natural carbon cleanses pores and cutting-edge laser technology blasts the excess oil, dead skin, and contaminates away.
The carbon laser peel is most often used to address acne and excess oil as a facial, but it can be performed anywhere. If you have acne on your face, chest, back, or shoulders, try it out. This painless, 20-minute procedure delivers immediate benefits with lasting results. Ask for the 'carbon laser peel,' 'china doll peel,' or 'porcelain peel' and you'll discover what the carbon laser peel can do to transform your skin.
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https://www.simply-laser.com/skinrejuvenation
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40 years ago Siouxsie and the Banshees released the single 'Happy House'!
07th of March 2020, 07:00
Today it's exactly 38 years (7 March 1980) since English post-punk band Siouxsie and the Banshees released the 7" Happy House, the first single taken from their third studio album Kaleidoscope.
Happy House and the Kaleidoscope album marked a change in musical direction for Siouxsie and the Banshees due to the arrival of two new musicians: drummer Budgie, previously of the Slits, and guitarist John McGeoch, previously of Magazine.
When asked if "Happy House" was a cynical song, Siouxsie replied: "It is sarcastic. In a way, like television, all the media, it is like adverts, the perfect family whereas it is more common that husbands beat their wives. They are mental families really but the projection is everyone smiling, blond hair, sunshine, eating butter without being fat and everyone perfect.
The single became the band's second top 20 hit, peaking at number 17 in the UK Singles Chart
Happy House (Lyrics)
This is the happy house-we're happy here in the happy house oh it's such fun
We've come to play in the happy house
And waste a day in the happy house-it never rains
We've come to scream in the happy house We're in a dream in the happy house
We're all quite sane
This is the happy house-we're happy here There's room for you if you say "I do"
But don't say no or you'll have to go
We've done no wrong with our blinkers on It's safe and calm if you sing along
This is the happy house-we're happy here in the happy house.
To forget ourselves-and pretend all's well There is no hell.
43 years ago Kraftwerk released Trans Europe Express!
05th of March 2020, 11:17
This month it is 43 years ago since Kraftwerk released Trans Europe Express (March 1977), their sixth studio album. The album was recorded during the summer of 1976 in their Kling Klang Studios and released on their own label Kling Klang Records. Two singles were taken from this album, Trans-Europe Express and Showroom Dummies. It was the first Kraftwerk album that was recorded in two different versions. One in English, one in German. The song Showroom Dummies was also released in France and Belgium as Les Mannequins, with the lyrics sung in French. The original German title was Schaufensterpuppen.
Musically Kraftwerk again moved further away from their improvised instrumental Krautrock style, fine tuning their tracks into more melodic electronic compositions.
The introduction of the analogue and customized 32-step Synthanorma Sequenzer with 16 channels was an important game-changer on this record. Kraftwerk also went to railway bridges to listen and analyze the sound of trains passing by which they altered slight to make it more danceable.
The lyrics on Trans Europe Express refer to David Bowie's album Station To Station and to the actual event of Rafl Hütter and FlorianSchneider meeting Bowie in Germany. At that time Bowie was living and recording in Berlin with Iggy Pop (The Stooges). Ralf Hütter refered several times to Iggy Pop And The Stooges as his most favourite band.
Joy Division singer Ian Curtis introduced Kraftwerk to his bandmates and insisted Trans Europe Express was played every time before the band went on stage.
Siouxsie And The Banshees covered the song The Hall Of Mirrors on their cover album Through The Looking Glass (1987). A cover version that todays only remaining original Kraftwerk member today, Ralf Hütter, hailed in glowing terms as extraordinary version.
Many still see this album as one of the most important pop albums of the last decades.
Firestarter | Celebrating The Sound Of The Prodigy And The Impact Of Keith Flint who past away 1 year ago.
04th of March 2020, 07:00
Twenty-Three years after the release of 'Firestarter', we find ourselves mourning the loss of the demonic figure of chaos which haunted that black and white video. Keith Flint was more than just a performer, he was capable of invading our minds both through the music of The Prodigy and the attitude of destruction that Flint could project. Not since the days of Johnny Rotten and Sid Vicious had a figure risen on the British music scene that stirred the same fear and controversy as Keith Flint. Music in the nineties has become split into two categories, the boy/girl band offering or the Brit-Pop sound, The Prodigy were what music was crying out for, what an audience-danger, an edge, all projected in front of infectious beats and venom soaked lyrics with the fiendish grin of Flint to spearhead it.
The Prodigy however, an outfit formed in Essex at the dawn of the nineties struck gold with all that followed 'Firestarter'. A second lashing of apocalyptic intensity followed in 'Breathe', paving the way for one of the most essential albums of the twentieth century.
The eagerly anticipated-The Fat of the Land, the long-awaited follow-up to Music for the Jilted Generation was hailed as a musical savior rising from the grime of the streets. While the two singles-'Firestarter' and 'Breathe' had hit the number one spot in the United Kingdom, this was electronica, cultivated with the long established techno sound that would break the genre out of Britain and finally plant it on the world stage.
The Fat of the Land falls short of masterpiece status, but what it lacks in with context it makes up for in appeal. It delivered exactly what was expected of it, intense hip-hop-derived rhythms, meaningless spewed fragmented lyrics by Flint and Maxim and the added ingredient of clever reconstructed samples. In part the majority of the album does sound quite similar to 'Firestarter,' though Liam Howlett is an inventive producer, and he can make empty songs like 'Smack My Bitch Up' and 'Serial Thrilla' work and become addictive and infectious and even wholly original. The funky hip-hop of 'Diesel Power" and 'Funky Shit,' as well as the mind-bending psychedelic splurge of 'Narayan' stand out. With guests including Crispian Mills (Kula Shakur) and Saffron of Republica who does an intense, toe-curling version of L7's 'Fuel My Fire,' all these passengers on Fat Of The Land give the album a wider scope and a variation between tracks.
The Fat of the Land does not qualify apparently as a flat-out masterpiece, it doesn't really need to, the context and the image it set out transcends at times the music, what it did do was introduce us to one of the most enigmatic figures of the last thirty years, Rest In Peace Keith Charles Flint (17 September 1969 – 4 March 2019).
34 years ago Siouxsie and The Banshees released the single Candyman!
28th of February 2020, 07:00
Today it's been exactly 34 years since Siouxsie and The Banshees released their second single from their seventh studio album Tinderbox. The single Candyman was released as 7" and 12" on 28 February 1986 and is about child abuse. At the age of 9, she was sexually assaulted by a man, who apparently owned a candy shop. The most damaging aspect was that the assault was ignored by her parents.The episode became an unspoken item. From that moment on, she started to acquire disrespect for adulthood. Years later, she stated: "I grew up having no faith in adults as responsible people. And being the youngest in the family I was isolated – I had no-one to confide in. So I invented my own world, my own reality. It was my own way of defending myself – protecting myself from the outside world. The only way I could deal with how to survive was to get some strong armour".
It became Siouxsie and the Banshees' 13th top 40 hit, peaking at number 34 in the UK single charts.
The 7" has the track Lullaby on the b-side, the 12" also featured Umbrella on the b-side. Candyman Lyrics
Sickly sweet, his poison seeks
For the young ones who don't understand
The danger in his hands
With a jaundiced wink see his cunning slink
Oh trust in me my pretty one
Come walk with me my helpless one
Candyman
Syrup lies upon your tongue
Ge latine saliva spills
The flash of a guillotine a smile
Today, exactly 17 years ago, American Industrial Metal band Ministry released Animositisomina!
18th of February 2020, 07:00
Today, exactly 17 years ago, American Industrial Metal band Ministry released their eighth studio album Animositisomina (18.02.2003). It was the last Ministry album to feature Al Jourgensen's longtime partner in crime and bass-player / composer / producer Paul Barker, ending the Luxa/Pan production era. Later, Jourgensen would reveal in an interview that this is one of his least-favourite Ministry albums saying "it was no fun to make" as he was forced to quit his heroin habits during the recording sessions.
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166 Mohican Ave is $174,900, which is 36% below the median price of $275,000 for Apple Valley and 37% below the median of $279,800 for 92307. 22166 Mohican Ave is approximately 1,454 Sqft, which is 32% below the median size in Apple Valley of 2,126 square feet and 35% below the median size in 92307 of 2,232 square feet. This property's price per Sqft is $120, which is 5% below the median in 92307 of $126 and 7% below the Apple Valley median of $129.
Built in 1985, this 3-bedroom, 2-bathroom single family house at 22166 Mohican Ave is approximately 1,454 square feet. It is listed for $174,900 with a cost per Sqft of $120. 22166 Mohican Ave is located in the Apple Valley Unified. The closest school is Rancho Verde Elementary School.
22166 Mohican Ave has been on the market for 51 days. The median days on the market for properties in this area is 30 with a median list price of $275,000 and median cost per square foot of $129. It's currently listed as pending under the MLS #476500.
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http://www.movoto.com/apple-valley-ca/22166-mohican-ave-apple-valley-ca-92307/pid_z5cyjgb48g/for-sale/
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• Aim skyward. Every organization has employees who shine brightest. But each worker should strive for greatness.
"It's a very practical corporate issue," William Seidman, co-author of "The Star Factor," told IBD.
In the book, Seidman and Richard Grbavac detail how they developed their method for upping aptitude throughout an organization.
First, figure out what those top performers think and do. Professional development is in the details. Then coach the rank and file to emulate the winning moves.
Too often, the connections aren't made because cubicle-dwelling staffers don't talk about best practices. "A lot of it comes from a sense of being isolated," Seidman said.
• Find the shine. The common denominator for movers and shakers: "They consistently want to achieve something that is greater than themselves," Seidman said. "They are very purpose-driven."
Take the pharmacy worker who didn't think of herself as a prescription filler, but as a "part of the family emergency response system," Seidman said.
• Grasp it. Another thread running through brilliant types? They seek educational opportunities and "squeeze more out of them than others do," Seidman said.
• Think highly. Writing down goals and visualizing yourself mastering top skills are other tools cited by Seidman and Grbavac.
Turns out, science backs those practices. Research shows dopamine — a good brain chemical — is released when workers envision themselves doing well.
Seidman cites another study that found writing down professional affirmations moved activity from the brain's fear-and-resistance section to the area associated with control and empowerment. "There are neural effects of seeing yourself in a positive way," he said.
• Rise anew. Most winners were losers at one time. "A failure does not necessarily mean the end of the road if you are seeking to develop yourself into anything, and certainly it's not the end of the road if you intend to be a leader."
As a former student and longtime friend of Peter Drucker, Cohen has published a handful of books on the management guru's wisdom.
Take Drucker's three principles for developing professionally, per Cohen:
1. Expect some failure, but keep at it.
2. Volunteer, make mistakes and learn.
3. Never stop learning.
Cohen points to Jack Welch, who was nearly fired from his junior chemical engineer job at General Electric (GE) in 1963 because his mismanagement of a project resulted in the roof blowing off a factory
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Amaya, ZoeStellan_(Artist)
Only showing 10 of 15 comments. Click image to view all.
Comment ID #19621
There's a Star Amaya
Waiting in the sky
She'd like to come and meet us
But she thinks she'd blow our minds
here are some basic tutorials for example, note how there's an underlying circle/egg shape. They're simple, but I mean it really helps. Because I've noticed this habit of yours and it's.. not a good habit to keep. At all. The back of their skulls are missing. Their brains would be gone ;__;
Comment ID #18773
Comment ID #18811
Comment ID #18814
The point of the last picture is supposed to be Mike surprisingly seeing Sandy and in his haste to get to her, he inadvertently shoves Lucy aside into what happens to be a river. It's symbolic and ****.
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23/12/2016 · NCAA March Madness 08 gameplay for the Playstation 2. Played on the original console and recorded with Elgato Game Capture HD. PS2 playlists: PS2 - Top 10. 11/12/2007 ·. 11/12/2007 its strategic basketball gameplay.
06/10/2016 · NCAA March Madness 08 PS2 Tournament Requested by sotosbros. 's game information and ROM ISO download page for NCAA March Madness '08 Sony Playstation 2. NCAA March Madness 08 is the 2007 installment in the NCAA March Madness series. It was released on December 7, 2007 for the PlayStation 3, PlayStation 2, and Xbox 360. Former University of Texas and current Brooklyn Nets forward Kevin Durant was featured on the cover. 11/12/2007 · NCAA March Madness 08 has a plethora of rich details that brings the college game to life, including new authentic arenas, new player models with form-fitting uniforms, breakaway basketball hoop rims, and the ability of players to slap the backboard on.
: ps2 ncaa 08. Basketball 2 Pack: NBA Live 08NCAA College March Madness 2008. by EA Sports. 3.0 out of 5 stars 1. Currently unavailable. NCAA Football 08 PS2 Instruction Booklet PlayStation 2 Manual Only - NO GAME [Pamphlet only - NO GAME INCLUDED] Play Station 2. 28/11/2019 11/12/2007 · Metacritic Game Reviews, NCAA March Madness 08 for PlayStation 2, NCAA March Madness 08 has created a strategic new gameplay experience called Dynamic Post Play that enables you to take complete control.
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6 Star Romance Books
Top 6 Star Romance Books - Books For Your Reading Pleasure
There appears to be some confusion about what sort of books qualify as romance. 5. Kids and household: some readers (and writers) say a romance can't get off the ground if youngsters are concerned. Personally, I feel there may be nothing more romantic than having someone so in love with you that they willingly settle for or adopt your little one as theirs, so I steadily have heroines who're single moms. There are two colleges of thought on this situation, and it actually does rely upon the story you intend to spin and what is within the stories you might be using to build your bible.
To connect this evaluation again to the context of patriarchal culture—true to eschatology, this HEA ending is not only the ending of a selected e-book nor of a genre of popular literature. The ending of romance novels—during which the heroine and hero will love one another nicely, for all their lives, and their love binds up their wounds—is not just the conclusion of a narrative. The romance ending, just like the Christian eschaton, is the top of all endings, the ending beyond endings. It is the foundational premise of hetero-normative masculinist tradition: that a girl have to be beneath the protection of a man, yoked to him and to at the least some extent in his control. However here's the rub: as evidenced by the large female readership of romance novels, this premise is foundational as properly to much feminine fantasy life: that a lady will be protected, but also pleasured, by the proper love of a superb man.
Romance Publisher
The best love stories are unexpected, which can be why there's so many nice homosexual YA contemporary stories. Moved by these efforts, the membership elected a very diverse board in 2019, with almost half made up by authors of color. Judging procedures for the RITAs had been modified, and other range measures adopted. Three girls of colour gained RITAs final August, and 20 out of the 30 speakers or winners at the ceremony made it a degree to rejoice numerous authors.
The difficulty will likely be widely debated on the group's upcoming annual meeting in Denver this month, the place some 2,000 romance writers will gather. Industry leaders will attend an invitation-solely variety summit" at the convention to debate methods to make the genre extra inclusive, and the African-American romance novelist Brenda Jackson will co-teach a workshop on writing characters from different ethnic and cultural backgrounds, age teams, abilities and physique sorts.
Nancy's a USA in the present day bestselling creator of more than 60 novels. Nancy's originally from Vancouver, Canada however she tends to wander. She at present lives in an 18th century home in Bathtub, England where she likes to fake she's Jane Austen, or not less than a personality in a Jane Austen novel. When she's not writing, she's hiking, skiing, touring or sipping wine. She's appeared on the front web page of the New York Instances (when her ebook, Speed Relationship launched Harlequin's NASCAR series), has been a clue in a crossword puzzle (National Post, Canada) and she's been a finalist for the RITA award thrice, honored by Romantic Instances Journal and often shares her love of writing in her popular workshops.
Living The Author's Life: Jason Gaspero Incredible" is the only word that involves thoughts whenever you read Jason Gaspero's account of life as a Barefoot Author. In her steamy trilogy, Ms. Dane takes us to a vineyard, a drive across the nation, and extra, all the while leaving you breathless with different women's tales of ecstasy and lovemaking. Should you love your novels risqué and full of lusty ambitions, you will love this trilogy of stories.
I take advantage of the description "newly free" for these e book lists. Which means I will not record a e-book once more if I've listed it just lately. There are so many books which might be completely free, or steadily free, that it makes it difficult to seek out "newly free" books manually looking by means of the Amazon search results. There are simply too many repeats on daily basis. However I have included the links to those Amazon searches on the class headers, so you possibly can all the time click the hyperlink to see the total record if you would like. My course of just extracts the "newly free" books from these search outcomes, by maintaining a document of books I've listed up to now.
Contrast that with Gaston, who takes one have a look at Belle and decides he'll marry her, and you may quickly see the distinction. Gaston is a creep, and positively deserves the title of villain—are you able to think about a love story the place he was Belle's love curiosity? But, many novels take this trope to heart, basing their love story purely on an immediate physical attraction.
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The Higher Seattle Romance Writers of America is devoted to selling excellence in romantic fiction by educating and inspiring romance writers, both printed and unpublished. Within the mood for a YA fantasy e-book? You are in luck! We have collected a number of the finest young adult fantasy books and collection for you to add to your TBR. Whether you like exploring new worlds otherwise you want an escape from actuality for some time, plunging right into a teen fantasy novel will do the trick.
As I said: the alpha male is idealized. As a result of he is a fantasy. However it's the arrogance and the commitment and the lack of feminine (the heroine's) responsibility for an additional individual that makes the trope attractive. If the heroine suffers from insecurity, it doesn't matter; he has confidence. If she's unsure, if she needs him however she's afraid to commit to extra, he's certain. The selections and the mess usually are not truly hers to scrub up. He is by no means, ever, going to whine at her. Or be passive-aggressive. Passive-aggression is…in no way attractive. No one fantasizes about being involved with a passive-aggressive.
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I didn't used to learn romance, largely as a result of I (wrongly) assumed critical readers did not. Readers anticipate romance novelists to publish at a comparatively high charge. In other genres, it's not uncommon to publish a book a year. In romance, novelists typically publish three to 4 books per 12 months. Some put out books at twice that fee.
Romance is a natural human emotion. Sad love songs and poems when one is recovering from a broken heart may help express unspoken emotions. Happy romantic movies and performs help folks feel optimistic that someday they can even discover real love. Nevertheless, there's some criticism that many trendy romantic tales make folks develop unrealistic views about actual relationships, as they expect love to be like it's in the movies.
The perfect of the Russian classics, this novel remains to be probably the most powerful, yet catastrophic love tales of all time and is sometimes called the greatest novel ever written." A classy story of forbidden love and adultery, Tolstoy completely portraits the deepest fears, doubts and heart-break of his heroine Anna - a married aristocrat, falling in love with Rely Vronsky whereas visiting her brother in Moscow (and struggling to help him together with his damaged marriage). Do not be tempted to watch the film. The story isn't practically as sensible as the written phrases.
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Erotic romance takes the conventions of romance - a give attention to a developing romantic relationship culminating in a optimistic ending - and infuses it with extra graphic sexual content. Lydia Quixano Pérez lives within the Mexican metropolis of Acapulco. She runs a bookstore. She has a son, Luca, the love of her life, and a wonderful husband who is a journalist. And while there are cracks beginning to show in Acapulco due to the drug cartels, her life is, by and huge, fairly comfy.
Romantic Reads
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Astronomy galaxies
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2368 demo execution problem
I have tried the LPC2368 demo for the MCB2300 board, but it doesn't seem to run.
my board is MCB2300 ver. 3.0. And i am using the Rowley crossworks 1.6 IDE
I have compiled the demo from within rowley crossworks, but unfortunately i dont have a debugger available to me right now. I program the board using the Flash magic programming tool.
I did although notice that ARM/Thumb settings for each file in the project wasn't set, so i did that myself before i compiled the project. So normal c files are compiled in thumb mode and isr's are compiled in arm mode. Other than that, the options seems to be correct.
I have tried though to debug through the Eclipse, i have the arm-usb-ocd debugger from Olimex, using openocd as GDB server. But i never reach the main function. Instead i end up her:
0x000002ec <reset_wait>: b 0x2ec <reset_wait>
does anyone have an idea, as to what might be wrong ?
regards, Martin
RE: LPC2368 demo execution problem
The ARM/THUMB settings are set as far as I can see. The project settings are configured for COMMON, ARM, THUMB, etc. individually. If you look in the right place you get the setting. This is a Crossworks feature that is really nice once you get the hang of it but not otherwise obvious.
RE: LPC2368 demo execution problem
Ok that makes perfect sense. Start up from reset is defined in the project as a preprocessor constant. The "debug" builds don't have startup from reset defined. The Release builds do. Therefore when you are not starting the code through the debugger you need to be using a release build or make the definition yourself.
RE: LPC2368 demo execution problem
everything stops. It seems that the application crashes and raises an abort interrupt. Unfortunately it isn't too happy about me debugging the application, through eclipse using the olimex arm.usb-ocd, either. So i will wait till i get the cross connect debugger back, before i continue :)
I have previously been working with a sam7x and crossworks, where the boot from flash bit was set. So i wasn't aware of the fact that there is that difference between debug and release
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105 Adkins
Refugio, TX 78377
About this property
Huge country home in Refugio County near the fairgrounds. Has a circular driveway in front of the property and also leading to the backyard to a storage building for the water well and a shop with built cabinets and a single garage door leading to the beautiful backyard full of oak trees. The home has 3 living areas, 3 nice size bedrooms, 2.5 baths, an office, and a formal dining room off from the kitchen. This home is ready for a big family to enjoy.
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http://www.corpuschristi-rentalhomes.com/showcase/105-adkins-refugio-tx-78377/10274-410338
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09/29/2009
Hoarders paradise
I recently went to a wonderful wedding at Voewood a beautiful Arts and Crafts house in Norfolk, it had such a magical feel about it. Full of collections and quirky objects, it's jam packed to the rafters with shells, paintings, vintage furniture, animal hides, retro glass and china, it was a treasure trove of found objects. The next day I took a walk on the beach at Holkham and it was stunning, so peaceful and serene. Norfolk, I'm hooked!
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I truly love white bed linens - I can happily layer sheets and duvets and comforters and blankets and pillows and keep the all white theme - I have had an all white bed for years . . .You can change accent colors, furniture styles, architectural features and the bed stays pristine. If a piece wears out you can replace it with another white piece - no going out to buy a whole new bedding set
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14846, Hunt, New York Weather This Week
14846, Hunt, New York weather forecasted for the next 10 days will have maximum temperature of 28°c / 83°f on Mon 02.
Min temperature will be 0°c / 32°f on Sat 07.
Most precipitation falling will be 2.09 mm / 0.08 inch on Sun 24.
Windiest day is expected to see wind of up to 34 kmph / 21 mph on Thu 05.
Visit 3 Hourly, Hourly and Historical section to get in-depth weather forecast information for 14846, Hunt, New York.
Which months receive most rainfall in Hunt (14846)?
If you would just like to know what the weather was for a past dates for research or education or you are just curious then visit our historical weather of Hunt (14846) section.
Hunt (14846) weather in September
Daytime temperature stays around 22°c and at night it goes to 11°c. In the month of September on average Hunt (14846) gets 83.63mm of rain and approximately 8 rainy days in the month. For the most part the humidity is around 79%.
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08 34:15:5909-26 12:12:2501 58:02:27 14:15:0302-04 50:35:2013 43:59:4001-11 33:13:34 58:22:1612-18 21:13:50 2016-10-30 32:37:35
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- After this brief overview of Jupyter Notebooks,
we will now start with the notebooks further.
Before we show you the great Python library is,
In [4]:
!tail -n 5$filename
all of that plotted nicely on a graph.
As I mentioned before we will learn more
about matplotlib in week five.
Next we will discuss the numpy library in Python.
That should be fun.
In [5]:
!grep -i "Unix"$filename
I would like to quickly overview how to use UNIX commands
to use UNIX shell commands,
and more interactive way to use UNIX commands.
like we execute them on a UNIX shell.
called UNIX in the same directory with this notebook,
you have a cold folder called .unix
So here we say filename ./unix/shakespeare.txt
To display this variable we can use the UNIX way
and use the echo command in UNIX
then we don't need the UNIX, like dollar sign.
for that UNIX variable resolution.
As you would remember in our UNIX exercises
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Ailbhe
Meaning and name origin
Ailbhe\a(i)-lb-he, ail-bhe\ as a girl's name is pronounced al-by, al-vy. It is of Irish and Gaelic origin, and the meaning of Ailbhe is "white". From albho. The name of a legendary female warrior and a miracle-working saint.
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Appearing lecturers of the United States offers precise, revealing interviews with 50 of the main influential modern American appearing individuals who provide an extraordinary glimpse into the realm of actor education within the usa.
A fascinating new perception into the Falklands clash, overlaying each element of its origins and the political and diplomatic reaction to the Argentinean motion in addition to illuminating bills of the army motion to retake the islands, at each point of command. In June 2002, precisely two decades after the cessation of hostilities among Britain and Argentina, a few of the key individuals got here jointly at an immense overseas convention.
Linda is as pretty as her sister (is). 17. The more exercise you take, the better you feel. 18. It's warmer today than it was yesterday. 19. Marian types as quickly as Linda (does). 20. She doesn't run as fast as her brother (does). 31 2000 bilingual phrases level 4 21. He spends more money than he earns. 22. They didn't play as well as we did. 23. This morning he looked happier than last night. 24. My husband spends more money than I earn. 25. They don't pay as much as we do. 26. You work much more than I do.
She sings louder than most singers. 8. Sweeping the streets is better than doing nothing. 9. Today it's darker than it was yesterday. 10. He does the ironing, which is better than watching TV. 11. Ill do it myself, which is better than calling a technician. 12. Doing things oneself is safer than letting the children do them. 13. It will be cheaper to buy a new car. 14. He didn't run as fast as we expected. 15. They work much harder than we did at their age. 16. Linda is as pretty as her sister (is).
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70 Over 70
Pineapple Street Studios
41 minutes 6 seconds
"Not Knowing Is a Gift" with Marty Linsky
Before 70 Over 70 goes on hiatus, Max sits down again with the person who inspired the show, his dad Marty, to talk about what he has learned from these conversations and what he hopes will stick with listeners.
Thank you to the more than 70 people over 70 who helped make this show possible:
Paul Price shares what he has learned about how to make the most of the time we have left. Then Max talks with Dr. Diane Meier, a geriatrician and founder of Mount Sinai's Center to Advance Palliative Care, about what she has learned from helping so many people make meaning of their lives, how to have hard conversations with people we care about, and why 70 feels exciting and unknown.
Special thanks to Agnes Frith and The Golden Wattle Cafe, "a regular cafe event for people living with dementia, their carers, and others who would like to join us."
Greg O'Brien shares how a terminal diagnosis revealed his purpose in life. Then Max talks with Judith Light about how her career opened up when she started to focus on what she could give rather than what she could get, and how that transformation has helped her think about death in a "real, conscious and alive way."This week we're going back to our first interview of 70 Over 70 with Sister Helen Prejean, who has dedicated her life to ending the death penalty in America. Sister Helen's interview helped set the tone for our show, and as 70 Over 70 comes to an end—yup, we've only got a few episodes left—we wanted to revisit this first conversation and share Sister Helen's thoughts on what it really means to be present, how to show up for others, and why gratitude is so important at any stage of lifeDiedre Wolownick tells the story of how she became the oldest woman to climb El Capitan in Yosemite National Park. Then Max talks with Twiggy about her career as an international supermodel, how she thinks about that time in her life now, and why getting older doesn't faze her.
--
If you want to hear more from Twiggy and her friends, check out her podcast, Tea with Twiggy.What You Earn Today Will Carry You on for the Rest of Your Life" with Lilly Ledbetter
Phyllis Irwin and Lillian Faderman share the story of how a legal loophole allowed them to create the life they had always dreamed of. Then Max talks with Lilly Ledbetter about the amazing story behind the Lilly Ledbetter Fair Pay Act, how a single moment in her 60s led her to become a prominent activist in her 70s and 80s and why her fight for equal pay is far from overonai Helu Thaman explains how teaching high school English deepened her appreciation for her native language. Then Max talks with David Crosby about why he feels incredibly lucky to still be alive at age 80 and how he's starting to plan for a future where he's no longer able to make musicrishnamurthy shares what it feels like to accept new limitations. Then Max talks with Russell Banks about why writing comes more easily now than ever before, how he learned to let go of the anger that drove him for so long, and what it really means to be aloneWe Are This Crazy and Magnificent Species" with Dr. Bessel Van Der Kolk
Sid and Miriam Moss explain why their 67 year-long marriage has been so successful. Then Max talks with Dr. Bessel Van Der Kolk about his life-long pursuit to understand the nature of trauma: how the pandemic has reshaped his definition of trauma, how he applies his experimental research to his own life and how we can make peace with our past at any ageJackie Batson shares why she hasn't given up hope on finding the man of her dreams. Then Max talks with actress Susan Lucci about what playing the same role for 41 years — Erica Kane on the soap opera All My Children — taught her about herself and about getting olderMichelle Drappi and Father Joe Carey share the story of their unlikely friendship. Then Max talks with Congressman Barney Frank about how the world has changed since he started in politics and how, after a career dedicated to helping others, he has learned to accept help in his own life today
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$1,896,944,109,232: Time to hit reset on student debt. All of it.Today in America, an entire generation is burdened with a lifetime of student debt that makes them less likely to buy a home, start a new business, or even start a family.
There are many thousands of young people who are graduating college with $50,000, $100,000, or more in debt and some of them, for financial reasons, weren't even able to finish their degree.
And if you go to graduate school or want to attend medical school, law school, or nursing school we're talking about young people who have assumed up to $400,000 or even $500,000 worth of debt.
Further, sadly, hundreds of thousands of working-class high school students no longer see college as an option because of their fear of leaving school with massive debt.
It is time to hit the reset button.
There is $1.8 trillion in student debt owed by more than 46 million Americans — a number that has tripled since 2008, and the overwhelming majority of which is owed to the federal government.
I am urging President Biden to do the right thing.
To cancel it.
All of it.
Because here is the truth:In the richest country in the history of the world, it is a national disgrace that we lead the world in the amount of student debt owed by our people.
In the richest country in the history of the world, hundreds of thousands of young people should not be giving up their dreams because paying off their student loans is too expensive.
In the richest country in the history of the world, we should understand that investing in our young people's education is investing in the future of our nation. It's not only good for the individual student, but for our entire economy.
No, that is not what America is supposed to be about.
We have adopted a very warped sense of priorities when we can bail out Wall Street for their criminal activity that crashed the economy, but we can't cancel student debt in this country.
We have adopted a warped sense of priorities when some of the wealthiest people and largest corporations in our country pay little or nothing in federal taxes, but we can't cancel student debt in this country.
We have adopted a very warped sense of priorities when we give billions of dollars to Jeff Bezos' space company, but we can't cancel student debt in this country.
We have adopted a warped sense of priorities when we can always find enough money for war and the military — even more than President Biden asked for — but we can't cancel student debt in this country
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As most people (particularly readers of this column) are aware, there are many disputed areas and issues around the world. Some are remnants of past colonialism, when boundaries weren't demarcated very accurately, especially in areas of difficult terrain — high mountains, deep jungles and so on. Some are the result of long-standing historical and cultural differences between two or more nationalities, where each is claiming a historical right to a piece of territory, a name or an island. And of course some occur due to the increasing tension over the scarcity of natural resources and the need to secure territory that might contain energy reserves or arable land or fisheries.
Regardless of the reason for the disputes, one often overlooked aspect of their existence is the tangible impact they have on the business world in the affected countries and beyond. The negative human cost is often all too clear, as is the military spending and political wrangling that continues to either perpetuate or resolve the disagreements. But beyond the geopolitical aspects of disputes, they have a real impact on people who may not even be directly aware of their existence, beyond being a persistent news item.
While I've referenced it before in another context, the example of the video game Age of Empires II: The Age of Kings is very applicable here. When this title was released in 1999, the standard cover of the game's packaging contained a depiction of three warriors from history: a Viking, an Anglo-Saxon and a Japanese Samurai. The intention was to use this same packaging artwork worldwide, but when the game was shipped to South Korea, the publisher quickly learned that some Korean retailers were reluctant to place the game on their shelves. Why might that be? Well, back in 1999, around the time of the game's release, Japan and Korea were experiencing a major falling out due to a flare up in tensions of the disputed islands of Dokdo/Takeshima in the middle of the Sea of Japan (or East Sea, from the Korean perspective). Dokdo is the Korean name, Takeshima is Japanese; the islands are historically known as the Liancourt Rocks.
Because of that periodic rise in geopolitical animosity, Korean consumers were avoiding all things Japanese, and out of respect for their customers, the retailers likewise wanted to avoid inflaming sensitivities in their stores. The game still sold in South Korea, but when the Age of Empires II expansion pack was released, the Korean packaging art prominently replaced the Aztec warrior seen in all other locales with a Korean general in front of two other historical soldiers, definitely making the packaging more appealing to Korean consumers.
Over the years, we've seen this form of retail retaliation take place in various markets, and it's understandable. Ordinary citizens in a specific locale who disagree with another country's actions really don't have a lot of leverage to make a difference, except when it comes to their spending habits. On more local levels we see this kind of business boycotting taking place on a regular basis, as it's a common part of citizen uprising to disagree with the actions of a specific business and then try to choke the flow of income to that business. What makes the phenomenon to which I'm referring more unique is that this happens on a national level. It's not just a few citizens boycotting over one company or one issue; it's an entire nation wanting to economically damage another nation in lieu of overt military action.
On the broader geopolitical scale, this isn't necessarily new. We've seen this tactic employed when the community of nations wants to send a strong message to a specific country, usually after traditional diplomacy has failed. These agreed-upon sanctions can take various forms, usually economic but sometimes also diplomatic (such as cutting off ties to a country), military (arms embargoes or limited military strikes) or even sports-related (such as not allowing participation in the Olympics or other global events). The economic sanctions are often most commonly employed, as it's meant to cause the target country some tangible pain in order to get it to succumb to a desired action, such as withdrawing from a territory or agreeing to a cease-fire. So this particular means of showing displeasure for another country is well known and typically used in the direst of circumstances to get the attention of the target locale.
Yet we have to remember that we live in a new world of instant community activism, empowered in part by growing social networks and rampant mobile technologies. So in the "old days" it could take weeks or months for such a response to gain momentum, but today we're talking about literally hours or just days. The impact is no less severe, and because of the swift reactions in response to things like geopolitical disputes, the impacts can in fact become even more swiftly pronounced.
Most recently we've been watching the intense unfolding of the island dispute between China and Japan. In the East China Sea, located to the southwest of Japan's island of Okinawa and to the northwest of Taiwan, lie a small group of islands known to Japan as the Senkaku Islands and known to China (and Taiwan) as the Diaoyu Islands. The sovereignty dispute over these uninhabited islands dates back a few centuries and both China and Japan have asserted historical evidence to try and bolster their claims. The current situation was framed in the post-World War II era when the United States withdrew from the islands and its occupation of Japan, and ceded the islands to Japan. Both China and Taiwan maintain claims to these islands but they've been under Japanese administration since 1972.
As is common with most island-based disputes, the issue was relatively benign until it was believed that the seabed around the islands contains a substantial petroleum and natural gas reserve. Given the United Nations Law of the Sea, any country that maintains sovereignty over even a tiny rock that remains above "mean sea level" is entitled to a 200 nautical mile "exclusive economic zone" around that feature, which means a potential bounty of not only energy resources but fisheries as well. That very tangible economic benefit is what drives the furor over the islands today. Taiwan has been all but diplomatically sidelined in the discussions, yet the tension between China and Japan has mounted steadily, and has reached concerning levels in 2012.
The negative relations between the two countries experienced a crescendo in September and October 2012 with widespread public protests in China and Japan (Figure 1). This wave of negative sentiment was evident not only from the expected diplomatic saber-rattling, but much more visibly in the business sector. Toyota reported that its September sales in China dropped a staggering 40% and Mazda's dropped 33% as the dispute became more heated. Nissan and Honda also indicated a drop in expected sales revenue from China, and all four Japanese manufacturers had to cut back on auto production. Were Chinese consumers simply not buying automobiles? Hardly, because sales of BMW jumped 55%, Volkswagen grew 20% and Korea's Hyundai increased by 15% in the same month. And the economic effects weren't limited only to cars; Japan-based All Nippon Airways saw massive cancellations of tickets on the Japan-China routes and Rohm Semiconductors had to reduce production because they supply parts to many Japanese auto manufacturers. Obviously this effect ripples onward from the affected companies to the affected workers and merchants relying on the workers' wages and spending habits.
Economic backlash is indeed one of the new forms of retribution in today's globalized business community. Some speculate that in the Senkaku/Diaoyu case, the Chinese response was carefully orchestrated from the central government in Beijing, and that may have been the case, but regardless of the driving factor, the end result remains the same.
Most typically, the responses to both geopolitical and cultural disputes are not so overt and extreme. For companies developing products and content for markets embroiled in such disputed issues, the challenge to remain as neutral as possible is clear. If one represents a company based in a country that is party to the dispute (such as a Japanese company), there's little you can do to avoid potential retribution because the crowd's activism won't discriminate against a "good" or "bad" company — it's purely about nationalism.
What needs to be most emphasized in this dynamic is the overarching need for businesses and content developers to be keenly aware of the state of sociopolitical events in their target markets. The ebb and tide of geopolitical reactions, nationalism and cultural dissonance are out of anyone's control; the only thing you can do is be knowledgeable and informed of the current situation. This also needs to be done in conjunction with an honest assessment of the culturalized condition of the company's content — is there anything in the content or even about the company itself that may serve as a trigger for local reactions, given the events at the time? In some cases, it can be wise to postpone a launch or concentrate on other target markets until the flare up over the dispute subsides (or hopefully, is resolved
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About th ...
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▼▶ the edge of your seat wondering where they may go next. Stayed tuned to keep your finger on the pulse of what people are already calling a road map to entertainment in The City!
To hear another side of Paul, come to one of his live shows to get that unfiltered perspective look at his topsy turvey life as it unravels in front of your eyes. Paul can work relatively clean, but is best known for his unique style of blue comedy. National touring comedian with his roots in the San Francisco Bay Area playing such legendary clubs at The San Jose Improv, The San Francisco Punch Line, The Purple Onion, The Hollywood Comedy Store, Tommy T's, plus many more.
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https://www.gigmasters.com/standupcomedian/paulbrumbaugh
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6 entries have been written about this.
I took a break from Grisham for a while when his books became a bit boring. Came back for "The Last Juror" and decided to keep going. This book wasn't horrible, but it could have been better. Do I recommend it? Yes, if only because I REALLY want to go to Bologna on vacation now. Sounds divine.
as many of the other thrillers I've read. It slows down too much and focuses on the duller parts of the character's daily life in Bologna. The beginning and end weren't too bad. Would have appreciated a little more action and suspense thrown in, though. Even corny action/suspense. However, I loved the Italian in it – picked up a bit and now I want to learn it, too.
February 2005 – Hardback book. I bought this a while back at Costco but I haven't been reading "paper books" lately. I finally started it last night, though I only read about 3 pages. I just need to tear myself away from the computer long enough to get sucked in…
As usual, Grisham writes a page turner. I chewed up large chunks of this one in a relatively short amount of time. That said, this is not his usual legal thriller. Grisham seems to want to try and just write a thriller and, for the most part, it's not that successful. There are long stretches of the novel where next to no action occurs and the plot doesn't move foward. It reads almost like a travel guide to Bologna, Italy for large sections of the middle of the story as Joel learns about the culture and people. And the suspense sequences aren't quite that suspenseful as there's never any impending doom facing Joel as in other cloak and dagger type thrillers.
A good try, John, but not a successful one. You've branched out before with A Time to Kill and A Painted House, both of which are far better novels than this one.
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601607b0-0ea2-41db-9781-93a072d21fca
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http://www.allconsuming.net/item/view/10496
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24 August 2023
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The 7th edition of Solarplaza Summit Italy was a great success, bringing together over 200 attendees and featuring more than 25 expert speakers. The event kicked off with a vibrant pre-conference networking dinner, setting the stage for a day of insightful discussions. Download this report to get a detailed overview of the event Italy. Be the first to know when the new edition will be held by signing up for updates.
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https://www.solarplaza.com/resource/12864/post-show-report-solarplaza-summit-italy-2023/
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Abstract
This study was carried out within the pilot project ordered by the Ministry of Education for the government to decide if the children should start school from the age of 6 or 7 years. The study results prove that the physical development of children at this age is greatly variable, the dispersion in all the parameters is very great. Thus, we can conclude that one should decide of starting school at the age of 6 years individually by the child's parents jointly with the family doctor. On average the physical development parameters correspond to the norm, though a part of children are lagging behind their peers. The growth and development at the age of six and seven years is different and individual, there is no pronounced gender dimorphism.
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http://ojs.utlib.ee/index.php/PoA/article/view/poa.2013.22.27
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3 Simple Steps for Fireplace Safety
Gas-fueled fireplaces are becoming more common in homes across America. With that warmth, some gas fireplaces installed before January 1, 2015, come with a risk of burn. Having no warning labels or a barrier to prevent touching the glass.
To minimize the chance of burns from hot glass, follow these safety tips:
The gas fireplace is a convenient and easy way to warm up any room of your house without having to turn on the homes heating system. This saves money on your heating bill by adding warmth where you need and when you need it.
Supervise children never leave children or pets unattended near an operating gas fireplace or one that has recently been turned off. The glass on a gas fireplace can take an hour or more to cool down.
Keep the remote control out of reach of children. The HBPA also recommends having a gas fireplace specialist install a switch lock to prevent children from accidentally turning it on.
Always wait for the appliance and glass to cool down before getting too close to it. Some gas fireplaces and inserts are regulated by a thermostat turning it on and off automatically. Always assume the glass is hot.
According to the HPBA (Hearth, Patio & Barbecue Association) recently reported that 61% of people in the united states own a fireplace and 37% of those are fueled by gas. 14% of homeowners own a gas insert heating appliance.
Gas fireplaces manufactured after and installed after January 1, 2015, are required to have a barrier if the glass temperature exceeds 172 degrees Fahrenheit. It is important to inform everyone in the home or visiting on how to be safe around your gas fireplace.
Download the printable fireplace safety tip sheet for use in your home, office or rental property
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9527df5a-981f-4beb-b75c-8617ee841112
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https://www.nicehomeservices.com/blog/3-simple-steps-for-fireplace-safety/
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07.03.15
One of my guiltiest pleasures happens to be drinking my meals - hey, don't judge, I just like the way it makes me feels!! That said, I must admit - my Brunch in a Cup is a most fabulous fit! What's not to love about veggies, shrimp + fancy pickled things - swimming in vodka, v8 and every sauce in between?! I truly cannot possibly think of a better way - to fuel and sauce up for the day! So the next time you find yourself in need of a little 'pick-me-up' - you really ought to try my Brunch in a Cup!
Forgive my absence yesterday, for here's the full disclosure - I was keeping company with none other than Mrs. Hangover!!
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http://www.flmgo.co/blog/2015/7/2/cotm-bloody-brunch-in-a-cup
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https://konsensus.se/255-online-pay-day-loans-same-go-out-zero-credit-2/
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Absolutely the worst car rental company, I have seen so far. We went in there and were ushered to use a Kiosk. The kiosk goes all the way until you go the option of buying additional option. If you select, no additional insurance, it asks to go back to the desk. The whole 15 mins process after a long flight was terrible.
The person at the desk was rude. He again tried to sell us insurance telling us terrible catalyst converter theft happening in London. I had a California and a UK driving license. I scanned the UK one on kiosk. He said that I cannot use it since I am not a native in UK anymore and cannot switched to California driving license as I had already scanned it. Refused to give me car.
I would suggest everyone to be think twice and think again before using Easirent. I ended up renting for a reputable international car hire company for almost the same price but with much better customer service.Dear Team,
Having recently used Easy Rent Cars I felt it necessary to get in touch and write reviews (which is a first for me) of our very bad initial experience with your supplier 'Easirent'.
My wife and I recently arrived in Stansted Airport, London where we had reserved a hire a car with yourselves, which involves calling a number to get on your shuttle bus outside the airport which then takes customers to your car garage nearby. Once reaching the bus stop area outside (where we were told to get on the bus), we saw the bus and waived it down, the bus driver rolled his window down and said he "was full". As he drove past us to our utter bemusement my wife and I noticed he had several vacant seats.
I then decided to call the number again for pick up and the gentlemen said there is only one driver and he will do a round trip which will take 20 minutes. After waiting outside in the cold for 20 minutes the bus arrives again with the same driver 'Tanase' where we finally got on and asked him why he didn't let us on and say he was full when he had empty seats, he simply replied "I speak no English"! To say this was a lame excuse and the guy was totally rude and unprofessional is a huge understatement.
With the visit to the UK for a family funeral the next day and after a 7 hour flight this bizarre attitude was the last thing we needed.
When we arrived I mentioned what had just happened to one of the staff that was serving me at the desk, who apologised on his behalf and gave me an upgrade. I was not looking for an apology nor an upgrade, just simply relaying this on, as the whole experience was surreal and I'm sure if this happened to us, it's happening to other customers too that Tanase is supposedly meant to be picking up.
Please ensure this gets feedback to Management, especially in your Stansted Airport, London branch.
Regards,
"If I had been on a tight schedule I would have been upset at the delay at pick-up"
About Easirent:8.0/10
It took about an hour a half to receive the car there was a backlog of customers at the facility at Heathrow. The car trip meter was not put to zero but I only realised this after I had set off in the car.
I had 2 people with limited mobility travelling with me. The car was supposed to be ready from 3pm, and it was 4.50pm when it was ready. 10 minutes for it to be ready became 1 hour. Car was waiting to be cleaned, while other cars that were not waiting for rental were being cleaned. Staff had no interest in expediting the cleaning of the car until I eventually lost my patience. A very bad customer service
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https://www.qeeq.com/car-rental-reviews/supplier-72-city-3243?page=2
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airport, but we would have loved to stay much longer. It felt like the very heart of Ireland. We're so grateful!
Kathryn2016Tipo de habitación
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Capacidad
Dormitorios was a lovely host! She has taken so much care in renovating her lovely B&B. The town was delightful and breakfast was delicious!
Bruff is a charming town in the countryside and Miriam's place fits in great. It was a pleasant stop over outside of the hustle and bustle of the tourist areas.
Serena2015-07-24T00:00:00Z
The accommodation was first class and Miriam was a wonderful host, very welcoming and great with suggestions. We used this place as a base for us to see the area - overall a wonderful experience! Thank you Miriam!
Vince2015-07-06Nice BandB with many features of a hotel.
Sarah2016-12-31T00:00:00Z
Miriam has got to be one of the most amazing hosts I've had the pleasure of staying with hugeCapacidad
DormitoriosSituated on the N69 Coast Road between Limerick and Listowel/Tralee, 8 miles from Limerick City, 22 miles from Shannon Airport and 5 miles from Adare Village, Slattery's Bed and Breakfast is a charming village Guesthouse with a walled garden and guest sitting room. Next door to the B&B is Slattery's Pub, which is famous for its music and friendly atmosphere and has been owned by the Slattery family for over 150 years.
Kildimo is ideally situated for day trips to Killarney, Ballybunion, Blarney, Cliffs of Moher, the Burren and the Rock of Cashel. The sportsman has an excellent choice of activities in and around Kildimo, including coarse and sea angling, golfing, equestrian facilities and hiking. The River Maigue which runs past the village is popular for trout and salmon, while nearby Bleach Lough offers great trout and pike fishing.
There's horse racing just 5 miles away at the Limerick racecourse in Patrickswell and Thomond Park, spiritual home of Munster Rugby is just an 8 mile drive into Limerick city.
Kay was a great host. Flight got changed to next day and she gladly moved it to the next day without any questions. Accommodations nice and morning breakfast plentiful. She also suggested sites to visit and routes to drive.
Terry2015-09-23T00:00:00Z
I stayed at this B&B in Kildimo. My experience there was wonderful. I really enjoyed the spacious room. The breakfast was Great!!. The host made me feel welcome and provided a lot of assistance with visiting the local area. I highly recommend this place!
Gerald2016-06-08T00:00:00Z
Slattery's was great-- an authentic BnB experience without the stress of having to figure things out on the spot. A very nice New Zealand family stayed while I was there and Kay helped them to sort out some car trouble AND find their next accommodation. The room itself was quite tidy and clearly intended for two people, which was a nice surprise for a lone traveler like myself. In the morning, Kay fixed an exquisite breakfast. My only regret is that I could not finish it!
Samuel2015-09-08T00:00:00Z
Great place and great value for money, huuuuuge bed too! Kay took some time to chat with us which always more pleasant than just giving the key and breakfast time and that's it. A really good place!
Clement2016-08-15T00:00:00Z
This place is like stepping back in time! I feel like I could have written a novel here alongside Joyce! The shower pressure was great and the WiFi faster than I expected. Kay is a great cook and it was a quiet place to stay.
Danielle2016-06-17T00:00:00Z
This was in a great location, the building is 150 years old. There are some issues that need addressed. The room we had was dusty, and musty with mold in the bathroom. There is a street light right outside the front of the building and the building is right on a major road. This was easy to find with a pub next door and the irish breakfast was great. She was interesting to chat with, and a lovely host. She gave good directions to a nearby pub that served food.
Vicki2016-09-01T00:00:00Z
Unfortunately after accepting the reservation the booking fell through, so I cant comment on the facilities at Slatterys pub and guest house. They did seem to be exactly what I wanted tho I would recommend messaging this host before paying for your accommodation, if you are arriving the same day2014-07-19T00:00:00Z2015-09-24T00:00:00Z
Evelyn had a wonderful home to host us and was very attentive and accommodating. Many thanks for a lovely stay!
Mark2015-06-06T00:00:00Z
The description was accurate. Better than we expected
belinda2014-07-27T00:00:00Z
Evelyn was very helpful and attentive. I enjoyed staying here with my 5 children. Breakfast each morning was excellent. No complaints.
Richard2013-06-14T00:00:00Z
Beautiful home and very clean. Neighborhood was very upscale. The host was above and beyond helpful.
susan2015-06-28T00:00:00Z
Evelyn was a great host. We had a very nice breakfast and enjoyed her company.
Earllaine2015-07-31T00:00:00ZTipo de propiedad
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Dormitorios spotTipo de propiedad
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Dormitorios
This room is in AvondoyleB&B & is an upstairs family room -photos can be seen in main Avondoyle listing. This room has 1 Double & 2 Single Beds) sleeping max 4 people with private bathroom.**Price: €60 min 2 adults, additional adults €25 per person**
Evelyn is an experienced and kind hostess and she has an excellent home. She was helpful and friendly. She cooks the best breakfasts we've had in Ireland. The house was well equipped and very open and comfortable. She was always providing us with little extras.
Derek2016-07-30T00:00:00Z
She is the nicest lady and she treated us just like we were her kids. Evelyn was a great host and I 100% recommend staying with her!
Weston2016-10-09T00:00:00Z
Fantastic experience! Accomodation was excellent, our host (Evelyn) was really nice and very helpful and her home-cooked breakfast was delicious. Highly recommended! :-)
Silvia2015-06-21T00:00:00Z
we had a great stay many thanks the breakfast was brilliant and the scones were incredible great value ..thank you we will be back again
Mark2015-12-13T00:00:00Z
Very close to Limerick and easy to find.
Ian2016-08-19T00:00:00Z
Evelyn was so kind and talkable. We love to stay in her apartment, it was clean and cool. We also like the amazing Irish breakfast. Perfect host!
Valerio2016-08-05T00:00:00Z
Very comfy and clean bedroom. Very good breakfast We had the fruit plate.
Sandrine2016-08-12T00:00:00Z
When we travelled in Ireland, all our hostesses were very pleasant and welcoming except Evelyn. She was the ruddest person we have met in Ireland. From the moment we arriwed, she was displeased with everything. She was very unhappy that we arrived late, even though we phoned ahead twice. During breakfast, when we asked for eggs and bacon and also fruit, we were told that "it's not a four course dinner", and we are allowed only one items from the menu. It would be nice if such rules were explained to us earlier, since in all other bed and breakfastes we had a buffet style breakfast. She gave us one plate of fruit at the end with more rude remarks. Needless to say, we were not very happy and left as soon as we could. On the plus side, the place was nice overall. AndTipo de propiedad
Capacidad
Dormitorios
This room is in Avondoyle B&B and is an upstairs family room -photos can be seen in main Avondoyle listing. This room has 1 Double & 1 Single Bed) sleeping 3 people with ensuite bathroom.**Price: €60 min 2 adults, additional adults €25 per person**
Host double booked and took us to alternative accommodation, overpriced.
Patrick2016-09-17T00:00:00Z
Avondoyle was the perfect place for us, and Evelyn was the perfect hostess. I contacted her at the last minute for accommodation that same day, and she replied right away. She helped us with good local recommendations and treated my son and me like family. The house is gorgeous, peaceful, very comfortable, and is even better than the photos portray. She offers many choices for breakfast, all delicious. I would love to stay here again, and recommend anyone going to or near Limerick to do the same.
Allison2015-08-04T00:00:00Z
It was a great time by Evelyn. The most enthusiastic was our daughter. She didn't want to leave. She found it very nice especially the breakfast, the best we have had in Ireland.
Petra2015-08-01T00:00:00Z
We spent the weekend at Avondoyle. If you have a car is handy to go everywhere. In our case to Limerick and Bunratty. Evelyn is friendly and helpful, and her dog is cute. The room was clean, comfortable, spacious, and had all we need. Her Breakfast is delicious. Her B&B has a wonderful decoration and a beautiful view from her garden with orchards with the most sweetest apples. We love it!
Thais2016-09-25T00:00:00Z
Evelyn was very friendly and welcoming. She was very eager to help. The rooms were clean, comfortable, and had all the amenities one would need. Breakfast was spectacular. It was by far the best night during our stay in Ireland.
Michelle2016-05-30T00:00:00Z
Evelyn is a great host and the accommodation was good too. We got a really good rooms at a short notice and the breakfast was excellent.
Amit2016-03-28T00:00:00Z
The room was comfortable and as advertised; enough room for two. Evelyn offered us options from a perpared breakfast menu and the food tasted delisious. Evelyn was friendly and very helpful :) Great stay!
Irene2016-09-08T00:00:00Z
Had a great stay with Evelyn. My friend and I booked last minute and she was very accommodating for us and my 2 dogs. Quiet area and easy access for stopping on the way through Limerick.
Isabelle2014 place because of the outdoors space, the comfy bed, and the light. My place is good for couples, solo adventurers, business travellers, families (with kids), big groups, and furry friends (pets).
Wonderful place, comfortable bed, great breakfast, very welcoming, very accommodating! Just down the road if you need a bite to eat, Morrison's is great!
Suzie in AvondoyleB&B & is a downstairs family room -photos can be seen in main Avondoyle listing. This room has 1 Double & 1 Single Bed) sleeping max3 people with private bathroom.**Price: €60 min 2 adults, additional adults €25 per person**
A beautiful place just outside of Limerick, Evelyn was a great host, greeting us with tea and scones. Very peaceful at night, and only a few minutes into town. Very recommended.
Chloe and David2014-09-28T00:00:00Z
Evelyn's welcoming personality and kindness are unmatched- from the moment you step in through the doorway, she's offering hot teas and making you feel right at home. The house is in a quiet location with a spacious backyard, and a great seating areas to lounge and relax. Evelyn has done a great job maintaining the space to be accommodating and comfortable for all guests, yet still makes the house uniquely her space through decorations. The dog Holly is a total sweetheart too and cheers you up through your stay, even when the weather is overcast.
Kirklann2016-06-27T00:00:00Z
A beautiful home in an ideal location hosted by a warm, friendly inkeeper.
Great house and great location! Bernie was accommodating even helping us to re-heat food the night we arrived.
Mary2016-03-08T00:00:00Z
My sister and I stayed here for one night. We arrived at the Castleview B&B little later than we wanted to but Bernie, our host, was very kind and greeted us warmly at the door. She put us together a nice breakfast (warm croissant + homemade jam) and coffee the next morning and made us feel like we were at home. Perfect stay if you need a place to relax on your roadtrip.
Wonderful spot. Bernie was very hospitable and helpful. The room was lovely and the location was perfect. I would recommend this place to anyone.
Jamie And Christi2016-09-23T00:00:00Z
Beautiful home in a peaceful location just a few km from the city. Each bedroom had its own bath. Common spaces are shared in part with the friendly host family, but we had our own large parlor with HDTV. The morning breakfast was delicious and filling, with a wide assortment of hot and cold foods. Bernie was very kind and helped us with veg-friendly restaurant recommendations.
Matthew2016-09-11T00:00:00Z
I highly recommend Bernie's B&B. She's a wonderful host. Her place is spotless and parking is excellent. I would recommend you stay more than one day in Limerick.
Ben2016-10-09T00:00:00Z
Amazing stay, both the house and the owner were lovely. Thanks to that we could learn more incredible country. Thanks for everything!
Dann2016-09-26T00:00:00Z
Bernie was amazing, the room was great and she was super nice and even gave me a ride into the city. The breakfast was also great and when I was leaving she drove me to the University herself. I would highly recommend staying here to everybody. The cab I took to get there from Limerick bus station only took about 10 minutes so it's really close.
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https://www.airbnb.es/s/Croom--Irlanda?type=bnb
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5 Automotive Extras for a Comfortable Ride
Nowadays, we aren't just interested in reaching our destinations, we want to do so in style and comfort. It's no wonder that the newest cars are largely marketed based on their interiors. Of course, an attractive exterior is nice, but it's what we experience from the moment we open the car doors that matters most to us. If you spend a lot of time in your car, and who doesn't these days, should you look at adding a few extra features? There are some fun and interesting features you can add to the ones your car's designers already included.
1. High Ground Clearance? Make Getting in and Out Easier
High ground clearance is a must if you're inclined to drive on rough roads. For city driving, it's a luxury that lets you tower above the traffic. But getting in and out could be easier. The best running boards solve the problem. The coolest ones even retract under your car as soon as the door is closed, sliding out again when you open them. It's a nifty trick that's bound to impress, and having that leg up when getting in and out of your car will be a help. Of course, there are also simpler versions of the running board, but this idea is a winner!
2. Never Burn Your Hands on a Hot Steering Wheel Again
When the sun is beating down on your car, its interior heats up fast! As for your (usually black) steering wheel, it gets almost too hot to handle. If these "ouch" moments get you down, there's a simple solution, and it's cheap too. Simply get a steering wheel cover with a cooling gel inside it and put an end to those hot hands moments!
3. Because One Must Mention it: The Echo Auto
If you need entertainment or directions on long roads, fiddling with phones and touch screens is a no-no unless you pull off. But you can bring Alexa to your car with the unsurprisingly popular Echo Auto. It's not exactly cheap, but it does add that touch of convenience. Google information on the sights you see, play the music you like – all without taking your hands off the wheel.
4. An Extra-Wide Rear View Mirror
Clip on an extra wide rearview mirror for improved visibility. Getting that wide angle is a big plus, but don't forget to check your blind spots anyway. All the same, you'll feel more comfortable when you can watch your back (and a bit of the verge too) through your extra-wide mirror. And it's such a cheap extra, that there's no real reason not to add it to your wishlist.
5. An Odor-Free Air Purifier
The smell of ordinary car deodorizers can be overpowering. Most of them simply cover the odor and don't actually remove it, but a real air purifier that plugs into your lighter socket actually scrubs the air while you're driving, removing all those nasty smells permanently. It's just the thing for keeping a cramped space smelling fresh.
There's so Much More
Looking through lists of motoring accessories is always entertaining – and you might find a few gems you absolutely want. From simple extras to high-tech add-ons, there are tons of ways to make your ride more comfortable, convenient and enjoyable without breaking the bank. Buying your first car? Celebrate by spoiling yourself to a nifty extra and be sure to show it off
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https://thefieldsofgreen.com/5-automotive-extras-for-a-comfortable-ride/
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https://airbeeusa.com/2022/10/01/100-free-slots-real-time-broker-and-you-action-bank-slot-can-desk-online-game-at-the-streams-casino4fun/
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87 W Columbia Avenue
Fort Mohave, AZ86426
Explore This Property
Single Family Detached
-
New 3 BR 2 BT 4 Car Garage Home in the new Fairway Village Estates. Independence Model with wrap around patio. Stunning Builder Value Package of upgrades included in home; block wall, front yard landscaping, wrought iron fencing, granite/hard surface countertops, upgraded cabinetry, and much more. (See attachment) Club house with pool included in next phase, no HOA fees until then. Still time to pick colors and countertops7 W Columbia Avenue, Fort Mohave, AZ
86426
is currently for sale.
6087 W Columbia Avenue, Fort Mohave is listed
for $307,900.
This property has 3 bedrooms, 2 full bathrooms, and approximately 1,829 square feet.
If the property located at 6087 W Columbia Avenue, Fort Mohave, AZ isn't what you're looking for,
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021264ef-9537-42e8-b07a-149f4ae0046b
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https://www.century21.com/property/6087-w-columbia-avenue-fort-mohave-az-86426-REN029900421
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Best anti virus?
hi. I was wondering what is the best FREE anti virus for windows 7. Currently i have Avast, which seems to be doing a good job. I was wondering if there was a better on. Also how does Microsoft security essentials rank? Is it one of the best?
I like Microsoft Security Essentials, although it recently failed an AV test (can't remember which). Avast is my second choice. Stay away from AVG. Since you are already using Avast I recommend to just keep using it.
Remember with free, you often do not get the same features and issue corrections that you would get with a paid option. I would recommend thinking of buying a a program to get the best protection possible.
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http://www.tomshardware.com/forum/65321-63-best-anti-virus
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#1 - Would it kill lthem to put in a tutorial? I was very close to just chucking this game in at the start.
##3 - An "are you sure?" dialogue box if you end a turn with move left. So far I've died because (a) my son hit spacebar a lot; and (b) I hit spacebar a few times to turn off the screensaver.
That said, it looks like I'm becoming hooked on this game. Assuming my son doesn't take to pressing spacebar every chance he gets.
AturuxoAturuxo
Wanderer
iiago: #That's already implemented, you can use recipes you already know and have ingredients for to craft; i don't quite remember the mechanic but i'm pretty sure it's there.
Don't give up, it's a quite good game and it gets better once you learn a few nasty/profitable tricks ;)
Post edited October 04, 2016 by Aturuxo? Which I suppose shows why they need a tutorial! I will hunt that down - it will make life much easier.
I'm about 20hrs in now, so I guess it's safe to say that despite these quirks, I'm hooked :-)
dcfedordcfedor
Founder, Blue Bottle Games, LLC
d iiago! Thanks for the purchase, and I apologize for the usability issues. I definitely made more than a few mistakes on NEO Scavenger, though UI is probably one of the bigger ones.
Regarding the tutorial, Which aspect of the game do you feel you needed the most guidance with? My initial instinct was to keep the tutorial as light as possible, with just a few hints in the opening encounter (e.g. how to scavenge, walk the map, etc.). I was afraid too much tutorial would bore new players who were on the fence. But perhaps I need to dial it up a bit more?
As Aturuxo says, there is a "Quick Recipe" UI in the crafting screen. It's a tab over the ingredients that lets you see all known recipes. You'll start with a basic set that matches your chosen skills, and any recipe scraps you "hold" in your hand become learned, and any recipe you complete will also become learned.
As for "transfer all," this was indeed a popular request by players who spent more time in the game. I'll definitely be keeping this in mind for sequels, but for now, the closest available is "empty out" or the "take/drop" cursor mode (which just makes item transfers faster than "drag/drop" mode).
Regarding "are you sure" dialogs, I tend to be against these as they get in the way of smooth gaming. But I totally understand the need in some situations (as with children, cats, and other critters within reach of the controls). Perhaps this is something I'll have to consider as an option to be toggled in future games.
In any case, I appreciate the feedback, and I'm glad to hear you're finding the game fun despite its rough edges! - ok, I did not expect the developer to read this, much less respond. If I had known I would have been a bit more polite with my comments. Like I said, really enjoying your work.
With a tutorial, I suppose the thing that stumped me was understanding the opening interface. I assumed that the first picture I was looking at (inside the cryo facility) was the game screen. So I started off clicking on the cryo tanks etc to examine them, and the door to leave. Maybe I was in a bad mood at the time, but that drove me nuts.
So simple arrows that appear on the screen explaining "This is a picture of where you are", "these are your available actions" would have been helpful. An arrow explaining crafting would have helped the "quick recipe" UI, I saw the list of "known recipes" but didn't realise that I could click on them. An explanation of how to add to the known recipes would probably be useful too (although I figured that one out).
On the "are you sure" dialogues, totally understand the design choice. Although if you did put a few in, I suggest one if the player leaves behind a vehicle following combat. I have lost more than one load of goods that way.
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https://www.gog.com/forum/neo_scavenger/things_that_annoy_me_3hrs_in
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Acid Base Case Study
120 Downloads
Compressed Zip File
Be sure that you have an application to open this file type before downloading and/or purchasing. How to unzip files.
2.88 MB | 5 (student and teacher pages) pages
PRODUCT DESCRIPTION
This case study gives students the opportunity to see how the pH scale is directly tied to the respiratory system and how imbalances affect a person's health. This assignment would apply to biology, anatomy and physiology, chemistry, and health science classes.
•An answer key is included.
•Students will read a narrative about acids and bases and the respiratory system then look at three short cases about hyperventilation, diabetics and oil of wintergreen overdoes.
•Students will then answer questions about acids and bases based on the cases.
•Questions are presented in two ways which will allow you to have a class set or have students complete the questions within the case study.
•Case study can be modified to accommodate different academic
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d58659ed-4a3a-460f-80e7-273c207e223c
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https://www.teacherspayteachers.com/Product/Acid-Base-Case-Study-2555732
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Archive for the 'Revenge' Category
A rich businessman brings his mistress to a desolate hideaway in the desert. He's there for an annual hunting trip with two of his associates, who arrive a bit too early and get to know the girl as well. There's a pool party, a lot of alcohol and the next day, the girl gets violated by one of the buddies. Once the businessman finds out, he defends his friends and pushes her off a cliff, where she gets impaled on a pointy tree branch.
However, the girl isn't dead and she's out for revenge.
And this is the moment where the real movie experience starts. The girl survives a deadly fall, being impaled, being shot at several times etc… She manages to survive in the desert, fix her wounds, run around with a heavy machine gun, aim a riffle successfully, etc… Every setback makes her stronger.
Nothing is logical in this movie. But that's not the point. It's a visually and auditive stunning neo-cult classic. There's only four actors (well, five if you count the helicopter pilot) and there are only a few settings. It must have been a low-budget production, but the camerawork is excellent. The action is non stop and entertaining. The gore is abundant. And there's nakedness! Not by the female protagonist, but by the rich businessman who spends the last 15 minutes of the movie running around in the nude.
That character is played by Kevin Janssens, a Flemish actor who's a bit of a local celebrity, appearing in the gossip magazines for this affairs with other local celebrities. BUT, he's actually a fine actor and he chooses his roles cleverly. He could have gone for the commercial mainstream parts, but he does a lot of these weird indie things. And he does it well.
The movie didn't get a local release though. It didn't get a wide release at all. But it's available on iTunes and highly recommended. Unless you can't stand bloodshed and want a logical story. Then this is not for you. But try it, you may be impressed by the cool cinematographyAnother weird movie from the guy that brought us The Lobster. It's so weird, it's cool. It unsettling. It's funny. It's thrilling at times. It's a visual treat. The story is again not that strong. (A heart specialist gets jinxed by the kid of a former, deceased patient of his. Now his family has to suffer as well.) But that doesn't matter. It has a very remarkable opening shot. Go see it. It's creepy. It sets the tone right. This is Francois Ozon meets Michael Haneke meets Ulrich Seidl. Colin Farell is great at these kind of roles. He's really the only actor you can imagine playing this part. Nicole Kidman is also doing well. Even though she does all kinds of things you don't want her to do really. (Get naked, play dead, smoke, hit children,…) There's that scene where she jerks off a guy to get information. She does it so well. It makes you wonder whatever she did with Harvey Weinstein to get where she is now. Nevertheless. Great acting. Raffey Cassidy is one to watch out for as well. And that Barry Keogh kid kills it! Just go see it and then feel like WTF.
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A young girl needs to go live with her dad while her mother goes away on a longer holiday with her new boyfriend. The dad works at a slaughterhouse and has a tough time making ends meet. He lives in an apartment, where pets are not allowed. So when his daughter moves in with her dog tensions rise. At one point the dog is abandoned and left at its own devices in the Hungarian capital. He soon finds some fellow street dogs to hang with and try to survive. But when he's taken to an asylum during a dog razzia, things change. Because of all the following misfortune, he turns into an evil dog looking for revenge. And his former loving caretaker cannot save him.
This is one depressing animal misery movie. There's only some action and horror at the end. Once the dog is out for revenge, he's a killer machine. It would have been much cooler and interesting if this really was a revenge movie in the likes of Planet Of The Apes. Now it's more about a girl who feels abandoned by her mother and needs to adapt to a new situation (living with her dad). The fact that the dog gets abandoned and needs to adapt to a new situation (living on the street, in the asylum, with a trainer who preps him for dog fights…) doesn't make the movie any more interesting.
Yes, it's good to see a movie like this with real dogs and no computer animation. Yes, it's pretty amazing to see all these dogs run through the almost empty streets of Budapest. Yes, it's fascinating to see the dog perform really well (they used two). But in the end, there are only a few scenes where it looks fascinating. For the most part, the story just sucks.
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There's something really disturbing about this movie that is difficult to digest if you have given up on religion as something good. It's constantly referring to it, in particular the christian faith. The bible and christianity have both been used by slave owners and slave/civil rights resistance leaders as a source for their cause. That's a known fact. But in this tale, there's just too much focus on it.
Sure, it's the core of the story: a young slave learns to read the bible and then is later used to preach the bible to rebellious slaves so they can obey their masters again. At one point the man is ordered to preach a verse that goes like this: "Slaves, be subject to your masters with all respect, not only to the good and gentle, but also to the unjust. For this is a gracious thing, when, mindful of God, one endures sorrows while suffering unjustly." (Peter 2:18-19). That's in the bible! And however you interpret it or put it in a historical context, it's VILE.
Then of course things go wrong, at which point a fellow slave asks with reason: "Where is God now?"
Birth Of A Nation is the story of this preaching slave who uses his faith and skills to start a slave rebellion after having seen too much unchristian misery. It's based on true facts. The man did exist and he did transform from an obedient slave to a wrathful revenge rebel. So no critique there. It's wel directed and well acted by Nate Parker. (and other members in the cast). Yet somehow it's not as engaging as it should be. And that's not because there are hardly any 'good' white people on screen. It's just focusing so damn much on religion that you feel like the director wants people to believe faith is something good and will guide you through vengeance.
Revenge can be cool. Ask Quentin Tarantino. But revenge out of faith is just annoying and disturbing. But that's probably the whole point of the movie.
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The trailer promises a total different kind of movie, but Nocturnal Animals is still worth the watch. Just don't expect a classic thriller. It's very stylish. After all, it's Tom Ford who directed it. And it has the ever excellent Amy Adams in the lead role. She's an art curator who's not in a very happy place when the movie starts. Her husband is cheating on her and she doesn't get any satisfaction from her job. Her state of mind doesn't improve when she receives a novel written by her ex husband…
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Elle is a French comedy thriller directed by Paul Verhoeven and starring Isabelle Huppert and it's exactly what you think it will be. It's very French, it's very Verhoeven en it's very Huppert. It's La Pianiste meets Basic Instinct set in bourgeois Paris.
It surprisingly won two Golden Globes last night, so why longer postpone watching it? It's been out on dvd for quite some time now and Moonlight or La La Land are only released end of January over here in Europe.
It's fun! It's unique! It's hilarious at times, absurd at other moments, but most of all very subversive. The story fucks with your mind in the most perverted way.
A woman gets raped repeatedly and doesn't want to report it to the police. From the very first scenes it's clear this isn't going to be anything like other rape victim stories. On the contrary. It's very clear that this woman seems to get a kick out of being raped. And she has her own way of taking revenge.
It's a really cool movie. Isabelle Huppert is amazing and her character is fascinating. Verhoeven is taking the 'crazy protagonist' to a totally different level, which hasn't been explored that much or not at all. The humor is pitch black and works perfectly. The thrills are a bit of a disappointment and stop being relevant to the story after a while. However, the way Verhoeven introduces the possible attackers is clever: it can be almost anyone from the most obvious colleague who hates her guts to the least likely sweet ex husband… Hey the movie gets that perverted that you start thinking she got raped by her son! Yeah. That's how fucked up your brain starts to work.
But in the end. It's entertainment. It's how Tarantino would make movies if he had grown up in Europe.
Does it deserve the two Golden Globes? Well… it deserves the extra attention it can get.
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https://trailertherapy.wordpress.com/category/1-genre/thriller/revenge/
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1808 mohegan trail Block Island, RI 02807
Presented By
With sweeping views from Montauk to the country's first off shore wind farm, this magnificent new construction home will take your breath away. This thoughtfully designed and built home has everything you need. Offering four bedrooms, three and a half baths, three living areas and a covered dining porch as well as a lovely sun porch that takes advantage of the gorgeous views. The ensuite master bedroom opens to the covered second floor porch, perfect for morning coffee. The three first floor bedrooms have french doors that open to the pretty yard and offer easy access to the outdoor shower. The open floor plan boasts a cathedral ceiling, gorgeous kitchen, and a living area with gas fireplace. State of the art technology abounds: An elevator reaches three of the four floors, Central air keeps you cool and dry on hot summer days, a hardwired generator ensures non-stop power and protection for your appliances, sound proofing throughout the house keeps noise levels contained to each room, and a sprinkler system keeps the beautiful landscaping fresh. This home is ready for you to move in and unpack your bags!
Exterior
Map & Points of Interest
Block Island
Block Island is located in the Atlantic Ocean about 13 miles south of RI and is about 10 square miles. The Nature Conservancy named Block Island as one of twelve sites in its list of "The Last Great Places" in the Western Hemisphere.
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a406a1c2-7087-4b81-98b5-8886b570dbd1
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http://jc.residentialproperties.com/property/392353802/1808-mohegan-trail-block-island-ri-02807/
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Assist seniors with informal support to keep them living independently in their homes. Occasionally helping with bulk mailings – stuffing and labeling envelopes, working on special projects or special events. Being on-call to pick up a few items at the store, from the post office, at the pharmacy, etc. Light household chores.
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Sign up for our mailing list for project
opportunities and updates about our work!
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dcccfb0a-493f-473c-b49d-04822fdc067c
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https://developforgood.org/way-to-help/extra-hands-community-engagement-projects/
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2019-6-7 · By: Robyn Wilkinson 26th January 2018 The benefits of natural gas as fuel for boilers in industrial processes are too often overlooked by companies who continue to favour traditional coal-fired
2019-10-16 · The system was not a commercial success and the town reverted to gas. In 1882 the world's first coal-fired public power station, the Edison Electric Light Station, was built in London, a project of Thomas Edison organized by Edward Johnson. A Babcock & Wilcox boiler powered a
We are the exclusive distributor for the world's largest burner manufacturer, Riello, and offer their full range of burners, suitable for almost any fuel and equipment type.One of our other key suppliers, Limpsfield, is currently the only manufacturer who can guarantee O2 levels of below 3% across the firing range when using gas. One of the latest additions to our burner range Pelltech's
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7c92a44a-1653-443a-ae3c-9c4aa3bc36de
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https://wapmessage.de/27432-Town-Gas-Fired-Boiler-Manufacturer-In-Nigeria.html
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3i Infotech is a rapidly growing organization, in terms of both people and customers. To keep up with this rapid pace of growth, 3i Infotech is continuously seeking talented and focused individuals who can contribute significantly and be a part of this growth process.
Delhi Jobs
Delhi, the Capital of India is a homeland for plenty of jobs. With the span of companies from IT to mechanical, manufacturing to infrastructure, distributed across Noida, Gurgaon Delhi offers plenty of jobs to freshers, part timers, students, experienced persons in various industrial sectors etc.
We are constantly striving to provide you the latest job openings from Delhi. For feedback and suggestions for enhancement write to us.
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566112fe-ecdd-4823-8fca-da530fcbbdd1
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http://www.careersvalley.com/jobs-delhi/management-trainees-3i-infotech-limited-delhi
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1139
Objective: To compare the effectiveness of preload verses coload of crystalloid during spinal anesthesia for cesarean delivery
Study design: Randomized controlled trial
Place and Duration of Study: Department of Anaesthesia, Civil Hospital Karachi from 1st November 2017 to 30th April 2018.
Methodology: Sixty patients with age in between 18 to 35 years irrespective of parity having ASA physical status I and II and gestational age 37 completed weeks underwent cesarean section under spinal anesthesia were enrolled. Patients were randomized into one of two groups (P or C). A decrease of systolic blood pressure by 20% or more from the baseline value was taken as hypotension.
Results: The mean age, weight, height, BMI and gestational age of the patients was 29.5±4.83 years, 60.16±5.17 kg, 1.54±0.60 m, 27.04±5.07 kg/m2 and 38.13±1.07 weeks respectively. Efficacy was significantly higher 25 (83.3%) among patients in preload group as compared to coload group 17 (56.7%) [P=0.024].
Conclusion: Effectiveness of preload was found to be less than coload of crystalloid during spinal anesthesia for cesarean delivery
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7f0d5369-1872-428d-909d-317d0f598241
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https://pjmhsonline.com/published-issues/2021/may/1139
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ABOUT US
The Name and Idea of PUBLIC POLICE was concieved by Mr. Rakesh Kumar Maheshwari a Chartered Accountant, Having Professional Experience more than four Decades and Mr. Deo Datta, IAS (R) who Served the Nation relentlessly throughout his bureaucratic career spanning over more than Four Decades The "Public Police" has been incorporated as a Registered Trust (NGO) at Delhi. under the blessings of its chairman Mr. Justice K.G.Balakrishnan, Former Chief Justice of India and Ex-Chairman National Human Rights Commission with the guidence of
former High Court judges, former senior IAS Officers, former senior IPS Officers ,former law secretaries and some distinguished members of the civil society.
The Public Police will aim to establish itself as a trustworthy and reliable intercommunication link between society and law enforcement agencies. The role of the police is to protect the public and stop crime. Additionally, they are responsible for maintaining law and order in the country. A police force's effectiveness is not determined by the number of arrests or police action, but by the absence of criminal activity and violations of the law. Public trust in the police has eroded over time, and citizens are afraid to go to the police with complaints about harassment, when one should feel safe and protected when going to the police. Our goal is to portray the police as trustworthy and friendly friends who deal with crime effectively and provide care with compassion. In addition, there have been cases where the conduct of members of the law enforcement agencies has been questionable and some members of society may be potential law breakers. The NGO will serve as a bridge between the public and the police so that they can learn about each other.
A team from the NGO will create forums and send a team to visit communities so they are familiar with the rules and regulations. As a result, they understand that police personnel are also members of society and they have to act according to the legal system of the country. In difficult situations, police officers can do their duty with confidence and dedication, maintaining goodwill and support from the public while avoiding confrontation. The Police shall organize conferences, camps, events, and several other activities to promote education and public awareness so that mistrust can vanish and a regime of confidence can be introduced.
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cf3a1df4-8e0d-42f2-82d6-16f894ae102a
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https://www.publicpoliceindia.com/about-us.php
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Alert
AIR FORCE FAMILY SERVICES
Adult Education — Professional Military Education Center (Air Force)
The Binnicker Professional Military Education Center is a world-class institute that prepares enlisted air expeditionary warriors (ALS and NCOA) for the challenges of combat leadership. Most programs are offered in Hangar 2, Building 2060. In addition to Air Force professional and career development, all active-duty, ANG and Reserve personnel, dependents, retirees, federal employees, and adult family members with military ID cards can draw on the resources of seven colleges and one adult learning center. Call 808-449-2946 for more information.
Airman Leadership School improves the skills, leadership abilities and understanding of the military profession of first-time supervisors. The ALS course is five weeks long.
NCO Academy prepares NCOs for increased leadership roles and responsibilities, and lasts for six weeks.
The course curriculum for both the ALS and NCOA includes leadership, fit-to-fight, the profession of arms and communication skills.
Airman and Family Readiness Section (Air Force)
The Airman and Family Readiness Section provides Air Force Aid Society, Survivor Benefit Plan and casualty services for active-duty Air Force, retired Air Force personnel and their families. It is at 655 Vickers Ave., Building 1105, JBPHH. Hours are 7:30 a.m. to 4 p.m. Monday through Friday. For more information, call 808-474-1999.
Air Force Aid Society 808-449-0314/0301
Air Force Casualty Assistance 808-449-0310
Survivor Benefit Plan 808-449-0313
Air Force Aid Society: The AFAS is the official charity of the Air Force. It provides financial assistance with basic necessities such as food, rent, utilities, essential car repair, medical and dental expenses not covered by TRICARE, and emergency expenses resulting from a death or illness in the family. Assistance is provided as an interest-free loan, grant or a combination of both. The AFAS also sponsors numerous community enhancement programs:
Bundles for Babies provides parents-to-be with a free layette after attending the Military Family Support Center's New Moms and Dads class.
Child Care for PCS or Retirement provides up to 20 hours of child care expenses for members who are within 60 days of a departure PCS move or retirement.
Give Parents a Break provides eligible parents with five hours of free child care a month.
Child Care for Volunteers provides free child care for volunteers who support the 647th Air Base Group, 15th Wing, Pacific Air Forces and tenant organizations.
Car Care Because We Care provides grant assistance for a free oil change for first duty station personnel and spouses of deployed members.
Child and Youth Programs
Child Development Centers: CDCs provide a safe, healthy learning environment where children from 6 weeks to 5 years old can discover, learn and explore the world around them. Open to children of military and DOD families, there are several CDC locations on Joint Base Pearl Harbor-Hickam: Hickam Harbor, Hickam Main, Hickam West, Naval Station, Ford Island and Center Drive. Accredited by the National Association for the Education of Young Children, CDC staff are certified in CPR and first aid and trained in developmentally appropriate activities for young children. Sponsor of the USDA Child Care Food Program, CDCs offer nutritious meals and healthy snacks. For more information, call 808-471-5437.
Child Development Homes: This program provides quality child care through a network of certified home providers who live in Joint Base Pearl Harbor-Hickam housing. Home providers offer care for children ages 6 weeks to 12 years and provide developmentally appropriate activities in a home atmosphere. Child care hours are flexible to meet parents' needs. For more information, call 808-471-8658.
Kids Line: This free, convenient resource and referral service for child care is offered at Morale, Welfare and Recreation. Call 808-471-KIDS (5437) for info such as child care availability, subsidy and financial figures, waiting lists for CDCs, Child Development Homes and School-Age Care programs as well as programs offered throughout Hawaii.
MWR Youth Camps: During those much-anticipated school breaks, MWR Youth Programs offer day camps that are jam-packed with fun, trips and activities. Children can enroll in summer camps that focus on sports, outdoors or culture. For the winter, spring and summer breaks, children can play with other kids their age and have a blast at Camp Adventure. For more information, call 808-421-1556.
MWR Youth Programs: MWR has youth programs affiliated with the Boys & Girls Clubs of America and 4-H Extension Services on Oahu. The School-age Care Program operates sites at the Catlin Clubhouse and the Hickam SAC Building to offer child care before and after school hours. Serving children 5 to 12 years old, the centers offer fun activities in arts and crafts, games, healthy snacks and help with homework. Catlin is open only to children attending Aliamanu, Pearl Harbor and Pearl Harbor Kai elementary schools. The Teen Center also provides a safe after-school environment for kids 12 and older to go to work on homework, play and participate in clubs. For more information, call the Catlin Clubhouse at 808-421-1556, Hickam SAC at 808-448-4396 or the Teen Center at 808-448-0418.
MWR Youth Sports: When they join the MWR Youth Sports Program children and teens, ages 3 to 18, will learn teamwork, sportsmanship and other valuable lessons. Most youth sports teams are part of the Hawaii Military Youth Athletic Association, and sports including soccer, basketball, baseball and football are offered. Spirited sideliners can help lead the team to victory by cheerleading, and volunteer coaches are always needed. Get involved and be a part of this winning team. For more information, call 808-473-0789.
Force Development Flight
Located in Building 2060, Hangar 2 at 900 Hangar Ave., Force Development Flight provides educational opportunities through eight on-base institutions. The flight is responsible for base training, formal training, military testing, First Term Airman's Center and Career Assistance Advisor programs. The Base Training and Education Services element provides tuition assistance support, educational and vocational advising, testing opportunities and distance learning information. Several degree programs are available on Joint Base Pearl Harbor-Hickam for military, DOD personnel and family members.
Wayland Baptist University
For more information, call 808-449-6363 or email [email protected]. Active-duty Air Force members can access information on the Air Force Virtual Education Center via the Air Force Portal.
Military and Family Support Center
Joint Base Pearl Harbor-Hickam's MFSC provides services to support sustained mission readiness and strengthen personnel and family competencies to meet the unique challenges of the military lifestyle. Professional services through educational classes and counseling are available for active-duty Navy, Air Force, Reserve and retired personnel, their families and Department of Defense civilians.
Counseling and Advocacy Services: Professional counseling is offered to eligible individuals, couples, families and children. Immediate intervention, safety and support are provided to victims of child and domestic abuse, and rehabilitation and counseling are offered to offenders to eliminate the risk of future abuse. Services include crisis intervention, short-term counseling, victim advocacy, referrals, groups and classes facilitated by licensed clinicians.
For information on confidential reporting of domestic abuse, call MFSC and ask to speak to a victim advocate.
Crisis Response: The center stands ready to offer assistance and support to families during natural disasters, mobilization, repatriation and mass casualties.
Deployment Support: The center plays a key role by helping commands prepare crew and family members for the various phases of deployment. MFSC participates in predeployment, deployment and reunion programs.
Exceptional Family Member Program: This program assists families with special needs (for example, physical or emotional disability, long-term chronic illness or special education) so that the command, the EFMP at Tripler Army Medical Center and the EFMP liaison at MFSC can work together to ensure needs are met.
Family Employment Readiness Program: The center helps with career decisions and to develop employment search skills through education, information, referral and assistance programs, giving family members the competitive edge to secure employment. Some of the employment classes offered are resume writing, interviewing skills, starting your own business and federal employment.
Information and Referral: The center provides on- and off-base information and resources and maintains a resource databank with military and civilian resources providing community educational, life-enhancing and therapeutic resources. I&R also processes requests for registration for classes and workshops, schedules appointments and provides assistance. Through assessment, I&R refers crisis issues.
Joint Employment Management System: JEMS is an employment program open to all eligible military ID card holders. Its online job bank links military community job-seekers with employers in Hawaii. JEMS lists positions on the main Hawaiian Islands. At you can search for jobs, post your resume and receive notification when new jobs are posted.
The JEMS Job Fair is held every September on Joint Base Pearl Harbor-Hickam. It is the largest military job fair in Hawaii. More than 100 employers attend with local, mainland and international jobs. For more information, call 808-474-1999.
Life Skills Education: Provides education, awareness and prevention programs to promote understanding of risk factors and dynamics of child abuse and domestic abuse to commands, individuals, couples, families and community groups. The classes and programs address parenting, suicide prevention, stress and anger management, and new military spouse orientation.
Military School Liaison Office: Call the School Liaison Office at 808-422-3770/3771.
New Parent Support Home Visitation Program: A voluntary early intervention program serving Navy, Air Force and Coast Guard families who are expecting a child or with a child under 3 years of age. Services promote healthy family functioning, teach new skills and support military families facing the unique challenges of parenting. A New Parent Support Group is also available. The New Moms and Dads class is offered monthly by the New Parent Support staff.
Readiness Program: MFSC offers mobility and deployment assistance to single and married active-duty Air Force personnel and families. MFSC provides predeployment education briefings for deploying members and families; sustainment support services such as morale calls, information and referral services; and referral to applicable Air Force Aid Society programs such as "Give Parents a Break" and "Car Care Because We Care."
Retired Activities Office: Volunteers help retirees, their survivors and family members to obtain their rights and benefits. The office holds an annual retired personnel seminar and publishes a biannual newsletter.
Sexual Assault Prevention and Response: The Hickam Sexual Assault Response Coordinator office provides 24/7 sexual assault response for all victims on the installation and assigned geographically separated units. Anyone who feels he or she has been a victim of sexual assault may contact the SARC office. The Hickam SARC Response Helpline is available 24/7 at 808-722-6192. For more information, go to
The SARC recruits, coordinates and trains active-duty and DOD civilian personnel to become SAPR victim advocates who are available 24/7 to provide immediate support to adult active-duty personnel and family members of sexual assault. The SARC also conducts training for command personnel designated to be the SAPR Command POC, command liaison and data collection coordinator.
Spouse Support Groups — Key Spouse: Key Spouses are a part of the command team and are an essential link to a healthy family. The program is an official communication network designed to enhance readiness and establish a sense of community among unit leaders, airmen and their families.
Transition GPS (Goals, Plans, Success): Whether you are retiring or separating, the center can help with your transition from the military life to the civilian world. Transition seminars for retiring and separating personnel are available.
Volunteer Program: Volunteering may lead to employment in addition to the satisfaction of helping others. Ask for the MFSC volunteer coordinator for more information.
Religious Ministry
Whatever one's faith, finding a place to worship after a PCS move can be challenging. The Joint Base Pearl Harbor-Hickam chaplains are available to help you find a place of worship and take the next step with you in your spiritual journey. There are a number of opportunities to get plugged into a worshipping community at the installation chapels. Besides worship services, religious programming is available for people of all ages, including Bible studies, Vacation Bible School, other services and social events. For more information, call 808-473-3971 (Pearl Harbor Memorial Chapel) or 808-449-1754 (Hickam Chapel Center).
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http://mybaseguide.com/joint_bases/94-3021/joint_base_pearl_harbor_hickam_air_force_family_services
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13.2. Ce Dispozitiv STONITH Ar Trebui Să Folosiţi
It is crucial that the STONITH device can allow the cluster to differentiate between a node failure and a network one.
The biggest mistake people make in choosing a STONITH device is to use remote power switch (such as many on-board IMPI controllers) that shares power with the node it controls. In such cases, the cluster cannot be sure if the node is really offline, or active and suffering from a network fault.
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268492b2-5264-4c59-bc0c-487ebff91819
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https://clusterlabs.org/pacemaker/doc/deprecated/ro-RO/Pacemaker/1.1-plugin/html/Pacemaker_Explained/_what_stonith_device_should_you_use.html
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#302169 (-38/168) ↑Funny↓Bad⚐Flag <scgtrp> froggey: [Link to circuit diagram]
<scgtrp> what's that thing above the transistor?
<froggey> a diode and a thing
<scgtrp> yes, what's the thing?
<froggey> dunno
<froggey> solemnwarning?
<solemnwarning> It's a box with a diagonal line through it
<froggey> that's what i thought
* scgtrp facepalms.
<froggey> scgtrp: go find a box with a diagonal line through it-+
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4b0a4706-d5c2-4f18-b961-f29e16868ef9
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http://qdb.us/302169
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20210418-MMPI0083
Sunday 18th April 2021 saw the first Watts for Breakfast fly-in for some time at Watts Bridge Memorial Airfield (YWSG). The event also hosted practice for Red Thunder aircraft in preparation for their Red Thunder TFC event. Over 60 aircraft attended the fly-in with owners enjoying a hearty cooked breakfast and having a chance to catch up with their aviation colleagues. For me it was a busy day, trying to cover as many landings and takeoffs as I could from 7am to after 1pm.
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5367b229-c450-4082-8fcd-43677a70255f
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https://galleries.mmpi.biz/Galleries/Aviation/Aircraft-by-JobID/2021/20210418-MMPI0083
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639 Hz - The Tone of Tender Yearning . The Miracle Tone of Emotion and Fondness. The Symphony of Love and Passion. Thats what describes this 639Hz Music. And we call this series - Travel Through Cosmos with Angels. Because it felt like we are travelling through it, and if you think deeply we all are.. travelling through this vast cosmos... and along with the angels.. and this music seems like a lullaby sung by angels... Hope you will like it. Infinite Love and Gratitude. Copyright ⓒ 2017 Meditative Mind. All Right Reserved.
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bdac4f75-0725-469b-a4ce-092a6f9b0120
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https://music.ava360.com/639hz-%E2%9D%AF-travel-through-cosmos-with-angels-%E2%9D%AF-angelic-music-%E2%9D%AF-attract-love-%E2%9D%AF-cosmic-music_758218732.html
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Biology Inhabit mid-waters along steep outer lagoon and seaward reef drop-offs. Also found along rocky shores. Benthopelagic. Usually in small groups but form large schools in oceanic locations or on reefs subject to strong currents. Juveniles and subadults feed on benthic algae; adults feed on zooplankton. Pair spawning has been observed. Caught with nets annulatus (Quoy & Gaimard, 1825) - Reported from New Caledonia - Link to the species (here). Plain brown or olivaceous in color, paler below; subadults with black caudal rays, narrow margins and white caudal filaments; pectoral fins with white distal margins. Naso unicornis (Forsskål, 1775) - Reported from New Caledonia - Link to the species (here) - Presence of a tapering body horn in adults projecting anteriorly at level of eye but not extending in front of mouth.
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ce99d5ea-7afe-431a-9a56-77f115e511be
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http://www.picture-worl.org/actinopterygien-nouvelle-caledonie-2a1-naso-brevirostris-cuvier-18296.html
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0634037366
9780634037368
Contemporary Music Theory - Level Three:(Piano). This book is the product of Mark Harrison's experience teaching hundreds of students at the world-famous Grove School of Music in Los Angeles. Suitable for instrumentalists, vocalists, composers and songwriters, this Level 3 course covers the chord tones, extensions and scale sources for all major, minor, dominant and diminished chords, and then applies the contemporary shape concept to create voicings, polychords, and to harmonize melodies.
Back to top
Rent Contemporary Music Theory - Level Three 1st edition today, or search our site for Mark textbooks. Every textbook comes with a 21-day "Any Reason" guarantee. Published by Hal Leonard Corporation.
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bac17649-3af6-4e28-93af-8dc725c71d1a
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http://www.chegg.com/textbooks/contemporary-music-theory-1st-edition-9780634037368-0634037366?ii=14&trackid=04c3aef0&omre_ir=1&omre_sp=
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A Family & Kids Festival organized by Septemberfest Commission.
This Illinois Family & Kids Festival will have fine art, fine craft, crafts, corp./information and antique/collectibles exhibitors, and 15 food booths. There will be 1 stage with National and Local talent and the hours will be Sat 11am-10pm. This event will also include: parade, games, demonstrations, car show, live deejay and rock band.
November 2019(dates not updated) Event promoter has not updated for this year, last year's event was November 10, 2018 CCW Holiday Craft Show Saint Isidore Ministry Center,427 W. Army Trail Road,
60108
A Craft Show organized by Saint Isidore Council of Catholic Women.
This Illinois Craft Show will have fine art, fine craft and crafts exhibitors, and no food booths. Admission tickets are $2. This event will also include bake sale.
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f66e2692-0b7b-4dfd-94d9-2e6b75c74271
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https://festivalnet.com/state/illinois/Bloomingdale_IL.html
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2009/4/8 dailos <dailos.guerra.r_at_gmail.com>:
> Hi Simon,
>
> Thank you for your reply.
> I've partially sorted the problem out.
>
> The repository is already set up.
> Both my working copy and the repository are in Unix machines.
> Although I can access them from my Windows PC either via Samba or X-
> Win.
You should NOT be using TSVN on working copies that are also accessed
by Unix Subversion clients. The working copy format for Unix and
Windows is not necessarily compatible and mixing Windows and Unix
clients can cause problems.
> I did not do a checkout since I had got a working copy already. I
> got the copy using our custom checkout tool from Unix. And I guess It
> uses "svn checkout" command internally.
>
> But after checking a single module out using Tortoise, everything
> seemed to work properly for these files.
> ¿Does it mean our Unix checkout tool is not compatible with
> Tortoise? ¿Is there a way to bypass the problem?
The problem you reported indicates that indeed you suffer from
incompatibilities between the two clients
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66840c69-6ddd-4286-875f-9b015b797680
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https://svn.haxx.se/tsvnusers/archive-2009-04/0230.shtml
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Association News and Publications
On November 21, Canada's environment minister Catherine McKenna announced the country's plan to virtually eliminate the use of traditional coal-fired electricity by 2030. However, Ottawa recognizes that provinces need flexibility and is willing to negotiate agreements that would allow some plants to stay open so long as equivalent emission reductions are achieved elsewhere. The federal government has agreed to negotiate a deal with Nova Scotia that will allow the province to burn some coal after 2030 in high-demand winter months, while it achieves deep emissions reductions in its electricity sector.
In 2014, EU Member States agreed on a new Climate and Energy Framework that sets new targets for the year 2030: (1) at least 40 per cent cuts in GHG emissions (from 1990 levels), (2) at least 27 per cent share for renewable energy, and (3) at least 27 per cent improvement in energy efficiency.
When handled properly, wood pellet fuel is safe and benign. Wood pellets are made by drying and compressing pure wood particles. Naturally occurring lignin softens during pelletizing and then hardens during the cooling process to bind wood particles together as pellets. It is hard to imagine how such a pure product could be dangerous.
With the wood pellet industry hurting from low fuel prices, warm winters, and unhelpful government policies in many countries, is there a light in the gloom? The potential of global markets was the topic de jour during the annual Wood Pellet Association of Canada conference, which took place in Harrison Hot Springs, B.C., Sept. 20-22.
The Netherlands (NL) was briefly the world's largest importer of industrial wood pellets for co-firing. Under its former biomass support scheme - Milieukwaliteit van de Elektriciteitsproductie or MEP – wood pellet consumption for co-firing peaked at about 1.5 million tonnes annually. However, from 2012 and 2014, imports declined rapidly and eventually stopped altogether, as power utilities' MEP contracts expired.
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e33bf786-6eb6-44aa-9924-438d381e1f19
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https://www.pellet.org/wpac-news/Page-14
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316.2 Effect on acquisitions and condemnations.
1. The provisions of this chapter shall not affect the validity of any
property acquisitions by purchase or condemnation.
2. Nothing in this chapter shall be construed as creating in any
condemnation proceedings brought under the power of eminent domain, any element
of value or of damage not in existence immediately prior to the date of this
chapter.
3. A payment made or to be made under the authority
granted in this chapter shall be for compensating or
reimbursing the displaced person or owner of real property in
accordance with the requirements of the federal Uniform
Relocation Act and this chapter and the payments shall not for
any purpose be deemed or considered compensation for real
property acquired or compensation for damages to remaining
property.
Payments authorized to be made by the federal Uniform
Relocation Act and this chapter shall be made as relocation
payments, and in order to prevent unjust enrichment or a
duplication of payments to any condemnee in any condemnation
proceeding or appeal from any condemnation proceeding, an
allowance shall not be made in determining just compensation
in a condemnation proceeding for any damages, for any item of
damage, or any cost, which is authorized to be paid as a
relocation payment.
Moving cost payments and allowances for personal property
which is damaged or destroyed or reduced in value by an
acquisition of property authorized under section 6B.14 or any
other provision of the Code under the powers of eminent domain
on projects where relocation assistance payments are paid
under this chapter shall be those payments and allowances
authorized by this chapter and shall not be made or included
as part of an award of damages in any condemnation proceeding
or appeal from any condemnation proceeding.
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aba3c1dc-fb59-4b9f-91bc-b93d3e859e66
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https://www.legis.iowa.gov/DOCS/IACODE/1999/316/2.html
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26 March 2017
Want to receive a spirit message through your cards?
Would you like to use your cards to receive a message from a deceased loved one or a particular spirit guide?
Assign them a significator, a card that will be their "place holder" in the deck. For example, for me, my mother always appears as the Queen of Diamonds* when using playing cards, and the Bouquet when using Lenormand.
Shuffle the deck and then thumb through it face up until you find their card. The card before (on top of) it reflects what they want to talk about or how they're feeling, and the two cards behind (below) it expand on the subject or form the message about the first card.
Need more information from them or want to ask a question? Reshuffle and repeat the process. Don't overdo it though. When you start getting jibberish is when you know you've worn them out. 😉
*Because in traditional German courts this Queen is holding a carnation, my mother's favourite flower.
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2e4bf984-f1be-474c-a61e-d87aa9624ba2
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http://cartomancy-corner.blogspot.com/2017/03/want-to-receive-spirit-message-through.html
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15 marzo 2007
DAWN HERNANDEZ
Dawn Hernandez is an American Artist living on the East Coast. She is a devoted mother, and a Jersey Girl, through and through. So much so, her eBay id is jerseygirl613!
Dawn is a talented mixed media artist and has parlayed her skills into a business providing wonderful supplies for other mixed media artists as well. Dawn is well verwsed in creating Artist Trading Cards, Art Dolls, and other mixed media art pieces, and as of late she has been creating fun altered bracelets and jewelery. Her website and eBay store provide collage sheets, rubber stamps, and collage packs to discerning artists.
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eng
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3332b93c-6dd5-452c-9139-895d13cfbd15
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http://chelise.typepad.com/spirito_di_zne/2007/03/dawn_hernandez.html
| 1medium-low
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: 10 Mistakes that Most People Make
Search Engine Optimization or SEO is the art of enhancing internet site traffic to an internet site by utilizing very efficient back links. Back links are incoming web links from various other sites that directed site visitors to the internet site concerned. There are different back links approaches utilized for enhancing website traffic. The purpose of this article is to discuss high-grade backlinks, why they are essential as well as how you can obtain them.
One method to acquire back links is via premium backlink entry to a high-traffic internet directory such as Yahoo! Each of these directory sites enables you to browse for backlinks to your web site.
One more strategy that you might consider for getting top quality back links is doing visitor blogging on other individuals's blog sites. Visitor blogging enables you to create as well as release fresh content about topics connected to your website. Numerous web designers enable you to do-follow back links on their blog site with a process called "dofollow." They merely enable you to put a backlink to your very own site within the body of your short article.
Another method to get backlinks is via premium DO follow directory sites like DMOZ, Yahoo!, and also Google+. By adding your LINK to these directory sites you are actually making it more likely that your link will certainly be clicked on by an individual looking for details pertaining to your website. This is among the most effective means to get highly targeted back links since these are high-quality backlinks that were already located by users before they clicked your web link. If you have an account with these types of sites, make sure that you maintain your profile updated to ensure that site visitors will frequently see your back links. This can boost the chance of your website showing up in internet search engine results when someone look for terms associated with your web site.
If you have a lot of time on your hands, one more terrific strategy for getting top quality back links is with freelance work. There are many people that use their skills as writers to make money online. Rather than starting your very own freelance organization, you can instead use your proficiency as a writer to develop high quality content for websites and also blog sites that require top quality material and also paid-per-click advertising campaigns.
The last Back links Techniques I'll talk about entails making use of directory entry services. Directory site submission solutions use a number of different bundles that you can purchase and send your web site to.
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eng
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d57427d9-2014-4001-af8d-15964abe23e1
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https://deaideai.info/10-mistakes-that-most-people-make-4/
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A Doctor, a Lawyer, and a Priest
A Story
The Colonel stepped out of his office and looked to his right, down the corridor to the narrow barred window at the end. Light snow was falling on the courtyard, and he caught a brief glimpse of the transport truck as it completed the tricky backup maneuver to the loading platform and ceased its persistent beeping. Patting his chest, he softly belched and savored the memory of an early lunch—imported Dorchester cheddar on brown bread with bits, washed down with a frothy pale ale. It had been the highlight of a very dull morning, which consisted of several long bouts of paperwork and a lackadaisical victory over a plodding opponent in a game of online chess.
He turned to his left. Ten prisoners sat on a long wooden bench. Above them, halfway up the cracked, peeling wall, was a row of numbers—one through ten—painted yellow and outlined in black. Below the numbers, directly behind the shaved heads of the prisoners, were ten, murky, egg-shaped stains—historical evidence of the thousands of perspiring skulls that had leaned against the cold concrete
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eng
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35735294-c3af-4256-8348-d5a98f289ddb
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https://www.narrativemagazine.com/issues/stories-week-2010-2011/story-week/doctor-lawyer-and-priest-david-sipress
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A modern way to reach masses
CHICAGO — Standing
"Could we be at one of these moments in history where technology, if we leverage it correctly, could transform how we engage in the Bible?" Gruenewald, 37, recalls thinking that day. "Drawing from the story of the printing press, for centuries, that really changed our access to the Bible. It's probably something today we easily take for granted, but it came through invention
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eng
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941156f5-9e49-4451-a25d-0b02c7c1e173
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http://www.wenatcheeworld.com/news/2013/oct/25/a-modern-way-to-reach-masses/
| 3medium-high
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12/2019 12:00:00 AM2020-01-10T00:00, fluid and intentional. That can be described in one of our core Leadership Principles, which is Bias for Action. This means that our teams band together, roll up their sleeves, and aren't content with just standing still. We're aiming to become the most customer-centric company on Earth.
Shift Assistants are part of the Last Mile operations in Amazon Logistics and play a crucial role in this rapidly growing team. Shift Assistants are responsible for daily management of department duties including: allocating labor, leading meetings, assigning job duties, providing work direction and communicating with internal and external suppliers.
Responsibilities:
* Track and report ATS/labor hours
* Occasionally, assist with production duties, train associates and verify SOP (standard operating procedure) compliance
* Ensure successful area performance through tracking and reporting metrics
* Independently assess all aspects of associate work performance and provide timely and detailed feedback
* Participate in Operational Excellence initiatives
* Maintain a full understanding of workflow and daily production goals
* Review and update SOP's as required
* Ensure work areas remain clean and are properly equipped
* Identify and address safety hazards within the work area, and participate in safety initiatives
* Coach associates on ways to work safely at all times
* Ensure all job injuries are reported timely in accordance with established policies and procedures
* Provide vacation coverage for Area Managers
Amazon.Com, Inc.CincinnatiOH Part Time Teller within PNC's Retail Branch organization, you will provide exceptional customer service, accurately perform high volume customer banking transactions, educate customers on new technology and develop banking product referral opportunities through strong customer relationship skills.This position will be based in Cincinnati, OH at the Western Hills retail banking branch.
Job Description
* Delivers a unique customer experience aimed at improving customer financial wellbeing and creating loyalty while increasing share of wallet. Processes a variety of customer interactions. Educates customers on alternatives available for their financial interactions. Identifies banking opportunities during the customer interaction and refers as appropriate.
* Identifies opportunities through meaningful conversations with customers, making appropriate referrals to branch staff or PNC ecosystem partners.
* Performs lobby engagement activities to connect with customers and position PNC products to meet their needs. Educates customers on options for managing financial transactions by leveraging technology, tools and resources.
* Applies product and procedural knowledge to solve customer's problems.
* Adheres to all policies and procedures, demonstrating sound judgment within established limitsAccuracy and Attention to Detail – Understanding of the necessity and value of accuracy and attention to detail; ability to process information with high levels of accuracy.
Addressing Customer Needs – Knowledge of and ability to meet customer needs by offering appropriate products in an appropriate manner. or any significant experience or product knowledge to accomplish primary duties. Prior experience is not required
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eng
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de20777a-4c92-4544-bee1-d7d7e0cd9048
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https://jobs.livecareer.com/l/macys-locker-room-assistant-manager-parttime-lids-72e627d1677d8a2c14e979b40b69d6cc
| 2medium
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Abstract
Purpose: The COVID-19 pandemic has resulted in vital implications for tourism education and curricula, and the education effectiveness in times of crisis ought to be resilient in the light of its preparedness, response and recovery policies and research. Purpose of the study is to analyse the academic practices in tourism education with a specific focus for incorporating the resilient adaptation strategies.
Design/Methodology/Approach: The study is conducted using content analysis of published data along with interviews with heads of the tourism educational institutions.
Findings: Very few universities are offering courses on resilience and disaster management as part of the curriculum in the tourism study programmes.
Originality/Value: The chapter provides strategies on the effective integration of resilient tourism policy and practices as mitigation measures into the tourism education system with a special emphasis on disaster prevention, mitigation and vulnerability reduction at the destinations in the post-COVID-19 scenario.
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eng
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f32068a7-3721-406d-a0a7-7e3a45e0803f
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https://www.emerald.com/insight/content/doi/10.1108/978-1-80071-511-020211020/full/html
| 3medium-high
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anandamide
an·an·da·mide
(an-an'dă-mīd),
N-arachidonoylethanolamine, a brain lipid that binds to cannabinoid receptors; also found in cocoa.
anandamide
(ə-năn′də-mīd′)
n.
A neurotransmitter, C22H37NO2, found especially in the brain, that binds to the same receptors as cannabinoids and influences mood, appetite, motivation, perception of pain and pleasure, and memory. Anandamide is also found in small amounts in cocoa and chocolate.
anandamide
(ă-nan′dă-mīd″) [Sanskrit ananda, endlessness, eternal bliss + amide]
A neurotransmitter that binds to and activates cannabinoid receptors on brain cells.
Amides and its derivatives are an important functionality in both natural and synthetic bioactive compounds such as niacin amide is vitamin B [1] fatty acid amides, anandamide is analgesic [2] oleamide that is present in cerebrospinal fluid induces sleep [3] while erucamide stimulates formation of new blood vessels [4] and a natural painkiller found in brain peptide is enkephalins [5].
Finally, other investigators identified a third type of LTD in the BNST that was dependent on mGluR5-mediated generation of the lipid signal anandamide, which then acted on postsynaptic transient receptor potential V1 (TRPV1) channels (Puente et al.
It has been reported that endogeneous cannabinoids including anandamide show negative inotropic and antiarythmical action by way of voltage-gated sodium channels and L-type calcium channels independent of sympathetic
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eng
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fdb7ed9d-cc1f-435d-b656-0f64eed27a02
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http://medical-dictionary.thefreedictionary.com/anandamide
| 4high
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Amanda Owen Shepherdess
Just seen the book recommendations have Celebrating the seasons with the The Yorkshire Shepherdess by Amanda Owen. I have watched her on telly for years and was given the book for my birthday. It was a fantastic read and wonderful photography of her family and the farm. For me sheep are the star attraction but anyone with an interest in the rural life I would recommend getting a copy.
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eng
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93740299-1965-4ac5-9d8d-a6bd3e528194
|
https://www.amateurphotographer.co.uk/forums/threads/amanda-owen-shepherdess.143618/
| 1medium-low
|
Add a touch of exuberant style to your décor with this beautiful Dale Tiffany Festive Ruffle Vase. This stunning hand-blown object features vibrant geometric shapes on a blue background and a prettily ruffled top of clear glass.
It wouldn't be Christmas without the iconic Spode Christmas Tree collection. The epitome of fine holiday entertaining since its introduction in 1938, this beloved pattern beautifully captures the festive spirit of the seasonTransform your meal into a royal affair with the opulent Wedgwood® Renaissance Gold Salad Plate. Reminiscent of Europe's Renaissance period, the salad plate is embellished with a deep blue border and gold trim.
Commemorate the career of one of the New York Yankees' most beloved players, Derek Jeter, with this Steiner Derek Jeter Moments World Baseball Classic Plaque. Featuring a picture of Derek mid-swing, this plaque is a must have for any Yankee fan
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eng
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b25d3acc-bed5-49a3-b350-adf5d356aecb
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http://www.bedbathandbeyond.com/1/1/indexd1608.html
| 0low
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According to an annual survey of the Bering Sea floor carried out by the National Oceanic and Atmospheric Administration, estimates for the crustaceans' total numbers fell to about 1.9 billion in 2022, down from 11.7 billion in 2018, or a reduction of about 84 percent.
For the first time ever, the Alaska Department of Fish and Game announced the Bering Sea snow crab season will remain closed for 2022-23, saying in a statement efforts must turn to "conservation and rebuilding given the condition of the stock." The state's fisheries produce 60% of the nation's seafood.
The species is also found in the more northward Chukchi and Beaufort Seas, but they do not grow to fishable sizes there.
Erin Fedewa, a marine biologist with the Alaska Fisheries Science Center, told AFP the shocking numbers seen today are the result of heatwaves in 2018 and 2019.
The "cold water habitat that they need was virtually absent, which suggests that temperature is really the key culprit in this population decline," she said Ben Daly, a researcher with ADF&G, told CBS NewsHistorically an abundant resource in the Bering Sea, their loss is considered a bellwether of ecological disruption.
There are thought to be several ways that warmer temperatures have depleted the species.
Studies have pointed toward a higher prevalence of Bitter Crab Disease as the temperature heats up.
The crustaceans, named for their love of cold water, are also under greater metabolic stress in warmer waters, meaning they need more energy to stay alive.
"A working hypothesis right now is that the crabs starved, they couldn't keep up with metabolic demands," said Fedewa.
Young snow crabs in particular need low temperatures to hide out from their major predator, Pacific cod, and temperatures in regions where juveniles typically reside jumped from 1.5 degrees Celsius in 2017 to 3.5 Celsius in 2018 (35 degrees Fahrenheit to 38 degrees Fahrenheit) — with studies indicating 3C might be an important threshold.
More research is underway and findings should be published soon, but in the meantime, "everything really points to climate change," Fedewa said.
"These are truly unprecedented and troubling times for Alaska's iconic crab fisheries and for the hard-working fishermen and communities that depend on them," Jamie Goen, executive director of Alaska Bering Sea Crabbers said in a statement, lamenting that second and third generation crab-fishing families "will go out of business."
The industry was also hit by the cancellation of Bristol Bay red king crab fishing for the second year in a row.
Fedewa also noted that overfishing isn't a big factor in the population collapse of snow crabs.
Fishing removes only large adult males, she said, "and we've seen these declines across all sizes of snow crab, which really suggest some bottom-up environmental driver is at play."
Male Alaska snow crabs can reach six inches (15 centimeters) in shell width, but females seldom grow larger than three inches, according to NOAA.
In some good news, this year's survey saw significant increases in the immature crabs compared to last year — but it will take four or five years before the males among them grow to fishable size.
Following the heatwave years, temperatures have returned to normal, and "the hope is that leaving crabs untouched will allow them to reproduce, there'll be no mortalities, and we can just let the stock try to recover," said Fedewa.
Gabriel Prout, whose Kodiak Island fishing business relies heavily on the snow crab population, told CBS News that there needs to be a relief program for fisherman, similar to programs for farmers who experience crop failure, or communities affected by hurricanes or flooding.
When asked what fishermen can do in this situation, with their livelihoods dependent on the ocean, Prout responded, "Hope and pray. I guess that's the best way
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eng
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8969aea0-c59e-4652-8a8b-7a5c92f0981e
|
https://news.yahoo.com/expert-identifies-key-culprit-mass-150918200.html/
| 3medium-high
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Abstract:
The present invention relates to a method of fabricating a zinc-air cell
and a zinc-air cell fabricated using the same. The zinc-air cell includes
a cup adapted to function as a sealant of the cell, a film adapted to
function as an anode of the cell and bonded on the cup, wherein the film
has a first surface with a hydrophobic property and a second surface with
ion permeability, and the second surface comes in contact with the cup,
and a zinc gel adapted to function as a cathode of the cell and filled
between the cup and the sealant. The method of fabricating a zinc-air
cell includes preparing a cup having a central portion of a downward
depressed shape and functioning as a sealant of the cell, bonding a film
adapted to function as an anode of the cell on the cup, and filling a
zinc gel, which functions as a cathode of the cell, in a space between
the cup and the sealant.
Claims:
1. A zinc-air cell, comprising:a cup adapted to function as a sealant of
the cell;a film adapted to function as an anode of the cell and bonded on
the cup, wherein the film has a first surface with a hydrophobic property
and a second surface with ion permeability, and the second surface comes
in contact with the cup; and a zinc gel adapted to function as a cathode
of the cell and filled between the cup and the sealant.
2. The zinc-air cell of claim 1, further comprising:a cathode terminal
drawn from the zinc gel to the outside of the cell and transporting
electrons, which are generated by a chemical reaction in the zinc gel;
andan anode terminal for supplying electrons from the outside to the film
such that a chemical reaction can be generated in the film adapted to
function as the anode.
3. The zinc-air cell of claim 1, wherein the first surface is formed of
Teflon material, and the second surface is formed of polypropylene
material.
4. The zinc-air cell of claim 1, wherein the cup is formed of
polypropylene material.
5. The zinc-air cell of claim 1, wherein the cup is formed of the same
material as that of the second surface of the film.
6. The zinc-air cell of claim 2, wherein the film has a multi-layered
structure including a metal mesh, and the anode terminal is formed by
removing a layer on a top of the metal mesh in one end of the film and
exposing the metal mesh.
7. The zinc-air cell of claim 1, wherein the cathode terminal has a shape
curved in an S shape or C shape.
8. A method of fabricating a zinc-air cell, comprising:preparing a cup
having a central portion of a downward depressed shape and functioning as
a sealant of the cell;bonding a film adapted to function as an anode of
the cell on the cup, wherein the film has a first surface with a
hydrophobic property and a second surface with ion permeability, and the
second surface comes in contact with the cup; and filling a zinc gel,
which functions as a cathode of the cell, in a space between the cup and
the sealant.
9. The method of claim 8, further comprising:inserting a cathode terminal
for carrying electrons, which are generated in the zinc gel, into the
zinc gel and drawing the cathode terminal outside the cell; and forming
an anode terminal for supplying electrons to the film.
10. The method of claim 9, wherein:the film has a multi-layered structure
including a metal mesh, andforming the anode terminal includes removing a
layer on a top of the metal mesh in one end of the film and exposing the
metal mesh.
11. The method of claim 8, wherein the bonding is performed using bonding
employing heat fusion, ultrasonic fusion or a bonding agent.
12. The method of claim 8, further comprising curving edges of the cup in
a shape that can surround the film so that the film is depressed in the
edges of the cup.
13. The method of claim 8, wherein the cup is formed of the same material
as that of the second surface of the film.
14. The method of claim 8, further comprising curving the cathode terminal
in an S shape or C shape.
Description:
TECHNICAL FIELD
[0001]The present invention relates to a method of fabricating a zinc-air
cell and a zinc-air cell fabricated using the same, and more
particularly, to a zinc-air cell of a rectangular parallelepiped shape,
which is applicable to, for example, a cellular phone battery.
BACKGROUND ART
[0002]As conventional means for supplying power to electronic devices, a
battery was widely used. The primary cells, such as manganese cells,
alkaline manganese cells, and zinc-air cells, and the secondary cells,
such as nickel cadmium (Ni--Cd) cells, nickel hydride (Ni--H) cells, and
lithium ion cells, were used as the conventional cells. Of them, the
zinc-air cell is advantageous in that it provides a relatively high
voltage of 1.4 V, and has a high energy density and a great discharge
capacity. Further, the zinc-air cell has an almost constant discharge
characteristic until the discharge of the cell is completed and has
therefore been considered to be able to replace the mercury cell whose
use is prohibited since it contains heavy metal.
[0003]FIG. 1 is a sectional view of a conventional button shape zinc-air
cell. Referring to FIG. 1, the conventional button shape zinc-air cell
includes a membrane 10 as an anode, and a zinc gel 16 as a cathode. A
separator 12 is intervened between the membrane 10 and the zinc gel 16.
Further, the membrane 10 and the zinc gel 16 are accommodated within a
conductive anode can 18 and a cathode can 20, respectively, thus
constituting a cell.
[0004]The membrane 10 is a permeable membrane including water molecules
and comes in contact with oxygen in the air, thus generating hydration
ion OH-. This reaction can be represented by the following Chemical
Formula.
[0005]ChemistryFigure 1
O2+2H2O+4e-4OH- [Chem. 1]
[0006]In the above reaction, electrons are supplied through the anode can
18. Material of the membrane generally includes carbon, but may employ a
proper material according to a necessary voltage or an application field.
[0007]Since oxygen is required in the reaction in the anode as described
above, the anode must have a path which can come in contact with the air,
and therefore air holes 14 are formed at the bottom of the anode can 18.
The air holes 14 are sealed when the cell is not used so as to prohibit
the reaction in the anode.
[0008]Hydration ions generated by the above chemical reaction are
transferred to the zinc gel 16, that is, the cathode through the
separator 12. The separator 12 has permeability with respect to hydration
ions and functions to prevent the leakage of the zinc gel 16 and insulate
the zinc gel 16 and the membrane 10 from each other.
[0009]The zinc gel 16 includes zinc powder as a major component and has
additives and electrolyte mixed therein. Typically, the electrolyte
includes potassium hydroxide (KOH) aqueous solution. When the hydration
ions are transferred to the zinc gel 16, the zinc powder is oxidized
through a reaction with the hydration ions. This reaction can be
represented by the following Chemical Formula.
[0010]ChemistryFigure 2
Zn+2OH-Zn(OH)2+2e.sup.
Zn+2OH-ZnO+H2O+2e- [Chem. 2]
[0011]Electrons are generated in the cathode through this reaction, and
the generated electrons are transferred through the cathode can 20.
Through this chemical reaction, voltage of a maximum of 1.65V can be
generated theoretically.
[0012]This zinc-air cell has advantageous properties in terms of voltage,
the energy density, the discharge capacity, a discharge characteristic,
etc. However, use of the conventional zinc-air cell is limited to special
fields such as hearing aids and cameras. In particular, sealing using the
anode can 18 and the cathode can 20 for transferring electrons, generated
from the cathode, to the anode is indispensable. Thus, the conventional
zinc-air cell has been only sold as a button shape cell, but has not been
fabricated as a shape that can be used for mobile terminal or cellular
phone battery, preferably, a rectangular parallelepiped shape.
[0013]Therefore, there is a need for a method of fabricating the zinc-air
cell, having the above advantageous properties, in a shape that can be
used for cellular phone battery, etc. That is, it is necessary to develop
a method of obviating sealing using the anode can 18 and the cathode can
20, that is, the problem which was indispensable to transfer electrons
between the anode and the cathode, but made the conventional zinc-air
cell fabricated only in the button shape.
DISCLOSURE OF INVENTION
Technical Problem
[0014]Accordingly, the present invention has been made in view of the
above problems occurring in the prior art, and an object of the present
invention is to provide a method of fabricating a zinc-air cell in a
shape that can be used in a cellular phone battery, etc., and a zinc-air
cell fabricated using the method, in which, in the zinc-air cell, a film
adapted to function as the anode is stacked on a cup adapted to function
as a sealant and a zinc gel adapted to function as the cathode is filled
between the cup and the film, thus efficiently sealing the zinc-air cell,
and a terminal is used as an electron migration path, thereby obviating
sealing using the anode can 18 and the cathode can 20 when fabricating
the zinc-air cell.
Technical Solution
[0015]To achieve the above object, in accordance with an embodiment of the
present invention, there is provided a zinc-air cell, including a cup
adapted to function as a sealant of the cell, a film adapted to function
as an anode of the cell and bonded on the cup, wherein the film has a
first surface with a hydrophobic property and a second surface with ion
permeability, and the second surface comes in contact with the cup, and a
zinc gel adapted to function as a cathode of the cell and filled between
the cup and the sealant.
[0016]Preferably, the zinc-air cell can further include a cathode terminal
drawn from the zinc gel to the outside of the cell and transporting
electrons, which are generated by a chemical reaction in the zinc gel,
and an anode terminal for supplying electrons from the outside to the
film such that a chemical reaction can be generated in the film adapted
to function as the anode.
[0017]Here, the first surface is preferably formed from Teflon material,
and the second surface is formed of polypropylene material.
[0018]Further, the cup is preferably formed from polypropylene material.
[0019]Meanwhile, the cup can be preferably formed from the same material
as that of the second surface of the film.
[0020]The film can have a multi-layered structure including a metal mesh,
and the anode terminal can be formed by removing a layer on a top of the
metal mesh in one end of the film and exposing the metal mesh.
[0021]Further, preferably, the cathode terminal has a shape curved in an S
shape or C shape.
[0022]To achieve the above object, in accordance with an embodiment of the
present invention, there is provided a method of fabricating a zinc-air
cell, including the steps of preparing a cup having a central portion of
a downward depressed shape and functioning as a sealant of the cell,
bonding a film adapted to function as an anode of the cell on the cup,
wherein the film has a first surface with a hydrophobic property and a
second surface with ion permeability, and the second surface comes in
contact with the cup, and filling a zinc gel, which functions as a
cathode of the cell, in a space between the cup and the sealant.
[0023]Preferably, the method further includes the steps of inserting a
cathode terminal for carrying electrons, which are generated in the zinc
gel, into the zinc gel and drawing the cathode terminal outside the cell,
and forming an anode terminal for supplying electrons to the film.
[0024]Preferably, the step of forming the anode terminal includes removing
a layer on a top of the metal mesh in one end of the film and exposing
the metal mesh.
[0026]Meanwhile, the method can further include the step of curving edges
of the cup in a shape that can surround the film so that the film is
depressed in the edges of the cup.
[0027]Here, the cup is formed of the same material as that of the second
surface of the film.
[0028]Further, preferably, the method further includes the step of curving
the cathode terminal in an S shape or C shape.
ADVANTAGEOUS EFFECTS
[0029]In accordance with the present invention, a zinc-air cell can be
implemented in a desired shape, for example, a rectangular parallelepiped
shape applicable to a cellular phone battery.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030]Further objects and advantages of the invention can be more fully
understood from the following detailed description taken in conjunction
with the accompanying drawings in which:
[0031]FIG. 1 is a sectional view of a conventional button shape zinc-air
cell;
[0032]FIG. 2 is a sectional view of a zinc-air cell in accordance with an
embodiment of the present invention;
[0033]FIG. 3 is a sectional view of a zinc-air cell in accordance with
another embodiment of the present invention;
[0034]FIG. 4 is a sectional view of a film adapted to function as the
anode of the zinc-air cell; and
[0035]FIG. 5 is a perspective view of the zinc-air cell in accordance with
the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0036]The present invention will now be described in detail in connection
with an embodiment with reference to the accompanying drawings.
[0037]FIG. 2 is a sectional view of a zinc-air cell in accordance with an
embodiment of the present invention. The zinc-air cell includes a cup 22
functioning as a sealant, a film 20 which is fused or bonded on the cup
22 and functions an air anode generating the reaction of the Chemical
Formula 1, and a zinc gel 26 which is filled between the cup 22 and the
film 20 and functions as a cathode generating the reaction of the
Chemical Formula 2.
[0038]The cup 22 has a central portion of a downward depressed shape or a
rectangle plate shape. The depressed degree of the cup 22 can be properly
controlled in consideration of the amount of the zinc gel 26 filled
between the cup 22 and the film 20.
[0039]The zinc-air cell further includes a cathode terminal 24 drawn from
the zinc gel 26 to the outside of the cell, and an anode terminal 25
extending from the film 20. The film 20 is fabricated in a shape that can
form the anode terminal 25 as shown in FIGS. 2 and 5, and the anode
terminal 25 is described later on. The cathode terminal 24 transports
electrons, which are generated by the reaction of the Chemical Formula 2,
from a portion in which the zinc gel 26 is filled to the outside of the
cell, and the anode terminal transports electrons from the outside of the
cell to the film 20 so that the reaction of the Chemical Formula 1 is
generated in the film 20. In the zinc-air cell, typically, the zinc gel
26 cannot be fully filled in space between the cup 22 and the film 20.
For this reason, there is a possibility that the cathode terminal 24 may
not come in touch with the zinc gel 26 having fluidity. Therefore, it is
preferred that the cathode terminal 24 inserted into the zinc-air cell be
curved in an S shape or C shape and always come in contact with the zinc
gel 26 irrespective of which state is the zinc gel 26 with fluidity is
placed.
[0040]In the zinc-air cell in accordance with the present invention, the
film 20 functioning as the anode employs a film as shown in FIG. 4. The
anode film includes a separator 350 for separating the zinc gel 300 from
other elements, a catalyst layer 330 that generates the reaction of the
Chemical Formula 1 through a reaction with oxygen in the air, a metal
mesh 320, and a hydrophobic membrane 310 disposed to extend the lifespan
of the cell by preventing adsorption of carbon dioxide. The catalyst
layer 330 and the separator 350 are bonded together by a bonding agent
340. In general, the separator 350 employs material having ion
permeability, for example, polypropylene material, and the hydrophobic
membrane 310 employs Teflon material. Further, the catalyst layer 330 is
generally carbon material.
[0041]In the film shown in FIG. 4, the hydrophobic membrane 310 is very
difficult to adhere to other materials due to an inert characteristic,
whereas the separator 350 has a characteristic that it can easily adhere
to other materials. Thus, if the separator 350 of the film 20 is brought
in contact with the cup 22 as shown in FIG. 2 using this characteristic,
the bonding effect can be increased. The bonding method may employ heat
fusion, ultrasonic fusion or a bonding method. This cup 22 can use the
same material as that of the separator 350, that is, polypropylene, but
not limited thereto. For example, the cup 22 can employ polymer material,
such as plastic or resin, which is appropriate for sealing in
consideration of material of the separator 350.
[0042]Further, in the film shown in FIG. 4, the metal mesh 320 is a
conductive material and can become a migration path of electrons that are
generated by a chemical reaction occurring in the film 20. Therefore, in
one end of the film 20 fabricated to have a proper shape so that the
anode terminal 25 can be formed as shown in FIGS. 2 and 4, the
hydrophobic membrane 310 is removed so as to expose the metal mesh 320.
Thus, the exposed metal mesh 320 can be utilized as the anode terminal
25.
[0043]Meanwhile, the zinc-air cell can further include a casing (not
shown) to surround the cup 22 and the film 20 formed on the cup 22. In
this case, apertures for passing the air have to be formed in the casing
in order for the film 20 to come in contact with the air and therefore
generate the chemical reaction of the Chemical Formula 1. Further, the
casing has to be formed such that the cathode terminal 24 and the anode
terminal 25 are drawn to the outside.
[0044]Next, the zinc-air cell in accordance with another embodiment of the
present invention is described with reference to FIG. 3. In the zinc-air
cell, the edges of the cup 22 are formed wide enough to surround the film
20. This configuration further enhances adhesive force between the cup 22
and the film. In the zinc-air cell shown in FIG. 3, the entire
configurations other than the shape of the cup 22 are substantially the
same as that of an embodiment of the present invention, which has been
described with reference to FIG. 2, and description thereof is omitted.
Further, although it is shown in FIG. 3 that the cup 22 is formed to
surround the film 20, the area of the film 20 may be formed greater than
the plan area of the cup 22 such that the edges of the film 20 are curved
and surround the cup 22.
[0045]As described above, in the zinc-air cell in accordance with the
present invention, the film 20 is stacked on the rectangle plate-shaped
cup 22 having the downward depressed central portion. Accordingly, the
zinc-air cell can be fully sealed, thereby realizing efficient and
convenient sealing. The conventional zinc-air cell could be fabricated in
a specific shape due to the difficulty of sealing. However, the present
invention has solved the difficulty of such sealing and therefore enables
fabrication of a zinc-air cell having a desired shape.
[0046]Meanwhile, the zinc-air cell in accordance with the present
invention employs the cathode terminal 24 and the anode terminal 25 as an
electron migration path required for a chemical reaction in the anode and
the cathode. Thus, the present invention excludes the anode can 18 and
the cathode can 20, which were used as the electron migration path in the
conventional zinc-air cell, so that an overall shape of the cell can be
implemented as a rectangular parallelepiped shape applicable to a
cellular phone battery.
[0047]A method of fabricating the zinc-air cell in accordance with an
embodiment of the present invention is described below with reference to
FIG. 2. First, the cup 22 functioning as the sealant of the zinc-air cell
is prepared. The cup 22 can have a shape whose central portion is
depressed or a rectangle plate shape. In this case, the zinc gel 26
functioning as the cathode of the cell will be filled in the downward
depressed portion of the cup 22 and, therefore, the cup 22 is formed in
consideration of the amount of the zinc gel 26 to be filled.
[0048]Next, the zinc gel 26 functioning as the cathode of the cell is
filled in the downward depressed portion of the cup 22. The amount of the
zinc gel 26 is controlled in such a way not to fully fill space created
when the film 20 is bonded on the cup 22.
[0049]The cathode terminal 24 is then inserted into the zinc gel 26, and
the film 20 is bonded on the cup 22. At this time, the hydrophobic
membrane 310 (refer to FIG. 4) of the film 20 is placed on the upper side
and the separator 350 is placed on the lower side, that is, a position
coming in contact with the cup 22, and the cathode terminal 24 is drawn
from the zinc gel 26 to the outside through the contact portion of the
cup 22 and the film 20. Further, in order to remove a possibility that
the cathode terminal 24 may not come in contact with the zinc gel 26 with
fluidity as described above, the cathode terminal 24 is preferably curved
in an S shape or C shape. A bonding method using heat fusion, ultrasonic
fusion or a bonding agent can be used in order to adhere the cup 22 and
the separator 350 of the film 20 together. Material of the cup 22 may be
the same as that of the separator 350 placed on the lower side of the
film 20, but not limited thereto. For example, it is preferred that the
material of the cup 22 be material that can be easily bonded in
consideration of material of the separator 350. If polymer material such
as polypropylene is used, a sealing effect can be further increased due
to heat or ultrasonic fusion.
[0050]More specifically, heat fusion is a method of performing bonding by
heating the cup 22 using a heater. Further, fusion using ultrasonic waves
is a method of fabricating a jig of a proper shape in order to fix the
cup 22 and the film 20 and performing fusion using an ultrasonic fusion
apparatus. Meanwhile, the bonding method using a bonding agent is a
method of coating a bonding agent on the edges of the cup 22, that is, a
portion that will be bonded with the film 20 and then adhering the film
20. An adhesive tape may be used instead of the bonding agent.
[0051]In the bonding of the cup 22 and the film 20, a variety of bonding
methods other than the above methods can be used, and it is considered
that those having ordinary skill in the art may select a known bonding
method and apply the selected method to the present invention.
[0052]Meanwhile, in the case in which the edges of the cup 22 are wide as
shown in FIG. 3 in fabricating the zinc-air cell, a process of curving
the edges of the cup 22 so that the film 20 is depressed may be further
performed. If this process is performed additionally, bonding force
between the film 20 and the cup 22 can be further improved. Further,
although it is shown in FIG. 3 that the cup 22 surrounds the film 20, the
area of the film 20 may be formed greater than the plan area of the cup
22 such that the edges of the film 20 are curved and surround the cup 22.
[0053]As described above, in the fabrication of the zinc-air cell in
accordance with the present invention, the film 20 is only stacked on the
rectangle plate-shaped cup 22 having the downward depressed central
portion, hereby realizing convenient and full sealing. Accordingly, the
present invention can fabricate a zinc-air cell having a desired shape by
solving the conventional problem in which a cell could be fabricated in a
specific shape due to the difficulty of sealing.
[0054]Next, for the purpose of a chemical reaction in the film 20, the
anode terminal 25 for supplying electrons is formed. The anode terminal
25 is formed by peeling off the hydrophobic membrane 310 at one end of
the film 20, which will be used as the anode terminal, and exposing the
metal mesh 320. The cathode terminal 24 and the anode terminal 25 can be
drawn outside the casing (not shown) of a zinc-air cell to be formed
later on.
[0055]As described above, the cathode terminal 24 and the anode terminal
25 are used as an electron migration path required for a chemical
reaction in the anode and the cathode. Accordingly, the use of the anode
can 18 and the cathode can 20 can be obviated, so that a zinc-air cell
can be implemented as a desired shape, more specifically, a rectangular
parallelepiped shape that is applicable to a cellular phone battery.
[0056]Although detailed embodiments of the present invention have been
described, they are only illustrative. For example, in this
specification, the zinc-air cell of the rectangular parallelepiped shape
and the fabrication method of the cell have been disclosed. However, the
shape of the cell is not limited to the above examples, and those having
ordinary skill in the art can easily fabricate the cell of a desired
shape by employing the present invention. Further, the materials of the
respective constituent elements described in this specification can be
easily selected from various known materials and replaced by those having
ordinary skill in the art. Further, those having ordinary skill in the
art may omit some of the constituent elements described in this
specification without degrading performance or add a constituent
element(s) in order to improve the performance. In addition, those having
ordinary skill in the art may change the sequence of the method steps
described in this specification according to process environment or
equipment. Therefore, it is to be understood that the scope of the
invention should be decided by the appended claims and equivalent
arrangements not the embodiments.
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As Spanish and Portuguese settlers gradually converted many of the natives of their far-flung colonies, Christian iconography had a major impact on the art of these regions in the 17th through 19th ...(Read More)
This monumental photographic tribute celebrates the beautiful and incredibly diverse South American continent and its neighboring islands in all their color and gaiety. Olivier Föllmi traveled
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Mexican-born journalist Alma Guillermoprieto has reported widely on the political situation in Latin America. Her first book, however, was this fascinating 1990 exploration of the world of samba ...(Read More)
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A couple of weeks ago, I wrote a blog saying that I wasn't going to freak out anymore if my kids use an occasional swear word, as long as they were not using it to name call, i.e. hurt someone's feelings. Many talkbackers criticized my judgment as a parent for this decision. Well, folks, this blog's for you.
Perhaps this incident was my karmic payback for decriminalizing cussing in my household. Perhaps not. Either way, last week we went to Beans & Barley for dinner, and my 4-year-old, who has never dropped an F-bomb in his life, looked at the server and said in a very loud, clear voice that he wanted a "banana f---ing smoothie."
I was shocked, mortified and a little amused all at the same time. After my husband apologized to the server, we told our son that he should not use that word in public because it could hurt some peoples' feelings. He seemed to understand.
Most parents have an example of this kind of thing. I'm sharing mine to say that, despite my philosophical thoughts on kids and swearing, it's still embarassing. But it's a little humorous, too.
That night, my husband said right before I drifted off to sleep, "Today will always go down for me as the day Brett Favre retired from football and Levi ordered a banana f---ing smoothie."
Talkbacks
4yrs old... Wow! Why don't you let him brush up on his swearing and encourage him to watch all the "Sopranos" episodes from 1-end. How about having him see George Carlin's "7 words you can't say on T.V." Or maybe while instilling fundamentals of early childhood development, teach him the colors of the rainbow - "ROY-G-F___ing-BIV". I'm sure his incoming KINDERGARDEN class (and teacher) will be impressed with that knowlege!
dpk- fascinating commentary on racial codes and blah, blah, blah! However, I think she said the kid was 4? I'm not sure this will determine his social failure or success at this point. Sounds like someone is an "uptight twit," but who could that be....
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http://onmilwaukee.com/myOMC/authors/mollysnyder/swearingkids2.html
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A&A Marketing Group is a Marketing Firm located in the heart of Dallas, TX. that specializes in business development, marketing, sales and fundraising for a large number of Fortune 100 and World-renow
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CarGurus Quick Poll
2002 Toyota Tundra 4 Dr SR5 V8 4WD Extended Cab SB Review
by Matt
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Best Practices in School Psychology,7th Ed (Digital)
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Update your library of professional resources with the new edition of Best Practices in School Psychology, 7th edition. Following the framework for the 2020 NASP Practice Model, this foundational series covers the most valued information in school psychology. With an expanded focus on social justice and multitiered, evidence-based approaches, Best Practices is essential for practitioners, graduate students, and faculty.
Receive digital access to all three volumes for the life of the edition
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2015 Golden Globe Nominations: Complete List of Nominees
ByMovienewzLast updated onAugust 15, 2015
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The nominations for the 72nd Golden Globe Awards were announced bright and early this morning at the Beverly Hilton hotel. During the traditional pre-dawn ceremony in Beverly Hills, HFPA president Theo Kingma introduced Kate Beckinsale, two-time Golden Globe Award-nominee Peter Krause, Paula Patton, and Golden Globe-winner and five-time nominee Jeremy Piven did the honors. The 72nd Annual Golden Globe Awards, hosted by Tina Fey and Amy Poehler, will air on Sunday, January 11, 2015, LIVE coast-to-coast on NBC from 5:00-8:00 p.m. (PST)/8:00-11:00 p.m. (EST).
[ad name="468×60-text-ad"] Director Christopher Nolan has cast Matthew McConaughey as the male lead in his mysterious sci-fi thriller Interstellar, based on a script by Jonathan Nolan (The Dark Knight Rises)….
Dimension Films and Blumhouse Productions' long-in-development horror remake, Amityville is now titled Amityville: The Awakening. The project was originally titled The Amityville Horror: The Lost Tapes. In Amityville: The Awakening,…
[ad name="468×60-text-ad"] Film director and long-time Denzel Washington collaborator Tony Scott died Sunday at the age of 68 in an apparent suicide. The British-born Scott, who lived in Beverly Hills,…
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10 VR Horror Games to Play This Halloween
The Entire VR Industry in One Little Email
The Daily Roundup is our comprehensive coverage of the VR industry wrapped up into one daily email, delivered directly to your inbox.
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It's that time of the year again, when you bring out the big bag of candy, put on your spookiest outfit, and turn off the lights and pretend no one's home. It's Halloween!
And to celebrate, we rounded up 10 of our favorite VR games which span a number of horror and thriller sub-genres.
Coincidentally, most of the games below support SteamVR-compatible headsets and PSVR. If you're looking for Quest titles, skip to the bottom section for a few choice suggestions.
Red Matter
Take one part Soviet brutalism, two parts puzzle-adventure, mix them up in the low atmosphere of a mysteriously abandoned off-world colony, and garnish with a slice of Cold War espionage. That's the sci-fi thriller Red Matter (2018) in a nutshell. You'll find it on all major VR headsets, but the Quest port is by far the most impressive technically speaking, as Vertical Robot has managed to squeeze in an incredible amount of detail on the mobile platform.
Five Nights at Freddy's VR: Help Wanted
The makers of the famous jump scare-tastic Five Nights at Freddy's, Steel Wool Studios, have done the unthinkable and made a version for most of the major VR headsets (excluding Quest). There's also some fresh DLC if you're looking for more reasons to soil yourself.
Resident Evil 7 biohazard (PSVR)
If you own a PSVR, you might look no further than Capcom's Resident Evil 7 biohazard (2017), one of the best VR adaptations on the PlayStation Store currently. Sorry folks, but the version on Steam still doesn't have VR support, so PSVR only for now
The Forest
Released via Early Access for PC back in 2014, the horror-survival game The Forest (2018) wasn't supposed to be a VR game, but developing studio Endnight Games have tossed in some pretty serviceable VR support. You can build, fend off cannibals, and play the entire game in VR, including multiplayer. Yes, there's a PS4 version. No, it doesn't have PSVR support.
Transference
Ubisoft and Elijah Wood's production company SpectreVision got together to make this chilling psychological thriller in 2018. The demented, ever-changing house hides some pretty challenging themes inside.
A Chair in a Room: Greenwater
It's an oft overlooked oldie (relatively speaking, it's from 2016), but it's still a goodie. A Chair in a Room (2016) from Wolf & Wood Interactive is more of a puzzle game with some horror elements to it than a pure horror game as such, but it still has plenty of creepy atmosphere to sop up on the spookiest of holidays.
Duck Season
Stress Level Zero's Duck Season (2017) is a bit of a mix between '80s nostalgia and twisted horror; the contrasts here between fun and happy memories and dark imagination of you, a kid at home trying to play the Duck Hunt-inspired game-within-a-game, borders on the schizophrenic. Truly unsettling.
In Death
Sólfar Studios' rogue-lite bow-shooter is drenched in gothic horror. You fruitlessly battle against increasingly powerful monsters with your trusty bow, all in service of an achievement-based progression system that advances between sessions, revealing yet more unseen horrors.
What about Quest games?
The number of titles available on Quest currently pales in comparison to what you can find on the other, more established VR platforms. That said, there are a few spooky titles worth checking out (besides Red Matter, that is):
Dreadhalls – An oldie in the mobile VR realm, but still extremely capable of putting you on edge as you race down dank dungeon corridors from ghastly horrors in search of a way out.
The Exorcist: Legion VR – A multi-chapter horror-adventure that teaches you about the value of friendship. Just kidding. It's all about ghosts and exorcism and shit.
I'm sure I read months ago that they weren't planning on a PC VR release, such a shame. Still not bought or played it yet, until they do. Even though it's pretty cheap nowadays.
ivan
I also intrested. It was timed exclusive as was announced…
bakterius
I buyed RE7 long ago and still not play.. 1 year exclusivity wanish bu stupid namco politics not want release already VR ready game to PC. I try play with Vorpx but its not too good….. I not buy for 1 interrresting game useles console (for me).
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Alfa Romeo/Audi
Mattia Binotto
After deciding to depart Ferrari on the finish of November, Mattia Binotto is more likely to be on almost each workforce's shortlist.
Binotto's wide selection of expertise will attraction tremendously to the Audi group as a result of they are going to be manufacturing their very own energy unit from 2026.
The Italian performed a key function in Ferrari's energy unit division earlier than taking up as technical director in 2016.
As technical director, Ferrari returned to kind in 2017 with an progressive, thrilling package deal, which solely misplaced out to Mercedes resulting from their superior energy unit.
Binotto could be an astute signing given his wealth of expertise in Ferrari's engine division, mixed together with his latest expertise in managing the workforce as an entire.
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The undertaking might additionally attraction to Binotto as a result of the workforce relies in Switzerland, the nation of his delivery.
Jost Capito
Following his shock departure from Williams, Capito might swap to Alfa Romeo.
The 64-year-old's finest years in administration got here throughout his time with Volkswagen, dominating the World Rally Championship with a hat-trick of titles.
Given his prior relationship to the Volkswagen group, which Audi are a part of, it will be a smart match.
Capito did come out of retirement to work with Williams, so maybe he doesn't wish to lengthen his working profession even additional with the workforce principal function at Alfa Romeo.
Allan McNish
Allan McNish has been related to Audi for almost all of his racing profession.
From his days in sportscars, to operating their Method E workforce, McNish is an Audi man by way of and thru.
Whereas Audi's affect on the workforce isn't too vital in the meanwhile, given they're nonetheless often called Alfa Romeo, they'll be wanting to place their very own folks in place forward of 2026 like they've finished with Seidl.
McNish could be a logical alternative due to his lengthy affiliation with the German model, his prior expertise in Method E as a workforce boss.
Beat Zehnder
A stalwart of the Sauber firm, Beat Zehnder has been a part of the Swiss outfit because it began in 1993.
Beginning off as a mechanic, he rapidly moved up the ranks within the Nineties.
By 1995 he grew to become workforce supervisor, or sporting director, as he's nonetheless often called now.
Zehnder's wealth of expertise and being embedded within the Hinwil workforce makes him the right candidate.
It's possible Audi will need their very own candidate within the function, however Zehnder could be the right stop-gap till then.
What about Williams?
Capito and Demaison's departures from Grove caught everybody off guard.
It's nonetheless unclear whether or not it was their very own choice or the proprietor's – Dorilton Capital – who could have grown pissed off by Williams' lack of progress in 2022.
Regardless, there are only a few apparent candidates to exchange Capito.
One identify that springs to thoughts is Susie Wolff.
Wolff spent numerous years at Williams as their take a look at and reserve driver, collaborating in numerous FP1 classes between 2014 and 2015.
Since then, she has held roles as workforce principal of the Venturi Method E workforce, guiding the workforce to P2 within the drivers' championship with Edo Mortara.
Wolff moved to a CEO place after the 2020-21 Method E season earlier than leaving the workforce following Maserati's takeover.
Her expertise in each F1 and administration roles makes her an appropriate candidate.
Whether or not she'd wish to commit her time to 24 races on the street is one other query.
Mercedes boss Toto Wolff has already admitted that he'll "skip a couple of races" throughout F1's record-breaking 23-race season in an effort to "survive
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About
Our Outer Banks Law Firm
Simmons Law was founded by Chrissy Simmons in 2013.
Chrissy opened her private practice initially concentrating in the areas of family law and criminal defense. Over the years, the firm's practice areas have expanded into juvenile court, DSS Court, and all aspects of domestic violence.
Meet Chrissy Simmons
Lead Attorney & Founder
Chrissy Simmons grew up in the suburbs of Atlanta, GA; however, her immediate and extended family have called the OBX home for over 50 years.
Education
In 1999, Chrissy graduated Summa Cum Laude with a Bachelor of Arts in Criminal Justice from Old Dominion University. She received her Juris Doctor from Wake Forest School of Law in 2003 and began her legal career as an Assistant District Attorney in the First Judicial District. As a prosecutor, Chrissy handled all levels of misdemeanor and felony cases in Juvenile, District, and Superior Courts.
PROFESSIONAL + COMMUNITY
Memberships:
North Carolina State Bar
The North Carolina Bar Association
The First Judicial District Bar
The Dare County Bar
Current or Past Board Member on:
The Outer Banks Relief Foundation
Dare Coalition Against Substance Abuse
YMCA Advisory Board
Dare Teen Court
The Simmons family directs and sponsors the annual OBX Four Corners Basketball Camp and has done so for over 20 years. Chrissy and her family are faithful members of Kitty Hawk United Methodist Church. Chrissy and her husband live in Manteo with their two sons.
When not in the office, Chrissy enjoys exercising, relaxing on the beach while her kids surf and skim, camping with her son and his Scout troop, and she most often can be found at the various sporting complexes throughout the region cheering on her children and their teams in baseball, basketball and soccer.
Amie Ballance
Legal Assistant
Amie is a long-time resident of Dare and Currituck County. She has worked for over ten (10) years in the legal field including as a legal assistant at Vandeventer Black, PLLC, a victim witness coordinator for the District Attorney's Office of the First Judicial District and a case manager for North Carolina Child Support Enforcement Agency.
Chrissy and Amie worked together while both were in the DA's office and Chrissy knew that Amie was the right fit for her growing practice. Amie is the face of Simmons Law Firm and will greet you with courtesy, respect, and thoroughness when you call or come to the office.
When not assisting clients at Simmons Law, Amie can usually be found at a softball field somewhere in eastern North Carolina faithfully supporting her two daughters. Amie and her family reside in Wanchese and are active members of the Wanchese Assembly of God.
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A Guide To Finding Love In Vancouver With Out Utilizing Dating Apps
Please observe that the website does have a selection of additional features in comparison with the app . Members can spruce up their profiles with catchy headlines, brief essays about themselves and the matches they're on the lookout for, and a video introduction. Other optional essay questions provide additional perception into a member's character, pertaining to topics like first date concepts, travel plans, hobbies, and favourite jokes. Acclaimed Vancouver pubs like Manchester Public Eatery, the Lamplighter and Colonyhost themed trivia sport nights with prizes and drink discounts. While these trivia nights aren't particularly catered in the direction of singles, it's an ideal alternative to satisfy and socialize with individuals who share your love for The Office or the cinematic triumphs of Vin Diesel.
Be wary of all unsolicited messages—If you obtain spam, don't reply or click on hyperlinks inside the message. "I would caution individuals be very cautious investing in Crypto, these rip-off web sites seem legit. Don't take the advice of 1 one that you have met on-line and never in real life. If investing in a dealer, verify that the enterprise dealer is registered with the Alberta Securities Commission first," said Cst. Now that you've got a greater idea of the variables that lead to interpersonal attraction and that are important in shut relationships, you must be getting a reasonably good idea of the things that partners have to do to help them keep collectively.
Send customized messages somewhat than generic one-liners. And reply within a reasonable time – analysis means that enjoying hard to get doesn't work. Stanger insists that you must download a number of dating apps to provide yourself the most effective chance at finding the best particular person for you.
Look for a dating website that offers simplicity, comfort, and ease of use.
The fourth cell within the table, lower right, represents the avoidant-fearful style, which describes people who are not meeting goals of either self-concern or other-concern.
Less ghosting, more connections and other reasons to be optimistic about in search of love in these occasions. AskMen may receives a commission should you click on a link on this article and buy a product or service. At EliteSingles, we believe everybody deserves love, and we'll endeavour that can help you discover it wherever you are in the world! Away from messaging, you'll be ready to verify who considered your profile and even add members to favorites for simpler communication within the event that they tickle your fancy. Also, you probably can take the sting off beginning conversations by sending winks and flirts to specific curiosity without having to say a word.
How A Professional Matchmaker Succeeded Where Dating Web Sites Failed
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MillionaireMatch has been in business for 20 years , bringing together lots of of thousands of profitable singles and their admirers. The site has been featured on CNN, ABC, CBS, and in publications like The Wall Street Journal. Thanks to the reputation it's earned for offering a excessive caliber experience, MillioinaireMatch now has over 5.2 million members who have 2 million plus monthly conversations. This singles networking group is for anyone who is attention-grabbing in meeting others by way of wine tastings, social dinners and pub nights. Members sometimes publish open invites to imminent concerts and parties on the group's on-line message board. If you are into low strain meet-ups, this may be the group for you.
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Archives
Archives
China 20 years later
Sorry to break my blog break yet again, but today is 20 years after the Tiananmen Square massacre, and I can remember being glued to the TV and mourning.
We can't really blame the young Chinese for their apolitical materialism, can we? Is anyone here thinking about next year, let alone 20 or 40 years down the road? Is anyone thinking at all? The banks and the old industries are using up all of the social democratic resources we need to "buy" democracy, while the middle class scrambles for cover …
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6 Negotiation Techniques with Vendors (Get the Best Deal)
'Are we good negotiators?' This can be a baffling question. If it ever came up, what would our answer be? Most likely, few of us would answer 'Yes!' Why? To many, a person who has mastered negotiation techniques with vendors is a genius, somebody from outside our world; an extraterrestrial perhaps.
No wonder, we only hear of such terms during those rare adrenaline-raising moments, coming with closely- related terms like 'prisoners held hostage,' 'release of hostages' and 'seasoned negotiator.' It, therefore, seems like we require special skills to become 'skilled negotiators'.
A seller attending to a customer
Achieving Successful Negotiation with Vendors
1. Seasoned negotiator
Yet, is this true? Does the art of negotiation require special skills that only 'seasoned diplomats' are endowed with? Think about it: We all have to negotiate every day, one way or another. It could be that we are negotiating for a deal that is necessary for our good or on behalf of others.
Depending on situations, it might even start right there at the local grocery store, when we need to purchase some daily supplies. Or we might be store owners who need to deal with vendors daily to get needed supplies. Yes, indeed, we all have to negotiate every day! As you will discover, no special skills are necessary to rival some imaginary 'seasoned negotiator.'
Ideally, the art of negotiation should not be difficult. We only need plain common sense to hit the ground running! With just a little practice, negotiation can become a highly enjoyable experience that rakes in huge savings and brings tremendous benefits. It might be that we only lack the techniques and confidence to carry out a successful negotiation with vendors. It means we are self-limiting and need to learn a few tips.
2. No confrontation
To become an effective negotiator, there are a few fundamental principles that we can learn and apply. The results will surprise us. We don't have to adopt any particular approach or style to succeed as negotiators. Indeed, negotiation is a process that often begins at the time we first engage with our vendor. We must do it well to get the best deal! Keep in mind that if we ever had the opportunity to interact with a vendor, this is the chance to lay a proper groundwork and negotiate for that perfect deal that leaves us with some good change in the pocket.
Must we become confrontational to succeed as negotiators? Of course, we have all heard about assertiveness and aggressiveness as a successful life- skill. Happily, to succeed, we don't need to be super-aggressive, in the confrontational sense of the word. On the contrary, recent research shows that 99% of the time this is precisely what we must avoid getting good results in negotiating. Avoid being confrontational!
If we own a store or business and must negotiate with vendors every day, how can we use these tips to negotiate with a supplier and ensure we get the best deal? Here is what we need to do:
People preparing assorted meals and beverages
3. Mutual goals
As noted, the first thing to remember is that we don't have to be confrontational or adversarial to have our way with vendors. We don't need to do that in pursuit of the much sought-after deal. No. Instead, parties engaging in a negotiation should start from the perspective that they are mere collaborators who are seeking a mutually acceptable goal.
This means that collaboration is what should carry the day. If we have reached the negotiation point with a potential vendor, it means that both of these parties believe it is possible to reach a deal, and that both will gain some benefit at the end of the process. We should, therefore, approach the talks with a positive mindset premised on the fact that we are working together towards a common goal. If we start the negotiation with the vendors from this progressive attitude and techniques, the chances are that this process will be successful and that we will get a deal.
4. Demotivation
We must work to guarantee that the potential contract is mutually agreeable. This is crucial. For instance, is there any benefit in trying to press a potential vendor to agree to unusual terms that are also unfavorable for them? What could be the long term effects of this kind of approach? This attitude can lead to resentment and demotivation on the part of the vendor. It would be especially damaging to us if they have other clients who are more agreeable. Ultimately, we could lose out on the desired deal!
People in a caffeteria
6 Powerful Negotiation Techniques to Win the Best Deals with Vendors
1. Bond
From the outset, we must be friendly to our valued vendors. Why? Studies have shown that the initial moments of the discussion are crucial. Indeed, the first five minutes of the talks can determine whether the process will succeed or fail. We must go ahead and predict matters. We should remember to start the process in a friendly way. Our goal is to establish some common ground with the vendor. We know that we won't maintain this stance throughout, but it is the best approach in the initial stages when the process is just beginning. In most cases, it can work wonders to be friendly with our vendor.
2. Network
We must approach the 'table' armed with all the necessary facts. Before the negotiation, we should do some strategic background check, so we are well prepared. Indeed, we cannot afford to allow the vendor to upstage us with sudden surprises, just because we failed to carry out our homework well. We must use our networks. What kind of deals and rates did they have with the vendor? We will cleverly use this information to gain a fair advantage over our vendor.
3. Mapping
Do we know what our vendor wants? If we do, we have a better chance of winning the deal with them. We need to determine exactly what drives them in their business. Find out: Does this particular vendor target to make a quick sale so that he meets the set quota for the day? Is he, instead, targeting the profit margin? Is he price-sensitive? If we know a thing or two about this, we are well-armed. Chances are: we will win big.
People tossing assorted beverages
4. Keep friends
Is this the kind of person that we will have to work with in the long haul? Do we have to work closely with him for the success of our business? If we answer 'Yes' to this, we need to start getting cordial and maintain the tempo. It matters a great deal. Is this, perhaps, a one-off vendor whom we will probably never meet again? We should go ahead and do what we must do. The key? We should know our game well, and act to keep friends whom we will need tomorrow.
5. Mixed-signal
We must learn the 'walk-away' trick. It can be powerful to walk away. If we show the vendor that it doesn't matter much if the deal fails, we will suddenly become powerful! If we make it clear, through our body language, that we have a plan B, that the deal is not a life and death matter, we will shift the pressure to cut the deal on the vendor. Indeed, we can step back, away from the table, several times if need be. This can be a sufficient signal to the vendor. He will detect that we can walk away from this deal and it won't hurt. He will be forced to think twice.
6. Trump card
From the word go, we must make it clear to the vendor that alternatives to the deal exist. Viable options. Make sure they get it right. If necessary, we will bombard them with the details. Does the competition offer a cheaper, better deal that we think the vendor is unaware of? Let them know that it is not just some idle threat. It is our job to make them believe that a genuinely decent option lies somewhere and that we can always get back to it. Make it real, sound, and convincing. It is our trump card!
A woman speaking to a person holding a plastic cup
Are You Ready to Negotiate Now?
Successful negotiation with a vendor does not necessarily require any special skills. To win a negotiation, we need to prepare well by mastering the techniques stated above and be alert to our needs and that of the vendors. Preparation is the key. It gives us confidence. We can anticipate what the vendor wants and be prepared for it.
Moreover, a successful negotiation is a give and take affair. If we approach talks from the best perspective, we will get positive results and achieve the desired aims at the end of the lengthy process. Remember also: We don't have to be confrontational or unduly aggressive. We only need to cultivate a reasonable understanding of the business at hand.
Yes, we can learn these six powerful negotiation tips to benefit ourselves and the vendors. After all, we are essentially mere collaborators in a potentially mutually beneficial engagement. We must use these successful negotiation tips to get the best deal for our business and surge ahead of the competition
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10.8.16 Responding by Design
We are thrilled to announce that we have partnered with Spire to promote their upcoming event: Responding by Design. Special guests panelists will be exploring the topic of what it means to be called a creative/designer/thinker!
GUEST SPEAKERS:
Alex Lauderdale UI/UX Designer | Google
Alex is a UI/UX Veteran who subscribes to the ideal that better products are made through design thinking. Rhyme and reason are instrumental to how products and brands should be developed, not just a focus on having a pretty face. Alex has designed many notable mobile websites and applications. He is currently a designer at Google and formerly served as the lead creative for the championing social platform, Gloo.
Tishia Que Creative Director | Good Paper
Tishia has been designing for top tier brands for over 12 years and has done her work in such notable design hubs as New York, San Francisco and Los Angeles. As the creative director for Good Paper, she has been instrumental in driving the products and designs that creates employment for women who have escaped sex trafficking in the Philippines and young adults orphaned by disease in Rwanda.
Brad Abare
Design Thinking | Personality
Brad is a creative thought leader who trades in ideas and how to tell the story of your brand. An experienced communications team leader, Brad also serves on the board for the Center for Church Communications, a resource for the many needs of the modern church's communication professionals. Brad has serves on the leadership for the Barna Group, the Foursquare Church and widely popular website, Church Marketing Sucks.
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5 Obvious Reasons to Have a Fashion Jewellery for Every Women
I am a freelance blogger and I usually write about fashion, beauty, and travel.
1. They Are Pocket Friendly
According to the old saying, "A woman can never have enough jewellery." A woman's jewellery collection is never complete. She is always on the lookout for new trends in fashion or jewellery. Do you also have your eye on the gorgeous necklace in gold that you saw in the showroom Or the earring that will match your dress perfectly but cost you your monthly salary? With a heavy heart, you decide to give up on the idea of purchasing and just be happy with what you have.
Fashion jewellery is here to play a part. Fashion jewellery can elevate an outfit without spending too much on the jewellery or the outfit. You can make an outfit more exciting by wearing it every time. It is easy to choose unique jewellery. You can find the perfect piece that matches your style.
2. They are Exciting
It can make boring outfits fun and interesting. It can elevate any mood or colour. You can add sparkle to a plain saree with big earrings or a necklace to a sweater dress. You don't want to look like a Christmas tree by over-accessorizing your outfit.
3. They are Versatile
Fashion Jewellery can create a completely new look by being paired with a different style of outfit or with different jewellery. With the same outfit, you can create new looks every day. For a fun look, add chunky bracelets and colourful earrings online. You can rock the office look with simple pendant sets or stud earrings. Fashion jewellery is magical. They make every outfit look different.
4. They Make a Statement
Fashion Jewellery is a way to express yourself in style. The accessory can make a statement. Fashion clothes are a way to express your style and preferences. Fashion jewellery allows you to express your emotions and moods. A piece of bright and cheerful jewellery can express happiness, while a piece with minimal and more serious jewellery can express calmness. Fashion jewellery allows for creativity and individualism.
5. They are Game Changer
There are many styles, colours, patterns, and designs available in fashion jewellery. With a unique set of jewellery, you can make a statement in crowded places. People will compliment you and ask where they got the jewellery. This can spark conversation. You might also want to make friends with prominent guests at parties, so complimenting their jewellery will be a great way to break the ice.
Fashion jewellery is just as important as any clothing piece. Because Bollywood & Silver Screen has influenced Indian fashion jewellery, Imitation Jewellery is as elegant as any other precious or gold jewellery. Fashion Jewellery is a great option if you are looking to purchase a few pieces of jewellery for upcoming events.
People don't really care about whether you wear fashion jewellery or not. As long as it's worn with pride and elegance, today's world doesn't care. It's easy to shop online for Fashion Jewellery and browse a wide selection of jewellery.
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3-WATT SPEAKERS - Speakers are integrated to give you the option of listening to your shows, movies, music and programs without headphones.
AUDIO IN / OUT - Plug your media player into the console using the included adapter cable to play audio through the integrated speakers, or plug your headphones into the console to listen to through your own device.
ENERGY SAVER MODE - After 15 minutes of inactivity, the console switches to sleep status, which draws less energy.
WARRANTY
Frame: 7 Years Parts: 2 Year Labour: 2 Year
Complimentary curbside delivery Australia
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2011
Far From the Epitome of Healing
We humans are stuck with bodies that are far from the ideal of regenerative prowess: we are very frail in comparison to a great many other species. We don't regrow limbs or organs to any meaningful degree, we scar, lose functions, and die to a range of injuries that are easy enough to fall into. Break that poorly protected sack of innards and you won't be around for long enough to greatly regret it. So all told, evolutionary success is something of a low bar when it comes to resilience to wear, tear, and aging - and as a recent popular science article reminds us.
"The trouble is that humans and other mammals do not have a very good means of responding to loss of heart muscle. They cannot repair the heart as other creatures, such as zebrafish, can. There is no intrinsic mechanism to get cells to migrate into the heart to replace those that have been killed off by a heart attack."
Fortunately, we will soon be able to work around or remove human limitations of this nature through the application of biotechnology. Evolutionary pressure has done little for our robustness, but technology can do much more in the decades to come:
Unlike the approach taken by the team led by Paul Riley, which is concentrating on trying to simulate a patient's own stem cell population, Emanueli is working on techniques to deliver stem cells derived from other sources. The ultimate aim is to find a way to create sets of cells that can be put inside heart attack patients in order to stimulate the growth of new blood vessels. These cells are known as vascular endothelial cells and vascular smooth muscle cells and both play a crucial role in the construction of blood vessels that are destroyed in the heart in the wake of a myocardial infarction.
...
By contrast, Dr Anastasis Stephanou, at University College Hospital, London, is using a grant from the BHF to work - with his colleague Suwan Jayasinghe - on a technique aimed at "patching-up" a damaged heart. Their work exploits a form of spray technology that allows them to impregnate sheets of protein with biological material including aerosol suspensions of cells. The protein acts like a skeleton in which the cells can settle.
...
Several research groups round the world have recently reported success in using stem cell technology first to isolate fibroblast cells found in the skin and then to transform these into cardiac cells using various chemical interventions. "We envisage a person going into a hospital and being diagnosed with a serious heart problem. Once a diagnosis is made, a section of his or her skin would be removed and its fibroblast cells would be isolated. These cells would then be treated with chemicals and transformed into cardiac cells which can be used to create one of our sheets. This in turn would be taken by a surgeon and inserted into the damaged part of the patient's heart in the expectation that cardiac cells will be taken up and the heart's function restored."
These are small steps, but there are many different similar lines of work for the heart, and again more groups working on regeneration of other organs. Ultimately, this will all lead in to ways to address the damage of aging at earlier stages than a heart attack - incrementally restoring and maintaining the heart such that it never comes to that point of catastrophic failure, and doing the same for other organs and biological systems in the body.
Programming Cells to Go Where They Are Needed
Another step on the way to regenerative medicine that can repair and rebuild specific tissues: "Stem cell therapies hold enormous potential to address some of the most tragic illnesses, diseases, and tissue defects world-wide. However, the inability to target cells to tissues of interest poses a significant barrier to effective cell therapy. To address this hurdle, [researchers] have developed a platform approach to chemically incorporate homing receptors onto the surface of cells. This simple approach has the potential to improve the efficacy of many types of cell therapies by increasing the concentrations of cells at target locations in the body. ... While conventional cell therapies that include local administration of cells can be useful, they are typically more invasive with limited potential for multiple doses. ... You can imagine, that when the targeted tissue is cardiac muscle, for example to treat heart attacks or heart failure, injecting the cells directly into the heart can be an invasive procedure and typically this approach can only be performed once. ... Using the platform the researchers created, the cells are prepared to travel directly to the area of interest after being injected through a common and much less invasive intravenous infusion method. ... the approach can be used to systemically target bone producing cells to the bone marrow to treat osteoporosis, cardiomyocytes to the heart to treat ischemic tissue, neural stem cells to the brain to treat Parkinson's disease, or endothelial progenitor cells to sites of peripheral vascular disease to promote formation of new blood vessels. The researchers concluded that, as the understanding of the mechanisms of cell trafficking grows, the ability to improve homing to specific tissues through engineered approaches should significantly enhance cell therapy."
Longevity Science Would Benefit From a Carl Sagan Figure
Here's a question for you: why does the triumvirate of astrophysics, astronomy, and cosmology get such good press and widespread public approval in comparison to, say, the fundamental life sciences? I have to think it has something to do with the succession of scientists who evolved into successful media figures, educators, and advocates for their field, such as Carl Sagan, the present day Neil deGrass Tyson, or Patrick Moore - and I'm probably dating myself here by knowing of the existence of the latter. If asked to name noted scientists who went on to become media figures, off the cuff, I think I'd be hard pressed to quickly come up with more than one or two who didn't come from an astrophysical or similar background (right now my brain is delivering Attenborough, Dawkins, and blank). So clearly there's been a lot of groundwork accomplished over the past decades: bringing the broad field of physics and cosmology to the masses, and along the way gaining public support for the ongoing and often thankless work of understanding the universe and its myriad components.
A cynic might think that that having a massive government agency like NASA floating around for a good number of decades and spending lavishly on flashy programs intended in part to assure its own popularity might have something to do with it. I'd be that cynic, but it seems to me that most of the comparatively less popular and less beloved fields of scientific research are also ridden by large government agencies in the US - big budgets and just as much need for popular support. So I do think that there's something interesting going on here in that small sliver of the media spectrum that scientists have colonized. Something we can learn from.
To be a media figure of this sort is a career path option that's certainly open to researchers who garner either sufficient fame or media experience across the years, but for best effect it requires you to remove yourself from the business of science. The scientific community tends to behave like an aggravated immune system when confronted with someone who is both a media figure and actively publishing scientific research. Throughout history a great many people have subverted the scientific method for personal gain, using influence, fame, money, and other forms of corruption - and the modern media is all that rolled up into one neat package. Taking your work to the press before taking it to your peers is thus a grand heresy in modern science, one which leads to harsh judgement and excommunication. Consider what happened to the reputations of Pons and Fleischmann, for example. From that, all things associated with the mass media come to be eyed with suspicion by the rank and file scientists: publicizing a field is very welcome, but even the slightest hint of use of position to influence matters of publication is going to stir up wrathful mutterings at the very least.
So the scientist turned media figure must feel strongly enough about his field to want to be an advocate and educator, but must also essentially give up his work in favor of talking about what he used to do. Not, I think, the easiest of paths for someone who truly enjoys the scientific life.
Regardless, the future of longevity science - or the foundations of rejuvenation biotechnology, or SENS-like research, or whatever you want to call it - must come to include scientist-educators in the media. A Carl Sagan for this presently minor field must eventually arise: to my mind that will be one of the signs of growth and progress, meaning that it will happen as a matter of course along with (a) the expansion of the community of researchers actively working on ways to repair the damage of aging, and (b) increasing public awareness. But sooner is always better than later.
28
Oct
2011
The Culture and Practice of Science is Changing
The opening up of information, communication, and organization brought by the internet is changing business as normal in every field, making it far easier for ideas on the edge to gain support and activity. This is important for the development of rejuvenation biotechnology, as the changing nature of scientific work can speed the move to the mainstream, and allow for far more useful progress to be achieved while the flow of funding is still comparatively small: "our entire model of education and what it means to be a 'trained professional' is shifting. There's a hell of a lot of resistance from the status quo - which makes it difficult and inconvenient for rapid progress - but it isn't enough to stop it from happening. ... When the university system and the current PhD paradigm was invented, it was a different time. ... If you wanted to study advanced topics, or apprentice under someone famous to learn from their expertise, you needed to go to a university. But things are different now. Technology allows us access to some of the leading minds of our age [making] proximity to a university campus nearly irrelevant in order to meet other students and benefit from valuable peer-to-peer discussions. With the world's information available on the web, and with all of these advances in technology allowing for rapid data sharing and collaboration, how much value is there in the Ivory Tower? We are becoming a society of autodidacts, with information at our fingertips 24/7. Citizen Science is a natural consequence of that. Have an interesting scientific inquiry? Get on the web and investigate it. Learn from the millions of sources out there. Crowdsource some ideas, generate some hypotheses. Have discussions with others. Make a plan. Get your equipment. The scientific method is in-progress. Science is free for all to explore. Why waste time jumping through bureaucratic hoops when you can begin investigating what you want, when you want? Need to fund your research? Crowdsourced methods of funding, such as Kickstarter, are becoming more popular for these types of endeavors. Instead of 100 scientists chasing the same grant, why not go to the public and let them fund what they think is valuable? I think we'll be seeing a lot more of this in the future."
A Review of 100+ at h+ Magazine
Another review of Sonia Arrison's 100+: "I have to congratulate Sonia Arrison on putting together a book that is both highly accessible to newbies with no prior background in transhumanist thinking or longevity research, and also richly interesting to those of us who have playing in these regions of conceptual space for a long time. The main concepts in the book are indeed things I've been familiar with for a long time: (a) There is a host of rapidly accelerating technologies with the apparent capability of dramatically extending human healthspan, (b) Most likely, human psychology and society will adapt to dramatically increased human healthspan as it occurs, so that it will be experienced primarily as a Good Thing rather than as something traumatic or troublesome However, the book is packed with a sufficient number of interesting informational tidbits, that I found it well worth reading in spite of my general familiarity with the biology, psychology and sociology of radical longevity. ... Arrison reviews the key technological streams leading us toward radically increased healthspan - including gene therapy, stem cell therapy, Aubrey de Grey's SENS concept, artificial organs, tissue regeneration, the potential application of advanced AI to longevity research, and so forth. Both current research and envisioned future advances are considered. Then, in what is probably the greatest strength of the book, she considers the potential psychological and social impact of progressively increasing healthspan: the effects, as the book's subtitle indicates, on personal life, family relationships, marriage, careers and the economy etc. Combining common sense with appropriate invocations of rigorous research and statistics, Arrison provides the most systematic refutations I've seen of the standard anti-longevity arguments - 'death gives life meaning', 'overpopulation will starve or bankrupt us all', and so forth. Step by step, and in an invariably good-natured and friendly way, she demolishes these arguments, making a solid case that increased healthspan is likely improve rather than degrade our emotional health and family lives and enhance our careers and economies."
An Introduction to Cancer Stem Cells
The cancer stem cell hypothesis suggests that a majority of cancers are driven and supported by a small population of errant stem cells, and that these cells are characteristic in ways allowing them to be identified and destroyed. Without the cancer stem cells, a cancer would whither. In other words, cancer stem cells offer the hope that there are in fact broad commonalities in the mechanisms of different forms of cancer, and that this fact will lead to a unified, single technology platform and robust cures for even late-stage cancers.
The existence and universality of cancer stem cells is a hotly debated topic in medical research, and rightly so for the reasons given above. Good evidence and arguments can be found on either side. Is cancer something that can be solved through a single mechanism or group of very similar mechanisms? Or only some cancers? Or only few cancers? These are important questions, and the answers, when they arrive, will tell us whether the prospects are for many cures arriving soon or for a slow and incremental flow of therapies over decades.
Today I noticed a good introductory popular science article that walks through the present state of research and scientific thought on this topic, and provides copious references along the way. You might find it interesting:
Take some cells from a tough-to-treat tumor, sort them, and inject each fraction into a different immunodeficient mouse, and only a small percentage of those cells will thrive and form tumors. This sort of experiment illustrates a concept that has been gaining traction within the cancer research community. Tumors contain a diverse mixture of cells, and only a handful of them can bounce back after treatment. That deadly minority can reproduce indefinitely and differentiate into a wide variety of cell types, just like stem cells. And often they express many of the same genes that are active in induced or embryonic stem cells and inactive in mature tissue.
...
The logic of pursuing therapies that might zero in on cancer stem cells is compelling to many. But the methods to evaluate such therapies' effectiveness, or to personalize cancer treatments according to stem cell markers, are not nearly as well developed. Without an array of proper markers, it's hard to tell whether drugs that target cancer stem cells are working as intended. ... Things are looking up for genetic analysis, but the poor reliability of cancer stem-cell-surface markers remains a confounding problem. For nearly a decade, biologists have known that antigens such as CD133 can be found on the surfaces of cancer stem cells. But these markers are not particularly specific.
...
But for solid tumors, which account for about 85% of all cancer diagnoses, the search for such stem-cell-surface markers is still in the early days. In such [cancers] cell-surface markers can vary from one type of cancer to another or even from one cell within a tumor to another. Until better markers are discovered [the] cancer stem cell field will remain somewhat embryonic.
27
Oct
2011
More Work on Epigenetic Age Determination
A number of different research teams have recently demonstrated epigenetic markers that can be used to establish chronological age or predict life expectancy to various degrees. Here is another: "Aging has been associated with accumulation of cellular defects such as DNA damage and telomere shortening. On the other hand, there is accumulating evidence that aging rather resembles a developmentally regulated process which is tightly controlled by specific epigenetic modifications. ... All tissues of the organism are affected by aging. This process is associated with epigenetic modifications such as methylation changes at specific cytosine residues in the DNA (CpG sites). Here, we have identified an Epigenetic-Aging-Signature which is applicable for many tissues to predict donor age. ... This Epigenetic-Aging-Signature was tested on a validation group of eight independent datasets corresponding to several cell types from different tissues. ... The average absolute difference between predicted and real chronological age was about 11 years. ... It has to be noted, that chronological age is not identical with biological age and it is conceivable that some of the discrepancy between predicted and real age can be attributed to this difference - further research might facilitate determination of the biological age for personalized medicine."
Speculating on the Timeline for Artificial Blood
There are a number of different lines of research focused on developing artificial blood or culturing blood to order from stem cells: "Clinical trials using blood created from adult stem cells are set to begin within the next two or three years, raising the prospect it could soon become routinely used where real blood is unavailable. Scientists are also developing alternative bloodlike substances which could be injected into the body as a 'stopgap' until an actual blood transfusion could be performed. ... modern doctors have minimised the risk of patients receiving infections such as Hepatitis A and C during transmission [but] blood produced from stem cells would avoid these risks and could be manufactured as type 'O-negative', which is produced by just 7 per cent of the population but is suitable for use in into up to 98 per cent of patients. ... It could also be used in certain hospital situations, for example in elective surgery, and save hundreds of thousands of lives in parts of the world where blood banks are not available. [Researchers have] developed a method of taking adult stem cells from bone marrow and growing them in the laboratory to produce cells which look and act almost identically to red blood cells. Once their technique is fine-tuned the team may consider using stem cells taken from embryos, or reprogrammed skin cells, instead of adult cells because although the end product does not mimic red blood as closely, they can be grown in much greater quantities in the lab. ... A more radical solution, which [researchers] say could be perfected within five to 10 years, is to develop a completely artificial alternative to blood which performs the same key functions and would be safe to use in patients of every blood type. This could involve packing haemoglobin - which carries oxygen around the body - into a synthetic cell-like structure, or using a chemical to hold the haemoglobin together so that it can be injected without the need for red blood cells."
Join us for a fascinating discussion with Dr. Aubrey de Grey, Chief Science officer of the SENS Foundation (SENS stands for "Strategies for Engineered Negligible Senscence"), on the topic of "Regenerative Medicine Against Aging."
Dr. de Grey has been a provocative and polarizing figure in the scientific and medical communities' dialogue on the topic of life extension, and the approaches that will
lead to dramatic increases in quantity and quality of life.
According to Dr. de Grey, "the first human who will live up to 1,000 years is probably already alive now, and might even be today between 50 and 60 years old."
You might look back into the archives for an explanation of the 1,000 year life span: this is an estimated life expectancy for someone who does not age to death, thanks to a rolling series of advances in rejuvenation medicine that eventually add more than a year of additional life with each passing year of research and development. If you examine mortality rates due to other causes projected out over time, you see that an effectively ageless person will live for at least a millennium under the mortality rates of today, not considering any future reductions in the rate of death by accident thanks to advances across the board in technology.
26
Oct
2011
Keeping an Eye on Amyloid Vaccine Development
The SENS Foundation has published a series of posts over the past year or so that follow progress in the development of immunotherapies to remove the age-related buildup of amyloid in the brain - much of it intended as treatments for Alzheimer's disease. Success here will, however, lead to a broader technology platform that might ultimately be turned against any damaging aggregate that builds up in the body with age. These aggregates contribute to aging itself, and so removing them is one necessary part of any comprehensive rejuvenation biotechnology package: "soluble and insoluble aggregates of beta-amyloid protein (Aß) and other malformed proteins accumulate in brain aging and neurodegenerative disease, leading progressively to neuronal dysfunction and/or loss. These have long been widely accepted to be drivers of Alzheimer's disease (AD) and other age-related dementias and neurological disorders such as Parkinson's disease, and it has recently become increasingly clear that neuronal protein aggregates are the main driver of 'normal' cognitive aging. To prevent and reverse the course of neurodegenerative disease and age-related cognitive dysfunction, the regenerative engineering solution is therapeutic clearance of extracellular aggregates (such as Aß plaques) and intracellular aggregates (such as soluble, oligomeric Aß). Immunotherapeutic Aß clearance from the brain is a very active field of Alzheimer's research, with at least seven passive, and several second-generation active, Aß vaccines currently in human clinical trials. ... . We now have a published report of preliminary findings from the first Phase I trial in an Aß-targeting vaccine with novel properties, and with the benefit of preliminary findings of outcomes that have only emerged with the experience of its forerunners in previous clinical trials."
Correlating Immune System State With Health in Old Age
Via ScienceDaily: "Exceptional cognitive and physical function in old age leaves a tell-tale immunologic fingerprint, say researchers ... Likewise, older adults who have mild impairments bear a distinct immunologic pattern, too. ... Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed. The immune system is dynamic, and the changes it undergoes over time very much influence function. ... For the project, the team collected blood samples from 140 participants who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades and were 78 to 94 years old. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants' health and function, medical history and hospitalizations, and self-rated health, and assessed their cognitive and physical function using standard tests. Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells ... A closer look in the new study shows that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independently of the conventional ones. The functionally resilient elders also have a distinct profile of blood proteins called cytokines that reflect an immune-enhancing environment. ... Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and they have a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness."
The trouble with surgery is that it is risky: major, involved surgeries bear a non-trivial risk of death even in the most advanced clinical surroundings, and that risk grows with age. Old people suffer a general frailty due to the damage of aging that makes it progressively less likely for them to survive any given surgical procedure. When you consider that every major organ is going to have issues if we live long enough without access to general biological repair technologies that remove the cellular and molecular damage that lies at the root of tissue dysfunction in aging, that's a bunch of major surgeries to look forward to.
So I believe we should look on the forthcoming phase of tissue engineering as a transitional period: organs will be built from scratch and transplanted until such time as the state of the art allows our existing organs to be incrementally repaired and rebuilt in situ instead. Eliminating the need for surgery is a big deal, and so in the long term I think that the future belongs to the branch of regenerative medicine that delivers populations of tailored stem cells into damaged tissue. As the research community becomes every better at precisely controlling the behavior and activities of cells, even that step of delivering new cells into the body may go away, to be replaced with adaptive drug-like therapies that issue commands to the body's existing cells through signaling pathways or induced epigenetic alterations, and which react to guide the ongoing state of repair.
Either way, surgery is not a desirable outcome - it's a least worst path at the best of times. In the future of medicine and aging, everything that can be achieved without surgery should be achieved without surgery, and we'll all be better off for it.
25
Oct
2011
A Role for Sirtuins as Cancer Suppressors
Work on sirtuins as longevity genes hasn't exactly shown promise, but there are still interesting things to be learned from the work taking place, as this open access paper shows: "One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor."
Retrotransposons and Genetic Instability in Aging
The degree to which progressive mutation of nuclear DNA causes aging is debated, but here is some work on the mechanisms: "Genetic damage through mutations and genome rearrangements has been hypothesized to contribute to aging. The specific mechanisms responsible for age-induced increases in mutation and chromosome rearrangement frequencies and a potential causative role for DNA damage in aging are under active investigation. Retrotransposons are mobile genetic elements that cause insertion mutations and contribute to genome rearrangements through nonallelic recombination events in humans and other organisms. We have investigated the role of endogenous Ty1 retrotransposons in aging-associated increases in genome instability using the Saccharomyces cerevisiae chronological aging model. We show that age-induced increases in loss of heterozygosity and chromosome loss events are consistently diminished by mutations or treatments that reduce Ty1 retrotransposition. Ty1 mobility is elevated in very old yeast populations, and new retromobility events are often associated with chromosome rearrangements. These results reveal a correlation between retrotransposition and genome instability during yeast aging. Retrotransposition may contribute to genetic damage during aging in diverse organisms and provides a useful tool for studying whether genetic damage is a causative factor for aging."
We believe that it is possible and necessary to eliminate aging and even death, and to overcome the fundamental limits of the physical and mental capabilities currently set by the restrictions of the physical body. ... We believe that this country still possesses the necessary scientific and technical potential that will allow us to embody such a lofty objective. Such a project will turn Russia into the world's ideological leader and will revive the leadership status of our country in many different scientific and technical areas.
Willingness to get up and try is the first necessary step on any path, and a great deal of the work at present in advocacy for rejuvenation biotechnology lies in drumming up the will to try to extend human life at all. All too few people think about it or even much care, sad to say. If Russian scientific pride - something that I think isn't all that unreasonable, given the achievements made by that community under the circumstances forced on them by history - makes a difference, then I'm all for it.
To my eyes, the most interesting aspect of this Russia 2045 initiative is that, unlike any other serious proposal I'm aware of, their focus is on getting out of biology and into machine bodies as rapidly as possible. Bear in mind that in the long term every plan for radical life extension ends up with we humans changing out our biological parts for machinery - but that is generally proposed to happen somewhere past the point at which nanotechnology supersedes biology in terms of effectiveness, when there is increasingly little difference between biological and nanoscale machine systems. Both operate on the scale of single molecules, but the artificial system will be much better at it than the natural system - because it will be designed rather than evolved. We will replace our biology with machinery because the machinery will ultimately get the job done much more effectively.
Until that time arrives, however, much of the longevity science movement focuses on biotechnology, medicine, and the development of other ways to keep the biology we have repaired and in good shape. Not so for Russia 2045, however. The early parts of their plan look much like this:
Develop an electromechanical body-shaped chassis.
Develop a robust, lightweight life support system for the brain.
Decant the brain into the life support system, and place the system in the body-chassis.
Lastly, incrementally improve the body-chassis to better serve its role as a mind carrier.
In essence, this is a course to throw away as much of the body as possible as soon as possible - a path based on a different set of preconceptions about difficulty and efficiency on the road leading to an artificial brain hosting a once-biological human mind. If aiming for life spans of thousands of years, this is the exactly same place we'll get to in the end even if we start out by maintaining our biological bodies and brains for as long as possible through rejuvenation biotechnologies. I'll point you to an article entitled The Million Year Life Span or back into the archives for a piece on whole brain emulation if you're interested in thinking about the stage of replacing the biological brain with a machine brain - I won't talk about that today. It's certainly a long way off in comparison to a range of more important first steps on the road to greatly extending healthy human life.
Instead, let's consider how the next twenty years of "robot body as fast as possible" might unfold, and what advantages and disadvantages that might incur in comparison to a strategy that focused instead on rejuvenation biotechnology and keeping our fleshy bodies. I would hope that we can all agree that efficient humanoid artificial bodies will be realized in this time frame: between the robotics and the powered exoskeleton industry (both for military use and as a replacement for wheelchairs for the disabled), a lot of people are already working on this. The real challenges here are:
A reasonably complete, safe, and reliable neural-computer interface
A robust and safe life support system for a disembodied brain
I don't think that either of these can be seen as much off the starting blocks at this point - it's still the case that every small advance in working with neural interfaces is widely touted, and in the grand scheme of things those advances are not all that impressive. Researchers remain a long way away from being able to provide good images to the brain, or correctly identifying general intent and language use from brain activity. Without progress in a general neural interface to allow communication and action, I can't see much impetus in the scientific community for building a brain life support system - the ethics groups would shut that down pretty quickly.
Thus my wild stab in the dark guesstimate is that the research community is at this time better placed to realize SENS than it is to build a full neural interface. Other folk may know better than I on that front. Either way, this isn't a critique of plausibility regarding the technology; building these systems is a very plausible long-term goal. There's no strong objection from physics or physiology, but both are very hard tasks. In taking this path, research and development groups would be substituting the difficulties of much of rejuvenation biotechnology with the difficulties of electromechanical systems and brain-machine interfaces.
The first objection that came to mind after looking over the Russia 2045 vision is much the same as my objection to WILT: in ideal circumstances, it will lead to extended life, but only for so long as you have access to a technology base capable of maintaining your (bio)technologies. If you fall off the wagon and out into the wilderness for a few decades, then you will probably die, or at least suffer a greatly raised risk of death and serious systems failure. There are certain advantages to an approach to longevity based as much as possible on repairing the biology we have: we know that what we have is fairly robust.
In any case I encourage you to look over the Russia 2045 website. Progress towards any given goal depends on a healthy competition between different practical methodologies, and the "straight to the machine body" school of thought hasn't gathered as much support as it might in recent years, and nor has a body of work accumulated to explain exactly how the next twenty to thirty years would run under this scenario. I look forward to seeing that change.
24
Oct
2011
On the Mitochondrial Theory of Aging
A layperson's explanation of the theorized role of mitochondria in driving aging can be found at h+ Magazine: "Aging is a complex process that, by nearly all educated accounts, appears to involve multiple different interacting processes. Aubrey de Grey has sought to break down the causes of aging into seven categories; others have presented different understandings. One perspective on aging broadly recognized as important, however, is the mitochondrial theory - tying aging to changes in the function of mitochondria, the energy powerhouses of the cell. This article reviews the mitochondrial theory of aging, with an aim of describing enough of the science to give the lay reader a real sense of what the theory is about. ... In the mid-1950s, Denham Harman proposed that aging results from accumulated damage inflicted by free radicals - atoms or molecules possessed of a sole unpaired electron in their outer shells. ... In 1972 Harman proposed the Mitochondrial Theory of Aging (MTA), which is considered an extension of the free radical hypothesis. According to this theory, aging is due to the cumulative effects of damage wrought by free radicals on the mitochondrial DNA and function. ... Taken together, data derived from several thousand studies largely supports the MTA. Mitochondrial fee radicals damage the mitochondrial DNA, causing mitochondrial dysfunction with lowered ATP production, cellular energy depletion and death, resulting in aging."
A Report From the Singularity Summit
From Singularity Hub: "scientists, engineers, futurists, and other forward-thinkers converged for Singularity Summit 2011. ... In this first part of three [we'll] highlight the speakers who discussed the various aspects of health related to the singularity. This includes life extension and regenerative medicine as well as the implications of these new technologies. ... Hands down, one of the most exciting talks of the first day. Dr. Stephen Badylak was able to wow the crowd with his work on regenerative medicine ... Working at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, Badylak and his team have been experimenting with what's known as the extracellular matrix (ECM), the structural component in animal tissue outside of the cells. Research has found that besides providing support for cells, the ECM acts as a 'information superhighway', allowing cells to communicate with each other. Part of this communication involves molecular signals that recruit stem cells after injury and indeed, grafting pig ECM at sites of human injury have been shown to work better at regenerating tissue than injecting stem cells directly. ... Dmitry Itskov presented on a new movement that he has founded to tackle the issue of human immortality. Itskov gave a somewhat nationalistic presentation, touching on many aspects of why Russia is poised to become the leader in the area of longevity. He described the work of famous Russian scientists that are the intellectual grandfathers of this movement and gave an open invitation to anyone who wanted to help grow it. As was a common theme throughout the 2-day summit, Itskov doesn't think that the breakthroughs in the technology to bring radical life extension to market will necessarily come from government. Instead, he advocates grass-roots movements [that] assemble the necessary scientists, thinkers, and financiers to see it through."
A Speculative Timeline for Xenotransplantation Trials
Xenotransplanation is the use of animal organs, possibly genetically modified, in place of human organs for transplantation in cases of organ failure or damage. This is one of the developing technologies that will compete with electromechanical or bioartificial organs and tissue engineering of whole organs to make organ replacement a far more viable, effective, and low-cost prospect than it is today. To my eyes xenotransplantation was always going to be a transitional technology, economically viable for a period of years in which tissue engineering was still finding its feet, but the development of decellularization has made animal organs look like a far more interesting long term source of raw materials.
a valve from a human or animal donor is removed of all cells using tissue engineering, so that only its outer framework remains. This valve matrix is then colonised with cells that have been obtained from the blood of the recipient and propagated. Within a few weeks, a quasi-natural heart valve then emerges in this bioreactor, that exhibits no rejection response or other faults, but instead grows with the patient after the implantation. ... Recellularization makes xenotransplantation a much more viable technology to fill the tissue engineering gap prior to the ability to grow complex organs from scratch.
The use of the patient's own cells in a donor scaffold removes issues of immune rejection, wherein the patient's immune system attacks and destroys the donor organ. When immune rejection is removed from the equation, not only does the entire process become much safer and cheaper, we are left with the extracellular matrix organ scaffold as the actual raw material required. A full organ scaffold is presently too complex for researchers to construct from scratch, and even when this can be done at some point in the next decade or two, it will be expensive for a time thereafter. Obtaining the decellularized scaffolds from human organs puts you right back to where you started with the difficulties of sourcing donor human organs when needed, but using animal organs can work around that issue.
I noticed a recent article that discusses the timelines for present work on xenotransplanation without decellularization, which is largely focused on transferring cells and small sections of tissue rather than whole organ structures. Organs are clearly on the agenda, however:
During the past decade xenotransplantation, the use of animal organs, tissues or cells in humans, has made great advances. Due to the fact that more and more genetically modified pigs are available with genes to protect them from human immune response, has alleviated earlier problems in helping humans to accept such transplants. ... at this time the longest time of survival for pig organs in non-human primates varies from a few days in lung transplants to approximately 6-8 months in hearts transplants. Although research is still years away from conducting human trials of solid organ transplants of this nature, lifesaving transplants of a pig heart or liver could pose as an alternative solution until a human organ becomes available. At present researchers are investigating strategies to incorporate human anticoagulant or antithrombotic genes into genetically modified pigs, and additional genes to regulate the human inflammatory response.
...
The authors also discussed in terms of organs, that stages of other strategies are currently more advanced than xenotransplantation, such as left ventricular assist devices for cardiac support. However, they agree that given time, transplanting a pig's heart will prove to be the better option compared to using a mechanical device.
...
Although remaining issues are delaying clinical implementation, experimental results obtained with pig islet, neuronal-cell, and corneal xenotransplantation have been encouraging. With new genetically modified pigs becoming available that are likely to improve the outcome of cellular and corneal xenotransplantation further, we believe that clinical trials will be justified within the next 2-3 years. No safety concerns that would prohibit such clinical trials have been reported...With regard to pig tissues and cells, as opposed to organs, it would seem that clinical xenotransplantation could soon become a reality.
21
Oct
2011
Working on Building Blood Vessels with BioRap
Another group working on machinery to produce tissue engineered blood vessels: "German researchers have been working at growing tissue and organs in the laboratory for a long time. These days, tissue engineering enables us to build artificial tissue, although science has still not been successful with larger organs. Now researchers at the Fraunhofer group of applied research institutes are applying new techniques and materials to come up with artificial blood vessels in their BioRap project that will be able to supply artificial tissue and, perhaps, even complex organs in the future. ... The aim of tissue engineering is to create organs in the laboratory for opening up new opportunities in the field. Unfortunately, researchers have still not been able to supply artificial tissue with nutrients because they do not have the necessary vascular system. Five Fraunhofer institutes joined forces in 2009 to come up with biocompatible artificial blood vessels. It seemed impossible to build structures such as capillary vessels that are so small and complex and it was especially the branches and spaces that made life difficult for the researchers. But production engineering came to the rescue because rapid prototyping makes it possible to build workpieces in line with any complex three-dimensional (3D) model. Now scientists at Fraunhofer are working on transferring this technology to the generation of tiny biomaterial structures by combining two different techniques: 3D printing technology established in rapid protoyping and multiphoton polymerisation developed in polymer science."
The Logical Next Stage of Targeted Cancer Therapies
A look at what comes after merely targeting cancer cells: "Several decades from now we hope to have sophisticated medical nanorobots, produced by molecular manufacturing, that can enter cells, analyze the state of the cell, and initiate appropriate therapy, such as killing cancer cells. A team of scientists [has] taken an important step in that direction by demonstrating a synthetic circuit that, when incorporated into a cell, detects the presence or absence of five specific small RNA molecules,processes that information, and then, based upon that result, either kills or does not kill the cell. ... [The] long-term goal is to construct biocomputers that detect molecules carrying important information about cell wellbeing and process this information to direct appropriate therapeutic response if the cell is found to be abnormal. ... The researchers constructed what they describe as a 'classifier' gene circuit that is transiently expressed inside a cell and then integrates information from five molecular markers to determine the state of the cell, and then produces a protein that sets off the cellular suicide cascade if the cell is determined to be cancerous. The DNA circuit they constructed contains numerous control sequences chosen from standard genetic engineering toolkits that respond to specific miRNAs such that only the combination that identifies the particular cancer cell line used in the experiments activates the circuit and triggers the onset of cellular suicide. The results presented do show some false positives and some false negatives, so further optimization of the genetic circuit would be needed. Nevertheless, the results are impressive. Also, in principle, this method could be adapted to different cell types by choosing the combination of miRNAs appropriate to distinguish that cancerous cell from neighboring cells."
Proactively Adjusting Your Own Mortality Risk
Much as none of us like to think about it, we all have an ongoing, changing mortality risk - the flip side of the statistics of life expectancy at any given age. This largely involves cars in younger years, but then goes on to be dominated by the unpleasant and varied consequences of aging to death. I have no sage advice when it comes to cars, but I can point out the science that backs up the idea that we have a modest degree of control over our risk of death at any given age, and hence over our life expectancy.
I don't expect to see significant additions to this list become widely available for another twenty years or so. Aside from the fact that we can do a great deal to speed up the advent of ways to repair the cellular and molecular damage of aging - which is a very big deal - the healthy person interested in putting a thumb on the scales of mortality risk is presently stuck with much the same narrow array of methods as our immediate ancestors. There's an anti-aging marketplace shouting loudly that they have plenty of new things to try, but their marketing folk are largely lying through their teeth, hyping things with no scientific basis, or selling goods that have statistically negligible effects in comparison to exercise and calorie restriction.
But so it goes - there are always people who want answers now, and never mind whether they are the right answers, and so there will always be other people selling immediate answers. Fools and their money, and so forth...
For Meeting the WHO´sA new study concludes that men who experience persistently moderate or high levels of stressful life events over a number of years have a 50 percent higher mortality rate. ... This is the first study to show a direct link between stress trajectories and mortality in an aging population. Unlike previous studies that were conducted in a relatively short term with smaller sample sizes, this study was modified to document major stressors - such as death of a spouse or a putting a parent into a retirement home - that specifically affect middle-aged and older people.
A Review of the State of Tissue Engineering of Cartilage
An open access review paper: "In tissue engineering fields, recent interest has been focused on stem cell therapy to replace or repair damaged or worn-out tissues due to congenital abnormalities, disease, or injury. In particular, the repair of articular cartilage degeneration by stem cell-based tissue engineering could be of enormous therapeutic and economic benefit for an aging population. ... Many people over the age of 40 suffer from degeneration or injury of their cartilage, leading to a reduced workforce and increased medical expenses. Thus, improvements in cartilage repair using a cell-based tissue engineering approach will greatly benefit public health and the economy. Personalised cell therapy for cartilage repair using cell-based tissue engineering technologies would provide clinically practical methods for producing a cartilage tissue equivalent. A number of biomaterials are available as scaffolds, and research continues to help us understand more details about how tissues develop and which cell type should be applied. These studies have provided details of how tissues grow in vitro and in vivo, but clinical applications depend on working with surgeons and the translation of these materials and technologies to in vivo models that are more relevant to patients. When cell-based cartilage tissue engineering technologies are applied to new animal models, we attempted to find better functional compositions for successful applications than were observed in previous studies. Although stem cell-based cartilage tissue engineering systems may demonstrate success even in animal models, there are a number of new challenges when the technologies are applied to humans. Further research on in vivo application must address immunological issues, integration of host and stem cell-based engineered cartilage, and the variability of tissue development in an in vivo environment, depending on surrounding disease processes, age, or physical activity. Therefore, interdisciplinary studies are not only necessary but crucial before cell-based cartilage tissue engineering can reach its full potential in cartilage repair and regeneration."
Another Look at Epigenetic Inheritance of Longevity
Researchers investigating calorie restriction have noticed that its effects on longevity can be inherited through epigenetic variations - which makes sense, given the reasons why individual longevity variations in response to available food evolved in the first place. If it is advantageous for a given individual at a given time to shift metabolism into a mode that allows it to live longer due to a decline in available food, then it's probably also advantageous for the children to do that from birth as well: "The tiny soil-dwelling worms C. elegans, when given mutations that make them live longer, transmit that trait even when their progeny don't inherit the life-extending mutations. ... Although much more research remains to be done, the new study raises the tantalizing possibility that if Grandma practiced caloric restriction - which affects the expression of longevity-enhancing genes - her descendants might reap the benefits. The inheritance occurs through "epigenetics": alterations not in the coding sequence of DNA (those ubiquitous A's, T's, C's, and G's) but in chemical changes that affect whether genes are expressed. ... [A] protein complex called ASH-2 [alters] histones in C. elegans, reconfiguring the histone-DNA complex into an 'open' state that promotes gene expression. Deficiencies in ASH-2 extend the worm's life span by as much as 30 percent. ... [researchers] blocked the three key proteins that make up the ASH-2 complex by mutating their genes. As expected, the worms lived longer - typically, an extra seven days beyond their lab life span of 20. [Researchers] bred the mutated worms with normal worms until their descendants no longer had the mutations. Nevertheless, the progeny still lived longer, as did their own descendants: even though their genes for the key proteins were normal, an epigenetic memory of longevity persisted."
Exercise, Longevity, and Long Term Medical Costs
One longevity-related line item that doesn't come up often enough in discussion is the matter of the expected state of your wallet as you move through life. Given that you have a fair degree of control over your long-term health, do you also have the same degree of control over the funds needed for future medical treatment? Reliability theory, a consideration of aging as damage, suggests that the only paths to a longer life are those which reduce or repair the accumulated biological damage that leads to aging. Reliability theory also tells us that this will lead to a lower chance of systems failure - which we might interpret as a lower chance of the need for medical intervention at any given time.
Thus it makes sense to look at the foreseeable biotechnologies of enhanced longevity as a way to reduce long term expenditures on medicine, on average, for individuals. One might hope that everyone - and not just those who have nursed an aging car through its last years - understands the difference in maintenance costs for a well-repaired machine versus one that's showing all the signs of accumulated wear and tear. Damaged machines spiral down into ever more expensive breakdowns, and that's just as true of people as it is of the things people build. Yet much of the public debate over medicine seems to focus on the idea that living longer implies greater medical expenditure - possibly another aspect of the Tithonus Error, the naive belief that living longer though biotechnology means being old for longer rather than being young for longer.
(As an aside, unrelated to the present point, the prospects for greater expenditure in the field of medicine would be a sign for rejoicing in a sane world. It would mean an industry primed for growth, needing more workers, gathering funds for investment in new ways to serve the growing number of customers, and so forth. No-one complains when the demand for cars, shoes, or shiny internet sharing widgets increases. Yet because medicine is so completely socialized in countries like the US, you see the inevitable spiral towards rationing, rejection of expenditures, and decay of new development rather than a healthy, competitive industry).
The tools for personal longevity will, I think, remain crude for the next couple of decades. Essentially, exercise, calorie restriction, and the avoidance of sharp things. Amazing things are happening in the labs, and we can clearly see how to extend life - but amazing in the lab doesn't yet translate to available in the clinic, and won't for a while. But even with these crude tools, barring genetic bad luck (or any of the other fatal forms of bad luck), the vast majority of us have a fair degree of control over our future health and medical budget. You might look at this open access paper, for example:
The authors followed up 27,738 participants aged 40-79 years and prospectively collected data on their medical expenditure and survival covering a 13-year-period. Participants were classified into those walking <1 and ≥1 h per day.
...
The present results indicate that the multiadjusted lifetime medical expenditure from the age of 40 years for those who walked ≥1 h per day was significantly lower by 7.6% in men and non-significantly lower by 2.7% in women than for those who walked <1 h per day. This decrease in lifetime medical expenditure was observed in spite of a longer life expectancy (1.38 years for men and 1.16 years for women) among those who walked ≥1 h per day. Thus, a healthy lifestyle not only extended longevity but also decreased the amount of lifetime medical expenditure, especially men.
It would be interesting to see the results on medical expenditure in a similarly large study that focused on deliberate exercise as opposed to time spent walking - but I think this illustrates the point, even with the smaller differences in life expectancy and health than are typically seen in studies that compare sedentary people with those who exercise regularly.
19
Oct
2011
Studying Methionine Restriction
The response of metabolism to lowered methionine intake appears to be a major component of the mechanisms of calorie restriction: "Methionine dietary restriction (MetR), like dietary restriction (DR), increases rodent maximum longevity. However, the mechanism responsible for the retardation of aging with MetR is still not entirely known. As DR decreases oxidative damage and mitochondrial free radical production, it is plausible to hypothesize that a decrease in oxidative stress is the mechanism for longevity extension with MetR. In the present investigation male Wistar rats were subjected to isocaloric 40% MetR during 7 weeks. It was found that 40% MetR decreases heart mitochondrial ROS production at complex I during forward electron flow, lowers oxidative damage to mitochondrial DNA and proteins, and decreases the degree of methylation of genomic DNA. ... These results indicate that methionine can be the dietary factor responsible for the decrease in mitochondrial ROS generation and oxidative stress, and likely for part of the increase in longevity, that takes place during DR. They also highlight some of the mechanisms involved in the generation of these beneficial effects."
Bioengineering Skin
An example of present work in growing skin from stem cells: scientists "are participating in research to study how to make use of the potential for auto regeneration of stem cells from skin, in order to create, in the laboratory, a patient's entire cutaneous surface by means of a combination of biological engineering and tissue engineering techniques. Skin is a tissue that naturally renews itself throughout our lives thanks to the existence of epidermic stem cells. ... We have found that this regenerative potential can be preserved in vitro (in the laboratory) if the cells are joined and become part of generated skin using tissue bioengineering techniques. ... The researchers have already been able to join together these epidermic stem cells into skin created by means of bioengineering, and they have observed that the cells preserve the regenerative potential that they normally have in our skin. That is, using a small biopsy from a specific patient, they can generate almost the entire cutaneous surface of that individual in the lab. ... The regenerative capacity of epidermic stem cells in these conditions is overwhelming, and it leads to the possibility of using these cells as a target for even more complex protocols, such as gene therapy. ... In fact, these researchers have already demonstrated, at the pre-clinical level, that it is possible to isolate epidermic stem cells from patients with different genetic skin diseases, cultivate them and, using molecular engineering as a first step, incorporate the therapeutic genes into each patient's genome to take the place of the one that the patient does not have or that functions abnormally. Afterwards, in the second step, the stem cells would be assembled into patches ready to be transplanted onto the patients."
Abusing the Meaning of Coercion
There's an article over at Reason Magazine today that calls out one example in a pattern of abuse of meaning that I've long found threatening. Attempts to fundamentally rework the meaning of a basic and important word are one of those little fragments of 1984 that manage to drift into the real world, an unsavory activity in which the meaning of the word is both kept and entirely inverted at the same time. I think the following quote captures the essence of this particular case:
Lawler, a member of President George W. Bush's controversial Council on Bioethics, tried to make the case that using technology to radically extend human lifespans, and boost human intellectual, emotional, and physical capacities, will end in coercion. Those who don't want to take advantage of the kinds of enhancements that biotechnology, nanotechnology, and cognitive technology will offer, argues Lawler, will ultimately not have a choice about using them. ... But is that so? If anyone should be concerned about coercion, it is the transhumanists who rightly fear that bioconservatives like Lawler will try to use the power of the state to halt the research that would lead to the development of enhancements would enable them to improve their life chances and those of their children.
Shades of Freedom is Slavery march through all too many minds, methinks. That is a real threat, as halting and slowing research in the life sciences is something that the bureaucrats of the modern state are very good at indeed. That people carefully try to invert the word "coercion" to mean "the existence of freedom of choice that I personally do not approve of" is also a threat, as freedom of choice and freedom from coercion are the deep roots of wealth and technological progress. Without them, you end up living in something akin to the backward ruins and ruined, predatory culture of the final years of the Soviet Union.
Freedom of research is, in essence, economic freedom, which is no different from personal freedom - the freedom to invest and work in whatever arrangements you can freely agree upon with other people. The most rapid progress occurs in free marketplaces, free for the exchange of ideas, free for association with others for mutual benefit, free for the exchange of goods. Any and all interference by centralized entities - such as governments - is inefficient and serves only to slow things down, make goods more expensive, and ensure that some research never happens at all.
Further, freedom is the very essence of transhumanism itself, which is no more than the human imperative to create new choices where before there was nothing. Having a choice today in an area where there was no choice yesterday is an increase in your freedom, and building those new choices - these new freedoms - is exactly what humanity achieves through technology:
Transhumanism, make no mistake, is just a fancy name for common sense. Change for the better is good, right? Common sense. It's what we humans do in our scattered finer moments - we work to change things for the better. It's common sense to fetch in the harvest on wheels rather than on foot, and it's common sense to repair the biomolecular damage of Alzheimer's before the mind begins to rot. It's common sense to build perfect immune systems from nanomedical robots, and it's common sense to develop the technologies of regenerative medicine to their logical end. It takes work, but what is work compared to a world of suffering? Choosing not to attain these goals makes about as much sense as standing out in the rain to spite yourself.
The Soviet Union may be gone in all but the longer memories, but there is no shortage of people who would strive to rebuild it again, today, in their country, one piece at a time. There are so many petty would-be totalitarians in this world, each laboring under the belief that central control of the matters they care about will work - this time! - if it is just done their way. The real danger of centralized government is that sooner or later, those would-be totalitarians get their hands on their ability to do real harm by attempting to enact their visions.
18
Oct
2011
Discussing the Near Future of Tissue Engineering
From MSNBC: "The latest science and schemes for achieving long life and the "singularity" moment of smarter-than-human intelligence came together at the Singularity Summit held [in New York] October 15-16. Some researchers explored cutting-edge, serious work about regenerating human body parts and defining the boundaries of consciousness in brain studies. ... The most immediate advances related to living longer and better may come from regenerative medicine. Pioneering physicians have already regrown the tips of people's fingers and replaced cancer-ridden parts of human bodies with healthy new cells. ... Success so far has come from using a special connective tissue - called the extracellular matrix (ECM) - to act as a biological scaffold for healthy cells to build upon. Badylak showed a video where his team of surgeons stripped out the cancerous lining of a patient's esophagus like pulling out a sock, and relined the esophagus with an ECM taken from pigs. The patient remains cancer-free several years after the experimental trial. The connective tissue of other animals doesn't provoke a negative response in human bodies, because it lacks the foreign animal cells that would typically provoke the immune system to attack. It has served the same role as a biological foundation for so long that it represents a 'medical device that's gone through hundreds of millions of years of R&D'. ... If work goes well, Badylak envisions someday treating stroke patients by regenerating pieces of the functioning human brain."
p38 MAP Kinase and Fly Longevity
Researchers report another longevity gene: "Scientists have previously found mutations that extend fruit fly lifespan, but this group of genes is distinct because it acts specifically in muscles. The findings could help doctors better understand and treat muscle degeneration in human aging. [Researchers] started investigating a pair of genes called "p38 MAP kinase" in fruit flies with the expectation that they could play a role in learning and memory. Along the way, they discovered that mutations in these genes speed up the process of aging and make the flies more sensitive to oxidative stress. ... It was really just dumb luck, because we found a mutant that had almost completely lost gene activity, but had enough activity to be born. ... If both genes are defective in the same fly, the flies die very early. ... The experiment that made us nervous was when we asked whether having more p38 could increase lifespan. You can make flies sick and shorten their lives in a hundred different ways easily, but finding one gene that makes a big change in lifespan is more significant. ... Fruit flies normally live about fifty days in [this] laboratory, depending on temperature and conditions. Some strains of fly that overproduce p38 MAP kinase live on average about 75 days, 50 percent longer than regular flies ... For this effect, it is sufficient that p38 is overproduced in muscles only. ... a protein that protects cells against oxidative stress that is found in mitochondria, superoxide dismutase (MnSOD), is responsible for at least some of p38 MAP kinase's effects on aging." That last point makes this look rather like the mouse studies in which life span was extended by genetic engineering to boost levels of natural antioxidants present in the mitochondria.
Accumulating the Groundwork for the Ultimate Cure for Cancer
It's good to be living at a time in which we can seriously discuss in some detail exactly how an ultimate cure for cancer would in fact be built: what biotechnologies are needed, how our biology would have to be changed. While we might all wish our births to have slid at least a few decades into the future to benefit from what will come, being here now puts us in a far better position than that of our immediate ancestors. Personally, I'd settle for the greatly improved odds of survival imparted by a very robust suite of cancer cures - and that is exactly what will emerge with the next generation of targeted cancer therapies that use some combination of immunotherapy and nanoscale engineering. Cancer doesn't worry me anywhere near as much as other aspects of aging, given the way the odds look to be shaping up. If you're two to three decades away from the prime years for cancer, then you should probably feel the same way.
In any case, one of the longer term research projects that is a part of the Strategies for Engineered Negligible Senescence (SENS) is the technical basis for what might be described as the ultimate cure for cancer. It goes by WILT, or Whole-body Interdiction of Lengthening of Telomeres. The short version of the idea is to turn off the ability of the human body to do the one thing that all cancers depend upon, which is lengthening telomeres beyond their normal limits. Telomeres are the protective caps at the end of chromosomes that progressively shorten with each cell division: one of their functions is to prevent runaway division of cells (i.e. cancer), but that roadblock can be evaded by a cancer that evolves any one of a number of ways to abuse mechanisms that the body normally uses to repair and lengthen telomeres in the few cell populations that need it.
The not inconsiderable downside of WILT is that a person who has undergone this treatment will have a reduced life span without access to procedures for regularly replacing their entire stem cell populations - turning off telomere lengthening will kill the possibility of cancer, but also put a short timer on the stem cells that need that process in order to keep repairing the body and replenishing cells. To my eyes this seems like an unnecessary risk when balanced against the future robustness of cancer therapies under development - but it's hard to argue against WILT as an ultimate cancer therapy.
That is, provided all of the scientific assumptions about WILT are correct. For example, that we know all of the biological processes by which telomeres can be lengthened, and that shutting them all down doesn't cause any other harm beyond the loss of stem cell longevity. So there is a certain amount of groundwork to be done to seal the case for WILT as ultimate-cancer-therapy-with-big-but-possibly-acceptable-downside, and the SENS Foundation has been funding some of it, whilst keeping an eye on other related research already ongoing. Here is an outline of one recent advance in knowledge:
To develop an unbreachable defense against cancer, SENS Foundation is pursuing the WILT (Wholebody Interdiction of Lengthening of Telomeres, or OncoSENS) strategy of preemptively deleting genes essential to the cellular telomere-maintenance mechanisms (TMM) from all somatic cells ... The strongest challenge to this approach, granting the periodic replenishment of somatic stem-cell pools with autologous but OncoSENS-ready stem cells, has been the possible existence of functions of TERT (telomerase reverse transcriptase - the catalytic subunit of telomerase), other than the lengthening of telomeres itself.
...
A careful test of the development of [mice engineered to lack TERT] would be expected to provide strong evidence on the subject one way or the other, provided that telomere lengths did not shorten excessively. Nobel laureate Dr. Carol W. Greider, whose career in telomerase research and path to the Nobel prize began when she first identified the enzyme in 1984, has finally carried out such a test, and she and her collaborators have generated results that strongly support the safety of this element of WILT.
...
This little-heralded, meticulous investigation into the effects of ablation of the telomerase catalytic subunit in mice with human-like telomeres provides us with strong reassurance that, should it prove to be the preferred approach for implementing the OncoSENS strategy, the effects of knocking out TERT would be limited to those dictated by the loss of telomere-lengthening per se, and would not lead to an unintentional loss of some essential but hitherto-unknown physiological function.
17
Oct
2011
FGF and Stem Cell Aging
Researchers are spending more time these days on the mechanisms by which stem cell populations decline with age - understanding the controlling processes that stop stem cells from working so well in later life will be the key to restoring their effectiveness. For example; "The aging process decreases tissue function and regenerative capacity, which has been associated with cellular senescence and a decline in adult or somatic stem cell numbers and self-renewal within multiple tissues. The potential therapeutic application of stem cells to reduce the burden of aging and stimulate tissue regeneration after trauma is very promising. Much research is currently ongoing to identify the factors and molecular mediators of stem cell self-renewal to reach these goals. Over the last two decades, fibroblast growth factors (FGFs) and their receptors (FGFRs) have stood up as major players in both embryonic development and tissue repair. Moreover, many studies point to somatic stem cells as major targets of FGF signaling in both tissue homeostasis and repair. FGFs appear to promote self-renewing proliferation and inhibit cellular senescence in nearly all tissues tested to date. ... The effects of FGF signaling can be in part attributed to the stimulation of self-renewal in endogenous somatic stem cells within these organs, but there is also much evidence that FGF signaling also plays a role in the concomitant inhibition of cellular senescence in stem cell. The evidence presented here also suggests a role of FGF signaling in the more committed cells downstream of stem cells, a role that appears to stimulate differentiation. Moreover, in most cell types studied, FGF seems to play a permissive role rather than a direct inductive or instructional role, usually by modifying the responsiveness of the cells to other factors or by potentiating and synergizing with other signals. That seems to hold true in both stem cells self-renewal and differentiation of more committed cells."
Another Large Study Shows No Benefit From Antioxidant Supplementation
The idea that you can do something positive for long term health by consuming presently available antioxidant supplements is a myth, not backed up by scientific evidence at all: "A study of vitamin E and selenium use among 35,000 men found that the vitamin users had a slightly higher risk of developing prostate cancer ... A separate study of 38,000 women in Iowa found a higher risk of dying during a 19-year period among older women who used multivitamins and other supplements compared with women who did not ... The findings are the latest in a series of disappointing research results showing that high doses of vitamins are not helpful in warding off disease. ... You go back 15 or 20 years, and there were thoughts that antioxidants of all sorts might be useful. There really is not any compelling evidence that taking these dietary supplements above and beyond a normal dietary intake is helpful in any way, and this is evidence that it could be harmful. ... Everyone needs vitamins, which are essential nutrients that the body can't produce on its own. But in the past few years, several high-quality studies have failed to show that high doses of vitamins, at least in pill form, help prevent chronic disease or prolong life." Antioxidants specifically targeted to the mitochondria have been shown to produce benefits to health and life span in mice, but running out to eat antioxidants from a bottle because of that is nothing more than magical thinking. In the case of currently available antioxidant supplements, there is every reason to think that they interfere with the beneficial mechanisms of exercise, causing a net loss in long term health.
The Skeptics and the Peripherally Interested
An unfortunate fact of life for anyone engaged in trying to persuade the world to adopt a new point of view - that crash development of rejuvenation biotechnology is a good and plausible idea, for example - is that people who are skeptical or only vaguely interested in your ideas don't tend to be vocal or engaged. So it's hard to assess their views in comparison to those people who have already been won over. This is simply a matter of priorities: when people take the time to publish their thoughts and lucid arguments, they tend to do so for their own causes, for the ideas they agree with. Time is, after all, fleeting - there are only so many blog posts and essays that can be written in any one life.
So as an advocate or activist, one has to pay attention to this hole in awareness; it's one of the things that makes advocacy a challenge. You're often none the wiser as to exactly how or why vast swathes of the population manage to be unresponsive to your message and outreach efforts. They know, but getting them to tell you is like blood from a stone.
On this topic, I see that Aubrey de Grey of the SENS Foundation recently gave a talk in Baltimore on SENS and the path to rejuvenation biotechnology. One of those attending was Kavan Peterson, a writer from ChangingAging, which is something of a pro-aging organization - both in the sense of empowerment and opposition to ageism, which are noble causes, but also in the less desirable sense of apologism for aging. There are already far too many talking heads trying to persuade the world that progressively accumulating pain, suffering, and loss of function are just fine and dandy. In any case Peterson, unlike most skeptics, took the time to write. So we should take the time to learn from that:
I am skeptical of de Grey's work and I'll use his own introduction to explain why: "It may seem premature to be discussing the elimination of human aging as a cause of death, when so little progress has been made in even postponing it says Aubrey de Grey." That's right - despite all the marvels of modern medical science, there is absolutely zero evidence that any known treatment has ever extended human life by a single day. Immortality is as fantastical an idea today as it was in ancient times.
I'd like to think of ChangingAging.org as the preeminent pro-aging blog so it was a great opportunity to talk to the world's leading anti-aging advocate. And surprisingly I came away with the impression that although our rhetoric is wildly divergent - as divergent as anti- vs pro-aging rhetoric can be - we share similar goals.
You should read the rest of it; this is an example of the type of person we'd like to persuade to support SENS and the broader field of work on repair-based strategies to reverse aging. Separately, I noticed another blog post from a different attendee, one who falls into the category of peripherally interested, I believe. She made this remark:
I asked the question: "There are assumptions in your theory, that the patient will get to the doctor on time, that the doctor is well trained in this new technology, and that the insurance companies will pay for these services." His answer was that his main focus is on the biological aspect and that these issues will come up and will need to be addressed at some point.
Also worth learning from.
14
Oct
2011
Explaining Divergent Levels of Longevity in High-Income Countries
This is an open access report in book format that delves into the factors that cause regional variations in life expectancy and rates of age-related disease - and thus longevity - in the first world. Given its origins, don't expect to see much on the stifling regulation that raises prices and reduces quality and innovation in medicine, but most of the other important contributing factors are addressed: "Over the past 25 years, life expectancy has been rising in the United States at a slower pace than has been achieved in many other high-income countries. Consequently, the United States has been falling steadily in the world rankings for level of life expectancy, and the gap between the United States and countries with the highest achieved life expectancies has been widening. International comparisons of various measures of self-reported health and biological markers of disease reveal similar patterns of U.S. disadvantage. The relatively poor performance of the United States with respect to achieved life expectancy over the recent past is surprising given that it spends far more on health care than any other nation in the world, both absolutely and as a percentage of gross national product. Motivated by these concerns, the National Institute on Aging requested that the National Research Council convene a panel of leading experts to clarify patterns in the levels and trends in life expectancy across nations, to examine the evidence on competing explanations for the divergent trends, and to identify strategic opportunities for health-related interventions to narrow this gap."
Another Interview with Sonia Arrison
From Next Big Future: "The [SENS5] conference itself was high quality - many of the scientists that I describe in my book, 100+, were there. Hearing about the tangible progress that these researchers are continually making was very exciting. I noticed that there were many companies that attended this conference, which is an indication that extending health span is a prospect which is starting to garner serious consideration. ... There are a large and growing number of corporations which, although not explicitly focused on anti-aging, are developing treatments and drugs related to longevity. Gene therapy and personalized medicine are the future, and these companies know that. ... The field of regenerative medicine is getting substantial resources. That includes tissue engineering, which is essentially growing organs. The recent successes with growing and implanting human tracheas are exciting. ... The most common concern is that increased life spans will lead to overpopulation. This fear rests on the false Malthusian idea that population grows faster than our ability to provide for ourselves. We haven't run out of resources as population has grown because humans are a resource themselves, providing problem-solving ideas. Also, fertility and world population growth rates are on the decline. ... Perceptions [of longevity science] have changed. The term health extension is actually less controversial than life extension, since everyone wants robust health. There is little resistance to treatments designed to keep people healthy."
A Comprehensive Summary of What is Known of Calorie Restriction and Longevity
Research into calorie restriction has, as I'm sure you know, been picking up in pace and breadth over the past decade or so. The drug industry is interested in trying to replicate the end results without the dietary changes, which should ensure continuing funds and interest for the foreseeable future. Lowering calorie intake while still obtaining optimal levels of micronutrients is a practice that, much like regular exercise, has long term beneficial effects on health and longevity in healthy animals and people. These benefits are very reliable and exceed those that can be provided by any presently available medical technology - they also exceed the results of many of the interesting ways to extend healthy life in laboratory animals. This state of affairs won't last, given the pace of progress in biotechnology, but based on the present landscape for medical development we should expect calorie restriction and exercise to remain the best available tools for most of us for a good twenty years yet.
I noticed a good open access review paper today (the full thing is in PDF format only) that covers all of what has been learned of calorie restriction (CR) in the past decade or two. That includes the results of a fair number of human studies, what is now known of the underlying biochemistry and mechanisms, differences between intermittent fasting versus constant dietary restriction (DR), and more:
CR has been demonstrated to extend the maximal lifespan of a diverse group of species. This extension of life is maximized when: 1) the magnitude of CR is elevated to the highest possible value before inducing malnutrition and 2) the duration of CR is maximized. Animals on CR regimens exhibit a variety of improvements in overall health in general and cardiovascular health in particular. Unfortunately, the likelihood of discovering whether or not CR extends human life is rather remote due to the ethical and logistical limitations of research design. The optimal magnitude and duration of CR for humans will also likely never be known for the same reason. Nonetheless, many human CR studies have noted favorable changes in biomarkers related to cardiovascular and glucoregulatory function, which likely relate to quality of life and may relate to longevity.
...
Regarding DR, neither carbohydrate restriction nor lipid restriction extend life. However, protein restriction appears to extend maximum lifespan by 20%. Recent findings suggest that methionine restriction may be the single cause of life extension observed in protein restriction studies. Future studies should examine the effects of different magnitudes of methionine restriction on life extension.
It's pessimistic to think that optimal calorie restriction practices will not be uncovered for humans, however. Scientists can measure changing levels in biomarkers over years of calorie restriction, so identifying optimal practices really rests on the larger area of work that relates to linking biomarkers with aging and longevity. If measurable aspects of our biology can be firmly linked to future life expectancy - and there is no reason to think that the development of such biomarkers is implausible - then a whole range of medical and health practices become open to far greater optimization than is presently possible.
13
Oct
2011
Making Old Beta Cells Act Young
Via EurekAlert!: "As a person ages, the ability of their beta cells to divide and make new beta cells declines. By the time children reach the age of 10 to 12 years, the ability of their insulin-producing cells to replicate greatly diminishes. If these cells, called beta cells, are destroyed - as they are in type 1 diabetes - treatment with the hormone insulin becomes essential to regulate blood glucose levels and get energy from food. Now, [researchers] have identified a pathway responsible for this age-related decline, and have shown that they can tweak it to get older beta cells to act young again - and start dividing. ... a protein called PDGF, or platelet derived growth factor, and its receptor send beta cells signals to start dividing via an intricate pathway that controls the levels of two proteins in the beta cell nucleus, where cell division occurs. Working with young mice, [researchers] found that PDGF binds to its receptor on the beta cell's surface and controls the level of these regulating proteins allowing cells to divide. However, in older mice, they discovered that beta cells lose PDGF receptors, and that this age-related change prevents beta cells from dividing. [Researchers] further found that by artificially increasing the number of PDGF receptors, they can restore the ability of the beta cell to divide and generate new cells. ... By understanding what genes are turned on and off in a young beta cell, we can try to recreate that genetic environment in older beta cells such that they divide in a desirable, controlled manner."
Naked Mole Rat Genome Published
Sequencing of the genome of the long-lived naked mole rat was announced earlier this year, but here's more: "Scientists have sequenced the complete genome of the naked mole rat, a pivotal step to understanding the animal's extraordinarily long life and good health. A colony of more than 2,000 naked mole rats at The University of Texas Health Science Center at San Antonio contributed to the findings ... If we understand which genes are different or are expressed differently in naked mole rats - compared to short-lived mice that clearly have poor defenses against aging and cancer - we might find clues as to why the naked mole rat is able to extend both health span and longevity, as well as fight cancer, and this information could be directly relevant and translatable to humans. ... The mouse-sized naked mole rat is the longest-lived rodent known, surviving up to 31 years in captivity. This is much longer than its laboratory rodent relatives, and the naked mole rat maintains good health and reproductive potential well into its third decade. Naked mole rats live underground in large family groups, like termites and bees, with only a single breeding female. These social rodents are extremely tolerant of life in low oxygen and high levels of carbon dioxide."
The Prospects for a Near Term Funding Desert
From where I stand, it looks much like the equities market has given the sign of doom over the past couple of months. The view of the next couple of years I subscribe to is that equities will fall dramatically some more very soon, then there will be a variety of massive government intervention timed to influence the presidential elections in 2012. The markets will then rise much as they did after the last massive intervention, but fail to regain the highs of this year, and thereafter fall into the pit through 2013. All of these equity market gyrations, like those of the past couple of years, are just a symptom of the deep underlying economic malaise in what was formerly a grand economic powerhouse - though malaise is probably the wrong word, as it suggests something that just happened, faultlessly. This is very much a state of affairs created through the actions of a comparatively small number of people in positions of power - evenly distributed between government and financial industries in a symbiotic state of regulatory capture - and then again by the actions of the rest of us in letting them do what they do, in failing to understand enough of economics to see cause and effect, and in failing to act to stop this process.
It's no great secret that the US is decaying; this is history unfolding as a procedural. The US is ever more rapidly becoming just another Europe, Japan, or pick your dysfunctional fascist-leaning (per the dictionary definition) economy of choice. The ending of empires that centralize economic and legislative power, develop a ruling class, grow their military, and debase their currency is pretty much written in stone - it's the details of the move from wealth enjoyed in freedom to authoritarian poverty that will surprise people in their nature and timing.
But in any case, what does the sign of doom in the markets mean for the next few years of research funding, and especially speculative research funding for efforts such as SENS? In my experience it means much the same as it does for raising funds to launch startup companies. This is to say that when the economy is in the doldrums, raising funds is very challenging - especially when the equity markets have just started on their way down in earnest and fear is rife. Funding agencies and investors pull back, either because they've suffered losses or because they have the luxury of waiting for a few years for better times.
To my eyes that makes the next few years the time to double down on raising funds from high net worth philanthropists. These are people who will be slowing their normal flow of deals and investment, but who have most likely not suddenly lost wealth in any meaningful way. There is an argument to be made that investments in early stage research made in the shadow of a falling market and economic destruction will be more effective on a dollar for dollar basis: there may be greater access to researchers and resources at lower prices due to a downturn in the normal state of their employment, for example.
One rather important item to take away from all this is that, like everyone else, I'm wrong about the market at least half the time. The fundamentals underlying modern national economies, and the US in particular, are truly terrible, however. If markets are up, it's because they're being propped up by the Federal Reserve, most recently by an uncharacteristically direct process that amounts to devaluation of the dollar and pumping newly created-from-nothing money into equities. I consider these large-scale manipulations to be something that cannot continue forever: the only goals they achieve are (a) political, keeping one faction or another in favor by providing the modern equivalent of bread and circuses in the form of high equities prices, and (b) personal in the sense that some of the ruling class become very wealthy in the course of carrying out these activities. They don't create wealth in any meaningful sense, only the hollow illusion of it. Eventually the cards must come crashing down and the hole will grow too large to be filled in by the standard model of government bailout. As they say, the trouble with other people's money is that you eventually run out of it.
So maybe the next few years will see the US equities indexes much lower than they are now, and the fundraising scene a desert. Maybe not, but I think it more likely than the alternatives. If you're in the business of raising funds, now is the time to be stacking away for the coming winter, and finalizing all the deals you can.
12
Oct
2011
Mitochondria, Aging, and State of Mind
Following on from an earlier consideration of state of the mind and how that may interact with the operation of metabolism over the long term to affect aging, here is a very readable open access paper that tries to draw lines between longevity, psychological factors, and mitochondrial biochemistry: "A central question concerning longevity remains: Why do some people live long whereas others die early? Another equally critical question concerns morbidity: Why is aging associated with a greater incidence of almost every categorized disease - including degenerative, metabolic, and malignant disorders? Since disease incidence, mortality, and longevity are all associated terms in the same aging equation, a more general question may be posed: What are the pathways that impact individuals' rate of aging? ... Compelling evidence suggests that both biological and psychosocial factors impact the process of aging. However, our understanding of the dynamic interplay among biological and psychosocial factors across the life course is still fragmentary. For example, it needs to be established how the interaction of individual factors (e.g., genetic and epigenetic endowment and personality), behavioral factors (e.g., physical activity, diet, and stress management), and psychosocial experiences (e.g., social support, well-being, socioeconomic status, and marriage) in perinatal, childhood, and adulthood influence health across the aging continuum. This paper aims to outline potential intersection points serving as an interface between biological and psychosocial factors, with an emphasis on the mitochondrion."
AGE Levels Correlate With Cognitive Decline
An accumulation of advanced glycation endproducts (AGEs) is one of the changes thought to be a root cause of aging. The research quoted below is only a correlation, but there is plenty more where this came from to back up the viewpoint of AGEs as a contributing cause of aging: "Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. ... We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. ... Older adults with high pentosidine level had worse baseline DSST score but not different 3MS score. On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile ... [Thus] high peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes."
Incremental Advances in Stem Cell Science are Constant and Ongoing
Somewhere in the world, someone today pushed out the boundaries of what can be done with stem cells in medicine. The field is now so large and well funded that noteworthy advances are rolling in every week, and for each incremental step forward that you read about in the popular science press there are another half a dozen more behind the scenes, achieved without much commentary outside the scientific community. This is what a healthy field of research and development looks like: a lot of movement, a great deal of progress. Here are pointers to a few recent items, representative of what is taking place day in and day out around the world:
The study found that a combination of two drugs lengthened survival time and prevented liver rejection in rodents. One drug was a low dose of tacrolimus, which prevented immediate rejection of the transplant, and the other was plerifaxor, which freed the recipient's stem cells from the bone marrow. The bone marrow cells freed by plerifaxor then traveled to the damaged liver and repopulated it with the recipients' own cells, replacing the donor cells that cause rejection. The stem cells also appeared to control immune response by increasing the amount of regulatory T-cells. Essentially, the scientists said they transformed the donor liver from a foreign object under attack by the immune system into an organ tolerated by the body within three months of the surgery. And - the rats only had to take the medications for one week after the transplant.
Researchers from the Wellcome Trust Sanger Institute have today announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate. Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors [retinoic acid receptor gamma (RAR-γ) and liver receptor homolog (Lrh-1)], Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.
Limbal stem cell deficiency (LSCD) [is] a condition which causes the cornea to become cloudy and develop a rough surface causing pain and leading to blindness. Currently, treatments focus on harvesting limbal cells from a patient's healthy eye or from cadaveric tissue. In her pioneering research, Dr. Meyer-Blazejewska considered the potential use of stem cells harvested from hair follicles to reconstruct damaged tissue for patients who suffer from LSCD in both eyes. ... Dr. Meyer-Blazejewska's team demonstrated that in the right microenvironment stem cells from hair follicles do have the capacity for cellular differentiation, the process whereby a less specialized cell becomes a more specialized cell type, in this case the cells of the corneal epithelial phenotype. The team's results showed an 80% rate of differentiation in mouse eyes following a cell transplant highlighting the promising therapeutic potential of these cells.
Next year, Pfizer Inc. and a clutch of British scientists hope to join a small but growing group of researchers conducting the first clinical trials in one of the more contentious areas of science: medical treatments derived from human embryonic stem cells. Pfizer and its partners at University College London's Institute of Ophthalmology are awaiting regulatory permission to begin a human study in the U.K. of a possible treatment for age-related macular degeneration, a common disorder in the elderly that can cause blindness.
The constant hum of progress from the field of stem cell science and development is what we'd like to see emerging from work on aging and longevity science - and needless to say we don't. There are not enough researchers, and there is not enough funding, and there is not enough popular support to build this sort of pace of progress at the present time. That is what we must strive to change.
11
Oct
2011
Hippocampal Neurogenesis in the Aged Brain
An open access paper: "Age-related changes in innate immune function and glial-neuronal communication are early and critical events in brain aging and neurodegenerative disease, and lead to a chronic increase in oxidative stress and inflammation, which initiates neuronal dysfunction and reduced synaptic plasticity, and ultimately disruption in learning and memory in the aged brain. Several lines of evidence suggest a correlation between adult neurogenesis and learning. It has been proposed that a decline in hippocampal neurogenesis contributes to a physiologic decline in brain function. Recently, new and important insights relating to the production of new neurons affecting hippocampal-dependent memory ability have been provided. A multitude of factors have been shown to regulate the production of new neurons in the adult hippocampus, many of which change as a result of aging. Yet, the potential importance of neurogenesis in some affective and cognitive behaviors, as well as endogenous tissue repair mechanisms, makes further investigation of neurogenic regulators warranted. We have recent evidence that key regulators of communication between neurons and microglia are disrupted in the aged brain and may be one of the factors that precedes and initiates the observed increase in chronic inflammatory state. In this review the role of dysfunction in these neuronal-glial communication regulators underlying age-related impairments in cognition and hippocampal neurogenesis will be discussed. An understanding of these mechanisms will lead to the development of preventive or protective therapies."
Pancreatic Cells Grown From Neural Stem Cells
From the New Scientist: "Beta cells in the pancreas produce insulin, which regulates glucose levels. People with diabetes either have type 1, in which native beta cells are destroyed by the immune system, or type 2, in which beta cells cannot produce enough insulin. To replace lost or malfunctioning beta cells, [researchers] turned to neural stem cells in the brain. First, they extracted a tiny amount of tissue from the rats' olfactory bulb, the part of the brain which deals with smell, or from the hippocampus, involved in memory. Each area is accessible through the nose, both in rats and humans. Next, the team extracted neural stem cells from the tissue and exposed them to Wnt3a - a human protein that switches on insulin production - and to an antibody that blocks a natural inhibitor of insulin production. After multiplying the stem cells for two weeks, they placed them on thin sheets of collagen which act as a removable scaffold. This allowed the team to lay the sheets incorporating the cells on top of the rats' pancreas without harming the organ itself. Within a week, concentrations of insulin in the blood of both type 1 and type 2 rats that had received treatment matched those in non-diabetic rats. Elevated blood glucose concentrations also returned to normal."
Can Character Traits Be Used to Predict Longevity?
Research into the physiology of psychological stress - how it changes the operation of metabolism and seems to accelerate some measures of aging - opens the door to asking whether other states of mind or character traits can affect human health and longevity in measurable ways. The difficulty of establishing measures of mental states makes this an unpopular topic for discussion in some reaches of the scientific community, and I'd be the first to say that a great deal of what passes for soft science these days is a waste of time and money. But there are physiological links between metabolism, aging, and the physical structure that forms the mind, so in the long run there should be some way to measure, assess, and correlate these links.
The just world hypothesis and how it may relate to health and longevity is easily stated. Individuals have a strong need to believe that they live in a world where people generally get what they deserve. The belief that the world is just enables the individual to confront his/her physical and social environment as though they were stable and orderly. Without such a belief, it would be difficult for the individual to commit himself/herself to the pursuit of long-range goals or even to the socially regulated behavior of day-to-day life.
Since the belief that the world is just serves such an important adaptive function for the individual, people are very reluctant to give up this belief, and they can be greatly troubled if they encounter evidence that suggests that the world is not really just or orderly after all. According to Lerner and Miller's just-world theory, people who believe that the world treats them fairly may plan confidently for their future, expecting their lives to be orderly, meaningful, and controllable, foreseeing a positive future or viewing one's living situation as justly deserved and hence fair. In turn, this expectation promotes mental health, meaning that the belief in a just world (BJW) can be seen as a "positive illusion". Indeed research links BJW to many indices of subjective well being including a greater purpose in life and commitment to planned healthy survival. There is empirical evidence showing that individuals who strongly believe in a just world have been seen to experience less stress and more positive affect than individuals with a weaker BJW.
The authors pull in data gathered from hundreds of study participants across the better part of a decade to support their hypothesis for this trait and a few others - including levels of distrust and the degree to which individuals see an open and expansive future ahead of them. The authors see definitive correlations between these comparatively narrow traits and mortality rates, and we might make guesses as to the mechanisms by which these correlations are established. Mechanisms similar to those linking stress with our biology, or more to do with the practice of good health over the years? The paper makes for interesting reading no matter your thoughts on whether this sort of research has any real merit.
10
Oct
2011
Mitochondria and Oxidative Damage in Aging
An open access review paper that covers some of the ground leading into the need for mitochondrial repair therapies to be a part of any comprehensive biotechnology toolkit capable of reversing aging: "Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by reactive oxygen species (ROS) is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age-related diseases."
Addressing the Environmentalists
The largest, most vocal and organized opposition to engineered longevity emerges from the environmentalist movement and their misguided view of resources and overpopulation. Here is a modest answer to those viewpoints: "Increased health and life spans may be a dream come true, but many worry that it could turn nightmarish owing to problems like overcrowding, resource depletion, and greater pollution. Living a long time might be wonderful on an individual basis, but if many people can do it, would the world still be a place in which we would want to reside? ... Consider the idea that more people automatically means less food for everyone. In reality, as population grew, so did our ability to produce food. Today, many around the world are struggling with obesity, or the consumption of too much food, all while the world's population has been growing. Since 1800, the price of wheat has been steadily declining and the daily intake of calories per capita in both the developed and developing countries has been on the rise. Though it may seem counterintuitive, greater numbers of humans do not necessarily translate to fewer available resources. A key reason for this is that the more people there are, the more ideas there are, and more ideas lead to new and better ways of producing the things that we need. Fiber optic cables, which turned out to be superior to copper as a conduit for data communications, were invented in response to prohibitively high copper prices. Analogous innovations have been engineered in the food industry, such as high-yield dwarf wheat that has saved countless lives in India and Pakistan, and crops that can flourish in areas with less pure or plentiful water. As the innovations driving the longevity revolution improve the length and quality of our lives, concurrent improvements in the environment can be expected. Numerous studies have shown that the less people have to focus their energy on survival and meeting their basic needs, the more they care about making their environment cleaner. This pattern has occurred, and continues to occur, in developed countries like the United States and is now beginning in developing countries."
In Search of Specific Epigenetic Predictors of Longevity
Just as the research community is sifting the world for correlations between variations in the human genome and variations in human longevity, so too are scientists beginning to pay greater attention to the role of the epigenome. The DNA in every one of our cells is better thought of as a whirling, dynamic machine rather than a static blueprint. It is in motion, a blur, a thousand thousand feedback loops involving the production of proteins that selectively alter the process of producing proteins. The amount of any one specific protein in a given cell produced from its DNA blueprint rises and falls dynamically, in response to environmental conditions, time of day, status of the cell's internal machinery, and a million other variations tuned by evolution. The epigenome is this dynamic partner to the static genome, a catalog of how genes become tagged and the changes that result from those tags. Epigenetics is the study of how DNA interacts with the machinery of protein construction to selectively modify the output in response to circumstances - and what that then means for cells, organs, and the operation of the body as a whole.
Just as there are genetic variations that subtly contribute to human longevity, we should expect there to be equally subtle epigenetic variations - though more complex, and harder to uncover. Research here contributes to the grand debate over the degree to which aging is programmed: is the epigenetic contribution to aging a matter of growing disarray in the processes of tagging and correcting levels of protein production, arising due to damage, or are there signs of programmed changes in levels of protein production that cause damage and dysfunction?
Why do some individuals live longer than others? ... Inter-individual variation in human longevity has not been found to be under substantial genetic control, with heritability generally between 15% and 30% ... The situation is thrown into relief in studies of C. elegans, in which genetically identical siblings reared in identical environments usually experience different lifespans. In this work, we show that physiological differences between identical animals begin to appear relatively early in life and that markers of ill health in young adulthood presage shorter lifespans.
Using fluorescent markers to examine the level of activation of several genes, we found three regulatory microRNA genes [in] which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA "biomarkers of aging" act upstream in insulin/IGF-1-like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan.
The educated guess at this point is that the way in which natural, unmodified life span emerges depends a little on the DNA blueprint, a lot on the environment, but just as much on chains of chaotic happenstance in the enormously complex operations of metabolism. We might consider that last line item a form of stochastic accumulation of molecular damage to cells: even with all other things being equal, individuals will age at somewhat different rates because initially small, localized differences in biological damage snowball over time into widely diverging system-wide outcomes.
Interestingly, it looks like there are good signposts on that road; we shall no doubt see how good or useful epigenetic biomarkers turn out to be in humans. Certainly a large community of researchers are hotly engaged in trying to uncover truly reliable biomarkers that measure aging or predict longevity, so if there is something to be found in the epigenome they will eventually find it.
07
Oct
2011
Examining an Unusual Data Set on Retirement and Longevity
It is the common wisdom that retirement from active work speeds the process of decline - and there are all sorts of reasonable explanations as to why this might be the case, but insofar as actual supporting evidence goes you're not going to find much of a consensus. That said, here is an unusual paper amongst those in search of a correlation between retirement and a shorter remaining life span: "Mortality hazard and length of time until death are widely used as health outcome measures and are themselves of fundamental demographic interest. Considerable research has asked whether labor force retirement reduces subsequent health and its mortality measures. Previous studies have reported positive, negative, and null effects of retirement on subsequent longevity and mortality hazard, but inconsistent findings are difficult to resolve because (1) nearly all data confound retirement with unemployment of older workers, and often, (2) endogeneity bias is rarely addressed analytically. To avoid these problems, albeit at loss of generalizability to the entire labor force, I examine data from an exceptional subgroup that is of interest in its own right: U.S. Supreme Court justices of 1801-2006. Using discrete-time event history methods, I estimate retirement effects on mortality hazard and years-left-alive. ... Estimates by all these methods are consistent with the hypothesis that, on average, retirement decreases health, as indicated by elevated mortality hazard and diminished years-left-alive. These findings may apply to other occupational groups characterized by high levels of work autonomy, job satisfaction, and financial security."
Sardinian Longevity and the Role of Exercise
Extreme Longevity notes an Italian study: "Sardinia [is] especially rich in male centenarians. The present study was undertaken to quantify and determine which particular lifestyle and nutritional variables endemic to Sardinia males accounted for their extreme longevity. The authors point out that no genetic differences have been found between Sardinian males and less long-lived males found elsewhere in Italy so they reasoned lifestyle choices were more likely causative of their longevity than genetic factors. The researchers specifically compared the frequency of several dietary choices and lifestyle factors between men of Sardinia and Italian men not from Sardinia. It was particularly surprising that diet alone didn't account for the differences. The frequency of meat, cheese, wine, grain and nut consumption was identical in the two groups. Total daily caloric intake was slightly but insignificantly lower in the Sardinian men. The most significant difference found was in the distance to work and average slope of the terrain between the men of Sardinia and those from other regions. The researchers conclude it is likely the large amount of daily physical exercise required to walk long distances up steep mountain climbs that has led to the increased longevity of Sardinian males. They point out the effect of physical exercise on extending longevity is becoming widely recognized, appearing at the conclusion of many scientific articles."
A Great Deal of What People Say About Radical Life Extension is Utterly Divorced From Reality
As I might have remarked upon back in the Fight Aging! archives, there is something about the idea of greatly extending human life through medical technology that sends otherwise sane people off the deep end. Mention the topic and you'll hear screeds on class warfare, relinquishment of progress in medicine, death before inequality, and visions of immortal tyrants lording it over mortal serfs. Nonsense, the lot of it, all utterly divorced from the history that shows us time and again exactly how change, even radical change, progresses in a technological society - but people say this stuff anyway.
there are a great many unrealistic viewpoints in the world that would hinder or halt longevity research, either directly or indirectly. Viewpoints like "the more regulation the better", "prove that you will do no harm at all before we'll let you move forward," or "let us redistribute all property and remove incentives for success and progress, for inequality for any is worse than death for all" spring to mind. In this latter context, "social justice" is a particularly pernicious phrase, being a shorthand for forceful redistribution of wealth by government fiat - institutionalized theft, aimed exactly at the point at which it will do the greatest damage to progress by removing incentives for success.
The world works this way: we can labor and trade to move everyone ahead, benefits for all and inequalities for all, or we can redistribute what presently exists - which at best leads to stagnation and no progress, and at worst becomes a repetition of Soviet era Russia and Eastern Europe. In both cases, inequality will be there - you can't kill it. The choice is whether it's inequality in comparative wealth or inequality in poverty, disease and rubble. Progress is absolutely dependent on freedom and the incentives of wealth earned through hard work and invention.
People react to the prospect of rejuvenation biotechnology in ways that are completely different from their reactions to, say, the highly effective next generation of cancer therapies. You don't hear people declaring that late stage treatments for cancer will split the world into warring factions of haves and have nots, or that all development must be halted until it can be offered to everyone. If you walk through all the varied nonsense spouted on the topic of society and radical life extension, and replace rejuvenation with stem cell heart therapies, or cures for cancer, or organs such as blood vessels grown to order - then you might start to see just how nutty it sounds. Medical technologies just as revolutionary have emerged in the past, and will continue to do so without being hoarded, restricted to the rich, tearing the world asunder, turning brother against brother, and causing cats to lie with dogs.
Could class conflict or even warfare break out over life-extension technologies? It is true that technology is rarely adopted by everyone at the same time, and when life-extending science hits the market, it will almost certainly be used by the wealthy first. ... New technologies are almost always adopted by the rich first, but over time they eventually reach everyone, and the historical record shows that the distribution of new technology is speeding up, not slowing down. For instance, it took forty-six years for one-quarter of the population to get electricity and thirty-five years for the telephone to get that far. It took only sixteen years, however, for one-quarter of American households to get a personal computer, thirteen years for a cell phone, and seven years for Internet access. A more vital example may be AIDS drugs which started off costing about $30,000 per patient per year 15 years ago. Now, better drugs are available and cost $100 per patient. ... The fact that the first users of life-extending technologies will tend to be wealthy increases the chances that the technologies will thrive and eventually reach everybody. Without private investors who believe in the value of a new product and want to support its development, many great ideas would be stillborn. History bears this out, from Queen Elizabeth owning some of the first silk stockings, to wealthy New Yorkers paying $20 in 1915 for a three-minute phone call to San Francisco.
I've long thought it rather sad that so much of our society is bludgeoned into the chattering classes' view of everything laid out in terms of class, conflict, redistribution, forced organization in a top-down fashion, and all the other unfortunate ideals that come with strong centralization of power. Their viewpoints are completely divorced from any sensibility as to how progress actually occurs, or how wealth is in fact created. They are thus one of the first barbarians hammering at the gate: people ignorant of the causes of the success of their society, yet still wealthy enough to be somewhat shielded from the immediate consequences of such ignorance. It never lasts forever, of course: in the end this will come to the same sorry end as Rome or the British Empire, and the US will become a shell of what it once was, a population living amidst the ruins of past grandeur, so constrained by their government as to have forgotten how to achieve greatness and prosperity once again.
The only silver lining is that scientific knowledge is no longer lost alongside the roots of wealth and prosperity; the world has become too small for that, and knowledge will move to the places where it can be best preserved. So those glories, at least, will continue even when the research community that produced them can no longer be sustained.
06
Oct
2011
Investigating Stem Cells and Spinal Cord Repair
Researchers continue to explore what stem cells might be able to achieve for the regeneration of serious injuries: "adult human mesenchymal stem cells may have an important role in the treatment and repair of spinal cord injuries. Mesenchymal stem cells (MSCs) are found mainly in the bone marrow and are the focus of many clinical trials that investigate potential methods of neurological repair and other regenerative applications. ...Although mesenchymal stem cells are widely known to be used in replacing damaged tissue, these stem cells may also recruit endogenous cells (those made within the body) to help accelerate the repair process. ... For the first time, [researchers] examined the use of human MSCs to prompt repair of spinal cord injuries in transgenic (genetically engineered or altered) zebrafish embryos. Zebrafish are especially valuable to researchers due to invertebrate characteristics that are similar to those of humans, the transparency of their bodies and their ability to initiate regeneration of damaged tissue. The study demonstrates that human MSCs affix to the injury site and influence spinal cord cells to accelerate the repair process. ... Our results indicate that MSC therapy not only augments recovery after spinal cord injury, but also accelerates the recovery time"
Targeted Nanoparticles Versus Brain Cancer
Via ScienceDaily: "Glioblastoma is one of the most aggressive forms of brain cancer. Rather than presenting as a well-defined tumor, glioblastoma will often infiltrate the surrounding brain tissue, making it extremely difficult to treat surgically or with chemotherapy or radiation. ... [scientists] developed a method to combine a tumor-homing peptide, a cell-killing peptide, and a nanoparticle that both enhances tumor cell death and allows the researchers to image the tumors. When used to treat mice with glioblastoma, this new nanosystem eradicated most tumors in one model and significantly delayed tumor development in another. ... This is a unique nanosystem for two reasons. First, linking the cell-killing peptide to nanoparticles made it possible for us to deliver it specifically to tumors, virtually eliminating the killer peptide's toxicity to normal tissues. Second, ordinarily researchers and clinicians are happy if they are able to deliver more drugs to a tumor than to normal tissues. We not only accomplished that, but were able to design our nanoparticles to deliver the killer peptide right where it acts - the mitochondria, the cell's energy-generating center. ... In this study, our patients were mice that developed glioblastomas with the same characteristics as observed in humans with the disease. We treated them systemically with the nanoparticles. Once the nanoparticles reached the tumors' blood vessels, they delivered their payload (a drug) directly to the cell's power producer, the mitochondria. By destroying the blood vessels and also some surrounding tumor cells, we were able to cure some mice and extend the lifespan of the rest,"
Cryonics Costs Money, Other Line Items Follow From That
Long-standing businesses must index everything they do to the changing - almost always falling - value of their regional currency, but very few smaller businesses do this in any sort of a deterministic way. Your average talented and determined fellow willing to start a company knows a lot about the business itself, but generally isn't very knowledgeable regarding currencies, inflation, finance, and so forth. That sort of expertise doesn't emerge in a company as a matter of course until it becomes much larger. So smaller businesses deal with the falling value of money by raising their prices as best they can on an ad hoc basis, but this is ever a challenge for products that involve very long memberships. Trying to raise rates on existing customers is, frankly, one of the hardest things a business can do. But raise rates they must, as modern paper currencies have long been set on a relentless spiral of devaluation.
This happens because politicians and government bureaucrats can use the strategic devaluation of their national fiat currency as a way to generate significantly more revenue for a given level of public upheaval than can be achieved through direct taxation - so of course they tend to do exactly that. This is why inflation exists, and is arguably why fiat currencies continue to enjoy such wide, legally-enforced use. So fiat currencies are somewhat systematically, somewhat opportunistically devalued over time in ways that result in a transfer of wealth from the public at large and into the control of politicians, bureaucrats, and their close supporters.
This is one of a number of processes that make long-term prognostication on future costs a challenge. Others include assumptions on the economies of scale that will emerge with success in development, or success in popularity of a product - successful products invariably become much cheaper as they become more widespread. This happens because competitors figure out more effective means of building the product, and because it is usually cheaper on a per-unit cost to build a hundred widgets rather than ten widgets.
The cryonics industry is presently running into a number of these issues. It offers products that are commonly paid for over decades, or where decades might elapse between the ink drying on a contract and the actual provision of service. The industry is decades old, but never grew to the point at which experience in managing the consequences of currency devaluation and other long-term strategic issues would naturally emerge amongst the major players in a field. At Alcor, this manifests as a growing underfunding issue, and to the credit of the present management they are openly publishing their current thinking on the matter:
The cryonics economies anticipated by Robert Ettinger in 1965 were never realized. By the 1970s, the cost of whole body cryopreservation as offered by TransTime and Soma (the for-profit arm of IABS, which later merged with Alcor) was $60,000. As shown in Fig. 1, the nominal dollar cost of cryonics has risen steadily with Consumer Price Index (CPI) inflation since then. By 2011, the minimum funding for whole body cryopreservation with Alcor was $200,000. Even this large number has not kept pace with inflation, so another increase will be necessary soon.
Whenever Alcor has increased cryopreservation minimums, it has traditionally only required new members to meet new minimum funding requirements. Existing members were "grandfathered," and allowed to remain members even if their cryopreservation funding fell below new minimums. This was and is believed to be important for members who due to age or disability become uninsurable, and would otherwise have to leave Alcor after many years of supporting the organization. ... However the main way that Alcor coped with grandfathering was by just taking the loss on what was historically a small number of underfunded cases. There was never a quantitative analysis of the impact of grandfathering, or a specific financial plan for dealing with it. ... The sustainability of this has been questioned on numerous occasions.
You should read the whole thing; it outlines the problem, puts numbers to it to show the size, and presents a range of possible solutions, along with discussion of their merits.
The bottom line is that businesses must act like businesses, even when they have their roots in the non-profit space, research, advocacy, and saving the world, as is the case for most of the ongoing cryonics concerns. There's no such thing as a free lunch, and the cost of providing a service has to be met somehow - if it isn't, then the whole product structure and relationship with the customer has to be rethought. The challenges of managing business agreements across decades have to be addressed by cryonics providers one way or another, such as by continually and clearly indexing against inflation for customers, or by using specialized financial instruments akin to futures contracts, as is the practice in many industries that have to make very long-term commitments and want to shield their customers from the complexity inherent in doing that.
In practice, things are always more complicated and intricate than the sweeping statements I give above, but I think an organization willing to put out a document that talks through their issues in this way is an organization with the right mindset to come to a solution. Openness is a virtue in this modern world, and I think that it is a very beneficial approach to customer relations when those relations have to extend across decades. Many of the most successful companies can be said to have communities as much as they have customers, and I don't see that as being a bad thing for the cryonics industry.
05
Oct
2011
Another Mitochondrial DNA Haplogroup Correlates to Longevity
MItochondrial function, structure, and damage are clearly important to longevity, both within and between species, so it should be no surprise to find mitochondrial DNAhaplogroups associated with variations in human longevity: "Human longevity is a complex heritable genetic trait. Based on substantial evidence from model organisms, it is clear that mitochondria play a pivotal role in aging and lifespan. However, the effects that mitochondrial genome variations have upon longevity and longevity-related phenotypes in Zhuang people in China have yet to be established. By genotyping 15 variants for 10 haplogroups in 738 Zhuang subjects, including 367 long-lived individuals and 371 controls, we found that haplogroup F was significantly associated with longevity in females of Zhuang population of China. Additionally, haplogroup F was related to higher HDL levels in long-lived individuals. Further analysis suggests that the non-synonymous variant m.13928G>C in haplogroup F was also associated with longevity in female Zhuang Chinese which might account for the beneficial effect of F."
Healthier and Wealthier
The Volokh Conspiracy on the correlations between health and wealth in a region, a connection with compelling evidence both before and after the Industrial Revolution: "for most of history, gains in human life expectancy were made at the beginning, not the end of life. It is true that older people have always been part of society, but they were less numerous and more weathered than today's seniors. ... But that is not the end of the story. Rather, it is the beginning of a new chapter where humanity takes on ill health and death at later ages. Indeed, those efforts have already had an impact on the growth of life expectancy. ... For many years, it's been clear that there is a positive correlation between health and wealth, but it was most commonly thought that wealth creates health. While it is certainly true that the rich can afford to take better care of themselves, it is now known that health also begets wealth. Put another way, poor health causes a decline in productivity for the simple reason that it's very difficult to work effectively when you're in ill health, thereby increasing the chances of falling into poverty. ... based on the available research, if there are 'two countries that are identical in all respects, except that one has a 5 year advantage in life expectancy,' then the 'real income per capita in the healthier country will grow 0.3-0.5% per year faster than in its less healthy counterpart.' While these percentages might look small, they are actually quite significant, especially when one considers that between the years of 1965 to 1990, countries experienced an average per capita income growth of 2% per year. When countries only have an average growth of 2%, an advantage of 0.5% is quite the boost. Now, those numbers are based only on a 5 year longevity advantage. What if a country had a 10, 20, or 30 year advantage? The growth may not continue on a linear basis, but if the general rule holds - a jump in life expectancy causes an increase in economic growth per capita - then having a longer-lived population would facilitate enormous differences in economic prosperity."
The Changing Understanding of Aging
I stumbled upon a series of open access review papers today, entitled "The Changing Understanding of Aging," written by a veterinarian for an audience of practitioners largely unfamiliar with the history and present state of aging research. As a consequence it's very readable for the layperson, and it really doesn't matter that the papers are as much focused on the animal kingdom as on human research: at the high level much of what is the case for the mammals we keep as pets is also the case for humans - the same theories apply. Only the details of our biochemistries are different, which does lead to greatly differing life spans and rates of aging, but all proceeding according to much the same fundamental mechanisms.
This second of three discussions about ageing biology and diseases continues at the level of the organism, examining the relationship among body composition, late life and diseases. ... Sarcopenia is declining mass and strength of skeletal muscle during aging. Healthy humans experience a 20%-40% reduced physical strength during decades 7 and 8. In one study, prevalence of sarcopenia among 883 elderly persons ranged from 13%-24% over the ages 65 to 70 and >50% after the age of 80. ... It is disconcerting that investigators have identified early skeletal muscle mass decline in some humans, with substantial change by decade five. Potential life span implications for individuals in this category need to be monitored by primary care and specialist physicians, and not just by geriatricians. Additional implications are that new studies need to be conducted to establish whether or how subtle mid-life changes in muscle mass and strength can be observed across animal species and what concerns accrue for their health and longevity.
A contentious debate revolves around whether ageing is purely a combined effect of stochastic events on residual programming relating to reproductive robustness, or whether ageing itself is programmed by natural selection. Emerging data indicate that the influence of genetic programming on specific late-life diseases, and even individual tissue pathologies, will probably need to be reconsidered in the light of newer theoretical possibilities.
04
Oct
2011
Alzheimer's as a Transmissible Disease?
An unpleasant conjecture outlined via EurekAlert!: "The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research ... Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease. The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's. ... Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease. ... We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain. The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure." It's probably best not to get too worked up about this sort of thing, concerning though it is. Many conditions can be made to be transmissible through the intervention of biotechnology, but that doesn't mean they are normally so in any meaningful way, and the prion diseases are not easy to transmit. The assumption at this point, based on the weight of evidence, should still be that Alzheimer's is something that in the vast majority of cases your body does on its own, and you bear a level of risk strongly associated with your lifestyle choices.
Making Myelin
From FuturePundit: "Myelin is insulation around nerves and is essential for the conduction of impulses along nerves. The ability to grow pure populations of cells that make myelin brings us closer to effective treatments for multiple sclerosis and other diseases characterized by the loss of myelin. ... Scientists [found] a way to rapidly produce pure populations of cells that grow into the protective myelin coating on nerves in mice. Their process opens a door to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases afflicting millions of people worldwide. ... These results matter to us all. Why? We all suffer from a demyelinating disease called aging. One of the reason older folks have harder times with memory recall, coordination, and other mental tasks is that myelin deteriorates with age. The ability to restore myelin is an essential rejuvenation therapy. Therefore the pursuit of effective treatments for MS and other demyelinating diseases will yield useful therapies for brain rejuvenation. Just about any therapy aimed at repairing damage caused by a specific disease will also be useful for rejuvenation. Aging causes very diffuse damage to all the tissues in the body. When enough of that damage accumulates in a single organ or structural element disease emanating from a specific location emerges. But the localized disease is really just part of a bigger pattern of damage accumulation. So therapies aimed at repair of specific locations in the body will have a great deal of overlap with therapies aimed at full body rejuvenation."
Big Money Actuarial Work as a Measure of Public Understanding of Longevity Science
People who make decisions involving very large amounts of money are not necessarily right any more often than the rest of us, but they do put in a great deal more groundwork and research in the course of making these decisions. In the gargantuan life insurance and pensions marketplace, where the long-term success of multinational conglomerates rests on good predictions of life expectancy, that amounts to a lot of time spent thinking about the near future of human longevity and medical technology.
The results of that work are not terribly secret. Industry mouthpieces update and publish the present consensus expectation for human life expectancy, as well as the consensus on the chances of that expectation being wrong, and the consensus on how large the errors might be. Then there are other analysts who watch the actions of various insurance and pensions giants in order to decide how that relates to what will happen to human life spans in the decades ahead - and on top of that, there are a whole range of big financial institutions that offer forms of insurance and risk management for the life insurance and pensions industry, trying to make money by better guessing the risk of error than other specialists.
I look on all this activity in two ways: firstly, it is a useful pathway for wider education on longevity science. The actuaries are aware of research and its implications long before the general public, and they are also hooked into business machinery that widely publishes their analysis and viewpoints. As a result, many people will be convinced about the prospects for engineered human longevity by the materials produced by the financial industry rather than those produced by patient advocates, scientists, and the medical industry.
Secondly, the work and publications of actuaries are a barometer for how compelling and widespread the arguments have become for significantly extending healthy human life through biotechnology. In this, I tend to pay attention to the pace at which their estimates are changing rather than the estimates themselves - it is my opinion that great financial upheaval lies ahead as sudden, large, and uncertain gains in life expectancy for older people are unlocked by advances in biotechnology. Present estimates are rather tied to the slow model of incidental life extension rather than the far more uncertain timeframe for the arrival of ways to achieve deliberate slowing and reversal of aging.
You might have a look at this recent article as an example of the sort of thing that catches my eye; the bigger picture of comparatively rapid changes in actuarial assessments is a good thing. It means that more people are paying attention to what is going on in the laboratory, and thinking clearly about what that means for the future.
The [UK's] biggest firms have increased their pensioner longevity assumptions for the fifth year running in a move which has added about 1% to scheme liabilities, Mercer says. Research from the consultant found FTSE100 companies had increased their UK longevity assumptions by about three months for current pensioners and by about five months for future retirees compared to the previous report in December 2009. It said, on average, male scheme members aged 65 are projected to live until 87.2, while those currently aged 45 who survive until 65 are expected to live until 89.2. Mercer said this represented an increase of about two years in life expectancy from its 2006 report - which means companies believe life expectancy has improved faster than previously expected, which has added to pension bills.
My suspicion is that anyone taking a large financial position that in effect depends on today's average 45-year-old dying on time in 2055 stands a good chance of losing their shirt. The guesstimate technologies of that decade veer into places that are hard to predict; it should be past the first business cycles of molecular manufacturing, for example, and at the same time benefit from fully mature technologies based on regenerative medicine, organ regrowth, and other forms of control over the body's cells and their state.
03
Oct
2011
Correlating Blood Vessel Damage and Cognitive Decline
An increasingweight of evidence links ongoing to damage to blood vessels in the brain with loss of cognitive ability as people grow older. Here is another example: "Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. ... For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. ... We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. ... Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning." The only practical, widely available ways to slow down blood vessel aging at the present time are exercise and calorie restriction, but future therapies - such as those built upon the SENS platform - will have to do better and actually reverse damage in the old.
The Popular Press on Actuarial Escape Velocity
Here's a popular press article that discusses the concept of actuarial escape velocity: "Someone you know could live to be 1,000 years old, according to Aubrey de Grey ... Even for people in good health, cells become damaged through the course of a human life, de Grey said. It's a solvable problem, he said, by providing maintenance to damaged cells. He cited stem cell research and using bacteria as possible means of restoring cells to their youthful state, which would lengthen life - perhaps infinitely. 'It's all about restoring organs and tissue to the way it was before it suffered some sort of damage,' he said, comparing the process to the maintenance that can keep cars running for decades.The research that could lead to these techniques is further along than most people realize, de Grey said, and could begin providing therapies within the next 25 years. Or not, he added, but the possibility exists that today's 20-somethings could be alive in 3011. Not only would they be alive, but they'd be able to live well, he said. The progress toward treatments that can provide such longevity will be incremental, though. The therapies that might exist in 25 years may restore a 90-year-old's body to a 60-year-old's health, but would not extend life indefinitely, he said. The key is reaching what de Grey called 'longevity escape velocity' - the rate of aging combined with the rate of the medical advancements that will prolong life to before-unthinkable lengths. An 80-year-old in 2011 hasn't much hope of living forever, he said, but the younger a person is, the better their chances of living in an age when drastically age-prolonging therapies exist
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eng
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ff8ca50c-6110-4f53-8776-cd4dd6e4afe2
|
https://www.fightaging.org/archives/2011/10/
| 4high
|
Abstract: We discuss some mathematical aspects of photon antibunching and sub-Poisson
photon statistics. It is known that Bell's inequalities for entangled states
can be reduced to the Cauchy-Bunyakovsky inequalities. In this note some
rigorous results on impossibility of classical hidden variables representations
of certain quantum correlation functions are proved which are also based on the
Cauchy-Bunyakovsky inequalities.
The difference K between the variance and the mean as a measure of
non-classicality of a state is discussed. For the classical case K is
nonnegative while for the n-particle state it is negative and moreover it
equals -n. The non-classicality of quantum states discussed here for the
sub-Poisson statistics is different from another non-classicality called
entanglement though both can be traced to the violation of the
Cauchy-Bunyakovsky
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eng
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ff2baec6-7587-4ab8-beab-037ec75eb43e
|
https://jp.arxiv.org/abs/1106.1892
| 4high
|
ABSTRACT
The structure and its immediate precincts in Mecca that also house a large mosque are referred to in the Qur'an and subsequently in Muslim tradition as the House of God (bayt Allah) and the sacred Mosque (masjid al hayam). The Ka'ba is the point of orientation for Muslims when they pray, and it is also the focal point of the Pilgrimage (Hajj) as well as the umra (minor pilgrimage). The Hajj takes place over a fixed period in the prescribed month, whereas the umra may be undertaken at any other time.
|
eng
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f69d173f-9f38-48e2-af05-6eea02d1fd44
|
https://www.taylorfrancis.com/chapters/mono/10.4324/9781315162447-11/-josef-meri?context=ubx&refId=290f2acb-ad21-4977-9529-cf2ed01c7f66
| 4high
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2022 Honda Civic | Serving the Columbia Area
2022 Honda Civic
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New 2022 Honda Civic
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eng
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76ce3617-77fa-42a8-bd89-767f610083c9
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https://www.midlandshonda.com/2022-honda-civic-columbia-sc/
| 2medium
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