[Updated: Out Of Stock In Spain] The Nexus 4 Is Back In Stock On Google Play In The UK, France, And Spain

Yesterday, Google re-released the Nexus 4 in the U.S., Germany, and Canada. We also heard that the UK, France, and Spain would be the lucky ones today. So far, everything seems to be panning out nicely, as both the 8GB and 16GB versions of the device ? as well as the bumper case ? just went on sale in the UK. We're still waiting to confirm availability in France and Spain.

Update: Just confirmed that it is indeed available in France and Spain, as well!

?

Update x2: Well, that was fast ? both the 8GB and the 16GB are already out of stock in Spain. Ouch:

8GB, 16GB, Bumper

Source: http://feedproxy.google.com/~r/AndroidPolice/~3/6SW3LD1YwpI/story01.htm

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Prince Charles and Camilla's surprise for London commuters

Commuters in London may have thought they had boarded the wrong train today when they saw who was sitting with them.

Traveling on the tube, London's subway, were none other than Prince Charles, the man next in line to the British throne, and his wife, Camilla, Duchess of Cornwall.

Charles and Camilla are usually driven around London privately, though Charles's son, Prince William, and his wife, Kate Middleton, have vowed to be more accessible, even doing their own grocery shopping.

The Prince of Wales and his wife only rode the train for a one-stop photo op to celebrate the London Underground's 150th anniversary.

READ MORE: Prince Charles Takes Over BBC Weather Forecast

Charles, 64, and Camilla, 65, spent a grand total of three minutes on the train, traveling on the Metropolitan line from Farringdon station to King's Cross, according to the UK's Telegraph. The trip was, according to British media, the first time the royals had traveled on the tube together and the first time Charles had been on the train since the 1970s, when he made another ceremonial appearance.

"Just one stop!" Charles said as they arrived at King's Cross, the UK's Guardian reported.

Despite their lack of experience, the pair managed to figure out how to swipe their "Oyster" fare cards in the turnstile to gain entrance, although they did have help in the form of a pre-loaded commemorative card.

Also helping Prince Charles and Camilla was a police escort keeping everyday passengers at bay, ensuring the royals each got a seat on the train for their short commute.

Also Read

Source: http://news.yahoo.com/blogs/abc-blogs/prince-charles-camilla-surprise-tube-passengers-203412913--abc-news-celebrities.html

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Google Currents (for Android)

Google can't stand to have users doing anything on other platforms, which is perhaps why it launched a free Flipboard (free, four stars) competitor called Google Currents for Android. After a fairly major update, the Currents app still isn't as social as Flipboard, but it's getting better and delivers a stylish, magazine-like reading experience on Android phones and tablets.

Flipping Through Currents
Users on Google Play have praised a recent update to Currents that changed the app's user interface. A hidden left tray, revealed by swiping to the right from the far left, shows several content categories such as business, news, lifestyle, etc. Each of these include subscriptions from major publications, including ABC News, Huffington Post, Popular Science, Saveur Magazine, Forbes, Fast Company, and others by default.

Select a publication, and you can scroll up and down through the stories. You can also select a category, and swipe left and right through? the various publications for more of an overview. Each category ends with a "breaking news" section, culled from Google News.

Most stories are visually appealing on Currents, with lots of space, pictures, and comfortably sized text. While browsing, categories are demarcated with a large, beautiful picture, while stories carry a headline, an image, and a blurb. Individual stories are paginated with a large image on the top, and you swipe or tap the left side of the screen to move through the story.

Be careful not to swipe too hard in a story, or you'll jump into the next in the publication. This quirk can be irritating, but Currents remembers your spot in each story so you can simply jump back into the one you left. On the plus side, it lets you quickly escape a dull article and jump into another.

Current's navigational paradigm feels a bit problematic at first. The ebook-style format for stories works for articles, and the combination horizontal and vertical scrolling works well for the higher-level view, but together they can be confusing. When I started with the app, I frequently lost my place, and kept panic-mashing the "back" button on the Galaxy S III.? After some getting used to it, though, the app feels quite natural.

Adding new publications is easy in Google Currents. A large plus sign on the top of the left-hand tray launches a new pane filled with recommendations, a search field, and categories with more publications. You can also add RSS feeds by searching for a URL. On the Currents website, you can subscribe to publications from a list, and if you're a publisher, access tools to get your media into the app.

A Flipboard Foe
While Google breaks subscriptions into categories, you add new subscriptions one at a time. This is a critical difference between Currents and Flipboard, which focuses more on adding broad, curated channels than media from publications, and could be a smart move on Google's part as it may give individual publications more exposure.

Some publishers do a better job adapting their content to the Currents platform than others. ABC News, one of the default publications, has beautiful, high-resolution images for each story. PRI, on the other hand, seems to favor low-res images, all of which look awkward and pixelated in Currents.

Flipboard and Currents also diverge sharply with social media. Both allow you to share stories to Twitter, Facebook, and even online storage services like Google Drive. Google, however, has no place for Twitter or Facebook within Currents. Flipboard treats the services like just another feed, so you can see Facebook updates and Twitter @ replies in your curated Flipboard magazine-esque content, for example. If you want familiar voices in your feed, Currents will leave you wanting.

You can also save stories for offline viewing in Google Currents, but that's almost not necessary. When the app starts up, Currents appears to immediately download the text for all subscriptions. I found that despite not being connected to a data network, the full text for stories still appeared, sans images. Flipboard, on the other hand, won't allow you to view anything but headlines without a data connection.

The Benefits of Google
One of the major benefits of Currents is that it's already part of Google. New users simply need to log in with their Google accounts and start reading.

Google attempted to leverage the success of its online RSS aggregator Google Reader into Currents but with mixed success. You can add RSS feeds from Reader by clicking the plus button at the top of the hidden left-hand navigation tray. Scroll all the way down, and you'll see a list of your RSS feeds from Google Reader.

Unfortunately, that's where synergies between the two services end. Read stories don't sync between Reader and Currents, meaning that you're effectively choosing one over the other. What's more, RSS feeds aren't like the purpose-created publications for Currents, and don't look nearly as nice. Some of them are just a paragraph with a link to the story online, and may not even have images.

Google leverages another of its technologies by adding a translate option. In the settings menu, users can designate a secondary language from a preset list from a list of over two dozen options. Users can switch language modes from the options menu, translating everything on the page (where available). Of course, if I am correct in assuming this is powered by Google Translate, who knows how accurate it is.?

Despite strong features, Google Currents for Android doesn't feel as focused or polished as Flipboard.? Google Currents has its own unique design, and is enjoyable to read, with nicely formatted articles from top-tier sources to draw you in. It fits seamlessly into your existing Google footprint (though perhaps not seamlessly enough, in the case of Google Reader). If you're a Flipboard user, and it works for you, stick with it. If you're looking for a new way to read the news on Android, flip through Currents.

More Android App Reviews:
??? Google Currents (for Android)
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Source: http://feedproxy.google.com/~r/ziffdavis/pcmag/~3/ibLJy9uTJP0/0,2817,2399864,00.asp

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Alternative Energy Transportation Still On The Rise - HybridCars.com

We keep hearing it, and numbers don?t lie: the market for hybrid-electric and alternative fueled vehicles is growing, and in a recent data mining exercise, Ward?s Auto commented on the continued expansion.

Most noteworthy perhaps, is from 2011 to 2012 a 64-percent spike in U.S. consumer sales of hybrids took place with sales, according to Ward?s data, of 427,605 units last year compared to 261,507 in 2011. (Actually, the HybridCars.com Dashboard according to numbers supplied by AutoData and Baum & Associates says 268,807 in calendar year 2011 and 434,498 in 2012, but we digress ?)

However you slice it, the alternative-tech market has been slowly advancing upwards for some time ? and with these vehicles now at around 3.3-percent share of the total U.S. market as Wards counts it, this means it still has a long way to go, but the pace of progress is picking up. Wards noted for the decade of 1999-2009, alternative-fueled vehicles as a segment grew to 2.8 percent, then spiked to the 3.3 they are at now.

As a segment furthermore, Wards observes hybrids sold better than ?all but a handful? of vehicle segments and this includes three SUV categories, small cross/utility vehicles and midsize luxury cars.

At this point, it seems like every global manufacturer is jumping into the hybrid and alternative energy pool, and this includes Europeans and Americans not to mention he Japanese and Koreans making alternative vehicles in all categories.

Some are mildly sprinkling in electrified or otherwise advanced-tech offerings to whittle down their average fleet economy numbers, others are showing they are more committed, and others, like Toyota and Infiniti, are aiming to have a hybrid variant of every model offered.

Terms like ?fun to drive? and ?high performance? are also being used to describe some alternative-fueled vehicles whose primary mission remains saving fuel and reducing emissions.

Given that electric motors can do for a gas or diesel engine what a turbo or supercharger can do ? add speed ? this is not so surprising. In the all-electric category, while most of the yet-few EVs are still just so-so speed-wise, Tesla is pushing the bounds, and has just set a record for production EVs in the quarter mile.

Beyond powertrain engineering, the chassis engineers and designers are also adding to the total package so mid-grade alternative-tech vehicles are offering far more satisfying driver experiences. Cars like the Camry Hybrid, or VW Jetta Hybrid demand no compromises in driver expectations just so they can be green.

And beyond hybrids, also adding to the growing alternative category are diesels. While the U.S. is far behind Europe in adopting them, they are coming along, which Autoblog also observed countering some of Ward?s analysis.

Autoblog noted of Ward?s observation of 2.8 to 3.3 percent growth of ?alternative fuel? vehicles that within this count were over 100,000 diesels sold by Audi and Volkswagen, and over 11,000 all-electric car sales.

This may be so, but we?re not quite so sure we can agree with Autoblog when it says ?All of that means that true hybrid market share was less than three percent for 2012 ? and closer to the 2009 levels ? despite having a much improved total volume in a much improved car market.?

Not to quibble, but we?ll just read the numbers from our our monthly Dashboard. It clearly says hybrids in calendar year 2012 accounted for 3.01 percent of all North American auto sales.

Again, this is a small market, and splitting hairs is not the aim here. The real take-away message is that consumer choice combined with broader selection by automakers, pushed also by looming government-imposed efficiency mandates is broadening the alternative energy transportation market.

We expect to see more growth, probably at a faster rate in coming years.

True, the respective ?alternative? segments yet represent a small minority. But they?ve paid a lot of dues, having been critically panned in cases as boring, frumpy, slow, quirky, and fraught with compromise. Many hybrids and alternative vehicles yet eek out miniscule numbers month after month, with the lion?s share of the sales volume being taken by other more standout performers.

While criticisms have had some merit, and as Autoblog observes, the market is ?still struggling? in a sense, that picture is changing, and alternative energy transportation is advancing.

It?s been a long enough wind-up period, but the underlying reasons remain as to why development of these alternative technologies were first embarked upon, including concerns over waning petroleum supplies, rising fuel prices, potential geopolitical instability, need for energy security, desire for reduction of greenhouse gases, and more.

So, despite the inertia still relegating alternative-tech to fringe status, and with more challenges yet to overcome, they appear to be on the rise with no slowing of the pace in sight.

Wards Auto, Autoblog

Source: http://www.hybridcars.com/alternative-energy-transportation-still-on-the-rise/

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Nexus 4 back on sale at German Google Play Store

Good news for anyone in Germany looking to track down a Nexus 4 -- the 8 and 16-gigabyte versions of the coveted handset are back on sale, with a 1 to 2-week estimated shipping time. As before, Germans can pick up the LG-made Nexus for €299 with 8GB of storage, or €349 with 16GB.

In other territories, including the U.S. and U.K., the phone remains sold out. However, LG has recently indicated that the supply situation should be improving towards mid-February, and says it's recently ramped up production of the phone.

More: Google Play Store

Source: http://feedproxy.google.com/~r/androidcentral/~3/8s-eEyOSUnQ/story01.htm

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Yoga Meditation Poses or Postures ? Yoga Lesson Ten - Health and ...

The purpose of yoga is to blend the spirit, mind and body, to achieve the end we must be balance physical, emotional and spiritual aspect of life. We can achieve this balance through meditation, breathing and yoga postures. Asana is yoga pose, posture, or position of the body that we adopt in yoga practice. Yoga requires determination and self-discipline in order to perform these asanas. Yoga stretches offer benefits to the mind and body and bring about balanced energy flow. There are numerous poses; we will discuss it one by one.

Meditation Poses.

Meditation Poses are preferred since these poses reduce the chance of going to sleep while meditation. ?Some of the meditation poses are as follows:-

• Padmasana (Full Lotus Posture)
• ?Ardha Padmasana (Half Lotus Pose)
• Egyptian Pose
• Burmese Pose

Padmasana (Full Lotus Posture)

Padmasana or Full Lotus Pose

Padmasana (Full Lotus Posture) is a cross-legged sitting posture, in this posture the feet are placed on the opposing thighs. ?It is an established posture, commonly used for meditation and the position is said to resemble a lotus. This posture is adopted to encourage proper breathing for associated meditative practice and to foster physical stability.

• Sit on the floor with your head and spine erect without sagging your shoulders. Keep your legs straight in front. Bend your right knee and bring the lower leg up into a cradle. Bend the right knee and bring the right ankle to the left hip crease with the sole of the right foot facing upwards. Settle the foot into the hip crease.
• Bend the left knee and cross the left ankle over to the right hip crease with the sole of the left foot facing upwards. Repeat, with the left foot on the bottom and the right foot on top.

  Tanum?nas? Meditaci?n en postura del Loto (Padmasana) (Photo credit: Wikipedia)

Benefits of Padmasana (Full Lotus Posture)

Benefits are as follows

• Allow the body to remain steady for long periods.
• Allows the mind to calm
• ?The posture applies pressure to the lower spine, which may facilitate relaxation.
• The breath can slow down
• Decrease in muscular tension and blood pressure.

Warning: If you feel uncomfortable or your body is not designed for this pose, do not force it. This may cause problems for you, carry out practice with any other pose.

Ardha Padmasana (Half Lotus Pose)

Ardha Padmasana (Half Lotus Pose)

Ardha Padmasana (Half Lotus Pose) is suitable for meditation. The Half Lotus Posture is a transitional pose for beginners who cannot sit at ease in the Lotus Posture (Padmasana). Yoga beginners can practice the Half Lotus Posture initially and change to the Lotus Posture later.

• Make a seated position and cross the legs.
• Place one foot on top of the opposite thigh.
• Place the hands on the knees. Touch the first finger with the thumb and extend the other fingers out. The hands can also be placed in front of the chest in prayer position for meditation.

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Source: http://healthinessbox.com/2013/01/29/yoga-meditation-poses-or-postures-yoga-lesson-ten/

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Stick Time: Home-Schooler in the Choir - ChoralNet

Date: January 28, 2013

by Scott Dorsey

Views: 353

Bring up the topic of home-schooling among a group of educators and you can be assured of a vibrant discussion.? A study by the National Home Education Research Institute (NHERI) estimates that in the spring of 2010, there were more than two million home-schooled students, K through 12.? That accounts for about four percent of our school-aged population.

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As choral music educators, we are eager to provide access to our art for as many students as possible within our respective schools.? How can a home-school student experience the same level of music education available to a child in a traditional educational environment?

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Among several possible ways to provide a choral music experience to home-school students is through a community youth choir.? There are many such excellent community youth choral programs in cities throughout the U.S.; including this choir ? the Concord Vocal Ensemble - featured at a recent ACDA Divisional Conference.

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Source: http://www.choralnet.org/view/409469

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Egypt army chief warns of collapse of state

CAIRO (AP) ? Egypt's army chief has warned of "the collapse of the state" if the political crisis roiling the nation for nearly a week continues.

The warning by Abdel-Fattah el-Sissi, also the defense minister, comes as the country sinks deeper into chaos and lawlessness. Attempts by the Islamist president to stem a wave of political violence appear to have made no headway.

Some 60 people have been killed in the unrest that began last Thursday.

El-Sissi's warning came in an address to military academy cadets on Tuesday. His comments were posted on the armed forces' official Facebook page.

"The continuation of the conflict between the different political forces and their differences over how the country should be run could lead to the collapse of the state and threaten future generations," he said.

Source: http://news.yahoo.com/egypt-army-chief-warns-collapse-state-090512430.html

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Increasing severity of erectile dysfunction is a marker for increasing risk of cardiovascular disease and death

Jan. 29, 2013 ? A large study published in PLOS Medicine on January 29, 2013, shows that the risk of future cardiovascular disease and death increased with severity of erectile dysfunction in men both with and without a history of cardiovascular disease. While previous studies have shown an association between ED and CVD risk, this study finds that the severity of ED corresponds to the increased risk of CVD hospitalization and all-cause mortality.

The study authors, Emily Banks (from the Australian National University) and colleagues, analyzed data from the Australian prospective cohort 45 and Up Study. The authors examined the association between severity of self-reported ED and CVD hospitalization and mortality in 95,038 men aged 45 years and older, after adjusting for a number of potential confounding factors. The study included more than 65,000 men without known CVD at baseline and more than 29,000 men with known CVD. There were 7855 incident admissions for CVD during an average 2.2 years of follow-up ending in June 2010, and 2304 deaths during an average of 2.8 years of follow-up, ending in December 2010.

The authors found that, among men without known CVD, those with severe versus no ED had a relative 35% increase in risk of hospitalization for all CVDs, and a relative 93% increased risk of all-cause mortality. Among men with known CVD at baseline and severe ED, their increased risk of hospitalization for all CVDs combined was a relative 64% and for all-cause mortality, 137%.

The researchers say: "The findings of this study highlight the need to consider ED in relation to the risk of a wide range of CVDs." They also stress that it is unlikely that ED causes CVD; rather both are caused by similar underlying causes such as atherosclerosis. As a result, ED could serve as a useful marker to identify men who should undergo further testing to assess their risk for CVD.

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The above story is reprinted from materials provided by Public Library of Science.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Emily Banks, Grace Joshy, Walter P. Abhayaratna, Leonard Kritharides, Peter S. Macdonald, Rosemary J. Korda, John P. Chalmers. Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study. PLoS Medicine, 2013; 10 (1): e1001372 DOI: 10.1371/journal.pmed.1001372

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/lfWEGp32NiM/130129130945.htm

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Marissa Mayer Details Her 3 Goals for Yahoo: More Users, Bigger International Reach And Broader Demographics

Considering the long-standing struggles of Yahoo as a business, its board of directors battles, and Scott Thompson's "ResumeGate", Yahoo (and its investors) have been in sore need of some good news. When beloved Google exec Marissa Mayer took the helm as CEO back in July, finally Yahoo had a cause for optimism. Today, Yahoo released its financial results for Q4 2012, which marked the end of Mayer's second full quarter at the helm and showed that new CEO's efforts to implement a turnaround are truly underway. For starters, the company showed the first signs of progress in that regard, with revenues coming in at $1.22 billion with non-GAAP EPS at 32 cents -- a 4 percent year-over-year increase.

Source: http://feedproxy.google.com/~r/Techcrunch/~3/TUPqQ3u1l4Y/

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Toward 2-D devices: Single-atom-thick patterns combine conductor and insulator

Jan. 27, 2013 ? Rice University scientists have taken an important step toward the creation of two-dimensional electronics with a process to make patterns in atom-thick layers that combine a conductor and an insulator.

The materials at play -- graphene and hexagonal boron nitride -- have been merged into sheets and built into a variety of patterns at nanoscale dimensions.

Rice introduced a technique to stitch the identically structured materials together nearly three years ago. Since then, the idea has received a lot of attention from researchers interested in the prospect of building 2-D, atomic-layer circuits, said Rice materials scientist Pulickel Ajayan. He is one of the authors of the new work that appears this week in Nature Nanotechnology. In particular, Ajayan noted that Cornell University scientists reported an advance late last year on the art of making atomic-layer heterostructures through sequential growth schemes.

This week's contribution by Rice offers manufacturers the possibility of shrinking electronic devices into even smaller packages. While Rice's technical capabilities limited features to a resolution of about 100 nanometers, the only real limits are those defined by modern lithographic techniques, according to the researchers. (A nanometer is one-billionth of a meter.)

"It should be possible to make fully functional devices with circuits 30, even 20 nanometers wide, all in two dimensions," said Rice researcher Jun Lou, a co-author of the new paper. That would make circuits on about the same scale as in current semiconductor fabrication, he said.

Graphene has been touted as a wonder material since its discovery in the last decade. Even at one atom thick, the hexagonal array of carbon atoms has proven its potential as a fascinating electronic material. But to build a working device, conductors alone will not do. Graphene-based electronics require similar, compatible 2-D materials for other components, and researchers have found hexagonal boron nitride (h-BN) works nicely as an insulator.

H-BN looks like graphene, with the same chicken-wire atomic array. The earlier work at Rice showed that merging graphene and h-BN via chemical vapor deposition (CVD) created sheets with pools of the two that afforded some control of the material's electronic properties. Ajayan said at the time that the creation offered "a great playground for materials scientists."

He has since concluded that the area of two-dimensional materials beyond graphene "has grown significantly and will play out as one of the key exciting materials in the near future."

His prediction bears fruit in the new work, in which finely detailed patterns of graphene are laced into gaps created in sheets of h-BN. Combs, bars, concentric rings and even microscopic Rice Owls were laid down through a lithographic process. The interface between elements, seen clearly in scanning transmission electron microscope images taken at Oak Ridge National Laboratories, shows a razor-sharp transition from graphene to h-BN along a subnanometer line.

"This is not a simple quilt," Lou said. "It's very precisely engineered. We can control the domain sizes and the domain shapes, both of which are necessary to make electronic devices."

The new technique also began with CVD. Lead author Zheng Liu, a Rice research scientist, and his colleagues first laid down a sheet of h-BN. Laser-cut photoresistant masks were placed over the h-BN, and exposed material was etched away with argon gas. (A focused ion beam system was later used to create even finer patterns, down to 100-nanometer resolution, without masks.) After the masks were washed away, graphene was grown via CVD in the open spaces, where it bonded edge-to-edge with the h-BN. The hybrid layer could then be picked up and placed on any substrate.

While there's much work ahead to characterize the atomic bonds where graphene and h-BN domains meet and to analyze potential defects along the boundaries, Liu's electrical measurements proved the components' qualities remain intact.

"One important thing Zheng showed is that even by doing all kinds of growth, then etching, then regrowth, the intrinsic properties of these two materials are not affected," Lou said. "Insulators stay insulators; they're not doped by the carbon. And the graphene still looks very good. That's important, because we want to be sure what we're growing is exactly what we want."

Liu said the next step is to place a third element, a semiconductor, into the 2-D fabric. "We're trying very hard to integrate this into the platform," he said. "If we can do that, we can build truly integrated in-plane devices." That would give new options to manufacturers toying with the idea of flexible electronics, he said.

"The contribution of this paper is to demonstrate the general process," Lou added. "It's robust, it's repeatable and it creates materials with very nice properties and with dimensions that are at the limit of what is possible."

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The above story is reprinted from materials provided by Rice University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. C. Drexler, S. A. Tarasenko, P. Olbrich, J. Karch, M. Hirmer, F. M?ller, M. Gmitra, J. Fabian, R. Yakimova, S. Lara-Avila, S. Kubatkin, M. Wang, R. Vajtai, P. M. Ajayan, J. Kono, S. D. Ganichev. Magnetic quantum ratchet effect in graphene. Nature Nanotechnology, 2013; DOI: 10.1038/nnano.2012.231

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_science/~3/Z5aTSo83LOQ/130127134208.htm

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In breast cancer metastasis, researchers identify possible drug target

Jan. 27, 2013 ? The spread of breast cancer to distant organs within the body, an event that often leads to death, appears in many cases to involve the loss of a key protein, according to UC San Francisco researchers, whose new discoveries point to possible targets for therapy.

In the January 27, 2013 online edition of Nature Cell Biology, UCSF scientists describe for the first time how the protein, known as GATA3 -- which is abnormal or absent in many cases of human breast cancer -- normally acts downstream in biochemical pathways to prevent the distant spread of cancer, an event called metastasis.

The discovery points to a biochemical control point that simultaneously holds in check several key events required for tumor cells to successfully spread.

"When GATA3 is present, it turns off many genes that are active in metastasis," said Zena Werb, PhD, a UCSF professor of anatomy who led the research. "We now have identified the molecular mechanisms involved."

The key finding of the new study is that GATA3 acts downstream biochemically to activate a molecule -- obscure until now -- called microRNA29b. MicroRNA29b in turn stops protein production from other genes that play vital roles in metastasis.

The absence or loss of GATA3 can free cancerous cells to break free from their defined roles and tethers within a tumor, to move away from the tumor mass, to induce cancer-promoting inflammation, and to stimulate the development of new blood vessels that can help spreading cancerous cells regrow as tumors in new locations.

"People knew that some of these genes were turned on in some cancers, but they did not know they were turned on because GATA3 and microRNA29b were turned off," Werb said. "If you have 20 genes that are becoming less active all at once due to microRNA29b, it could have a profound effect."

Working with mice, the researchers found that restoring microRNA29b to one of the most deadly types of breast cancer stopped metastasis. But the researchers also found that if they knocked out the microRNA29b, tumors spread even in the presence of GATA3, suggesting that microRNA29b can be the driver of metastasis.

In the mouse models of breast cancer studied by Werb's team, GATA3 normally restrains cancerous cells from breaking away from the main tumor and migrating to other organs.

It might be possible, Werb said, to develop drugs that inhibit breast cancer metastasis by re-activating these controls in cancerous cells that have lost the normal protein.

Many researchers who study early stages of cancer focus on abnormal genes and proteins that cause cells to expand their numbers rapidly, a hallmark of cancer.

However, the ability to spread to distant places and to eventually cause lethal complications requires not only cell division and tumor growth, but also changes in how the cancerous cell negotiates with its surroundings. This relationship must be altered to permit cancer to spread, according to earlier research findings by Werb and others.

"Many of the key processes in cancer that GATA3 suppresses take place outside the cell, in the surrounding environment," she said.

GATA3 is a master control for luminal cells, which line the milk-carrying ducts of the breast. In essence, GATA3 dictates the defining characteristics of a normal breast cell, Werb said.

Luminal breast cancers are the most common form of the disease, and the hormones estrogen and progesterone drive their growth. Loss of the normal GATA3 protein as luminal breast cancers evolve is associated with a greater risk of death, Werb said, and occurs in roughly 10 percent of luminal breast cancer cases.

But, along with many other proteins, GATA3 also is absent in "triple negative," breast cancers, which are more often fatal. Triple negative breast cancers, which disproportionately affect black women and younger women, do not depend on the hormones, nor do they require a third growth factor, called HER2.

Triple negative breast cancers, which account for roughly one-in-five breast cancers, have been more difficult to target successfully with newer treatments.

"The targeting we would like to do is to give back microRNA29b specifically to breast tumor cells to prevent metastasis," Werb said.

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The above story is reprinted from materials provided by University of California - San Francisco, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/9MKEP8kbDFI/130127134214.htm

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A roundup of the best photos of the day

Protesters chant slogans during a protest demanding the release of Lebanese leftist militant George Abdallah, who has been imprisoned in France for almost 30 years, outside the French embassy, while Lebanese policemen secure the area in front of the embassy, in Beirut January 28, 2013. The French government postponed the trial for the release of Abdallah till February 28. REUTERS/Sharif Karim (LEBANON - Tags: POLITICS CRIME LAW)

Protesters chant slogans during a protest demanding the release of Lebanese leftist militant George Abdallah, who has been imprisoned in France for almost 30 years, outside the French embassy, while Lebanese policemen secure the area in front of the embassy, in Beirut January 28, 2013. The French government postponed the trial for the release of Abdallah till February 28. REUTERS/Sharif Karim (LEBANON - Tags: POLITICS CRIME LAW)

Source: http://news.yahoo.com/photos/photos-of-the-day-1340925511-slideshow/

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How to Use Customer Service to Win the Customer | Business 2 ...

When it comes to good customer service, it seems like now more than ever, every business across every single industry is re-focusing on it, and prioritizing customer service ahead of all other issues.

That makes sense, of course, as businesses are under the gun now more than ever when it comes to dealing with and interacting with customers.

But with an increased focus on customer service generally across almost any industry, how can you be sure to get the most out of your customer service issues, and build your reputation as a company and brand that cares about winning the customer over with amazing service and support? Here are just a few ways to win the customer ? every single time ? and be sure that your business is a leader when it comes to customer service across the board.

Use Social Media To Win The Customer Over

When it comes to winning the customer, social media can be your biggest asset. Social media accounts allow customers to complain or praise about companies who have served them recently, but it?s all a two-way street. That is, you can also reach out back to the customer to find out how you can best help and serve them, and what you can do to improve their experience top to bottom when it comes to winning them over and proving your mettle to them.

Social media allows you to create an amazing customer service profile that can help build your business reputation, win over customers and potential clients, and expand your services top to bottom as you make a name for yourself in any industry or niche.

Make Yourself One-For-One With Each Customer

When it comes to truly winning over every single customer, issues start and end with seeing each customer as a person and a human, first and foremost, and as a customer with profit on the mind second (if at all). The best way to win the customer is to see them and their issue in front of you as the only issue that matters to you and your business; doing so provides the opportunity to better deal with them and their needs each and every day, regardless of what may come up.

Plus, when you see each customer as your only issue and problem, it makes it more likely that you will see each customer as the only customer you need to focus on and work with, increasing the chances you have of adequately and positively assisting and improving their issue or condition. This, in turn, makes your business the go-to company in your niche when it comes to dealing with and providing service for a wide variety of customers.

Prioritize what you do for your customers

Remember, winning the customer means focusing specially on each customer, one at a time, to ensure that you and they get the most out of your relationship and transaction, and that you can build relationships to develop a long-lasting customer and loyal client base to keep returning to you for years to come!

Source: http://www.business2community.com/customer-experience/how-to-use-customer-service-to-win-the-customer-0384058

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Obama asks police to help pass gun legislation

WASHINGTON (AP) -- President Barack Obama on Monday turned to law enforcement leaders in three communities with mass shootings for help in getting Congress to pass tough new gun legislation.

At a White House meeting, Obama said that no group is more important in the gun debate and he said he recognizes the issue "elicits a lot of passion all across the country." But Obama also said he believes Congress will respond to appeals from police.

"Hopefully if law enforcement officials who are dealing with this stuff every single day can come to some basic consensus in terms of steps that we need to take," he said, "Congress is going to be paying attention to them, and we'll be able to make progress."

The president's meeting comes as he tries to build support for gun control legislation that will be difficult to get through Congress. He urged Congress to pass an assault weapons ban, limit high capacity magazines and require universal background checks.

Obama met in the Roosevelt Room with the heads of the Major Cities Chiefs Association and the Major County Sheriffs Association, members of his Cabinet and chiefs that responded to the worst shootings of 2012. That includes Aurora, Colo., where 12 were killed in July; Oak Creek, Wis., where six died in a Sikh temple assault: and Newtown, Conn., scene of the most recent mass tragedy that left 20 first-graders dead.

Obama also said that Washington needs to take mental health issues and school safety more seriously and should help law enforcement agencies hire more police, make sure they get the training they need and give rural forces the resources they need to deal with emergencies.

"Many of them also recognize that it's not only the high profile mass shootings that are of concern here," the president said. "It's also what happens on a day in day out basis in places like Chicago or Philadelphia where young people are victims of gun violence every single day."

Source: http://news.yahoo.com/obama-asks-police-help-pass-183056466.html

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Movies Really Hate Math

If you were judging math by how Hollywood movies describe it, you'd wonder why it even exists. Like Nazis and dogfighting, math is universally hated. Just look at this supercut of movies talking about math. Nobody even wants to bother with two plus two! More »

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/mOg2joy7Eus/movies-really-hate-math

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Spanish newspaper sorry for 'false photo' of Venezula's Chavez

MADRID/CARACAS (Reuters) - Spain's influential El Pais newspaper apologized on Thursday for splashing a "false photo" of Venezuela's cancer-stricken leader Hugo Chavez on its front page, prompting a furious response from the government in Caracas, which vowed to take legal action.

Within minutes of posting the image online as a global exclusive, El Pais said it had discovered from social media that the photo was not of Chavez. It removed it from its website and withdrew its print edition.

Venezuela's government said the publication of the photo - which showed the head of a man lying down with a breathing tube in his mouth - was "grotesque," while Argentinian President Cristina Fernandez, a close ally of Chavez, called it vile.

"El Pais apologizes to its readers for the damage caused. The newspaper has opened an investigation to determine the circumstances of what happened and the errors that were committed in the verification of the photo," the paper said.

Chavez, 58, is fighting to recover in Cuba after undergoing his fourth cancer operation in just 18 months. He has not spoken or appeared in public for six weeks, fuelling speculation about how serious his condition is.

El Pais, one of the world's biggest Spanish-language publications and an institution both in Spain and in Latin America, said it received the grainy image from the agency Gtres Online, which it said represents 60 other agencies in Spain.

In a statement, El Pais said the newspaper was told it had been taken seven days earlier by a Cuban nurse who was part of Chavez's medical team, and was then sent to the nurse's sister, who lives in Spain.

"The agency has acknowledged it was deceived by those who provided the material and will take legal action," El Pais said.

The photo was on the newspaper's website for half an hour and also appeared in early editions of the print version that were then pulled from newsstands and replaced with a new edition with a different front page.

In Venezuela, anxious Chavez supporters and opponents alike are waiting for any new picture, video or audio message from the socialist leader, who is famed for filling the airwaves with long-winded speeches, jokes and withering jabs at his foes.

NO SIGHT OF CHAVEZ

Officials say his condition is improving after he suffered multiple complications, including unexpected bleeding and a severe respiratory problem following the December 11 surgery.

But, in contrast to Chavez's previous visits to Havana, officials have not published any evidence of his condition. In 2011, with great fanfare, they broadcast video footage of him reading a newspaper, walking in a garden, and chatting with his friend and mentor, Cuba's ex-leader Fidel Castro.

In the absence of such proof this time, many Venezuelans are questioning the terse official bulletins and suspect Chavez's extraordinary 14 years in power could be coming to an end.

The president has never said exactly what type of cancer he has, only that the initial tumor found in mid-2011 was in his pelvic area and was the size of a baseball.

Venezuelan opposition leaders have long accused the government of secrecy over his illness, while supporters accuse "bourgeois" local and foreign media of being in league with the opposition to spread rumors he is at death's door.

The handling of information relating to Chavez's health has become as contentious as the man himself, and his administration's updates have been confusing and contradictory.

The government says it has never been more transparent. It described El Pais's publication of the picture - a screengrab from an unrelated 2008 video - as part of efforts by far-right political forces to attack Chavez's self-styled revolution.

It said it would take appropriate legal action, and that the newspaper's apology to its readers was not enough.

"Neither their disgusting photos nor their systematic campaigns will stop the president's advance," Information Minister Ernesto Villegas told a news conference in Caracas.

"Would El Pais publish a similar photo of a European leader? Of its director? Sensationalism is valid if the victim is a revolutionary 'sudaca'," he added, using a pejorative term that is sometimes used in Spain to refer to Latin Americans.

(Editing by Eric Walsh)

(This story was refiled to correct the spelling of Venezuela in the headline)

Source: http://news.yahoo.com/spanish-newspaper-sorry-false-photo-venezulas-chavez-021829277.html

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Good Reads: Boomtown slum, democracy in progress, and 'rewilding' in the Netherlands

This week's good reads include a day in Kenya's bustling Kibera slum, the struggle to promote democracy in the Arab world, and a radical conservation theory in the Netherlands.

By Allison Terry,?Correspondent / January 7, 2013

A hairdresser braids a woman?s hair in her salon in Kenya?s Kibera slum.

Noor Khamis/Reuters

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The image of an African shantytown does not usually conjure up hope for economic prosperity. But Kibera, one of Nairobi?s slums and arguably Africa?s largest slum, is exactly that for the Kenyans who call it home. In The Economist, a writer chronicled a day in Kibera, describing the slum?s ebbs and flows, capturing its entrepreneurial spirit. People from all over Kenya leave their towns and villages for a chance to find work in Kibera?s ?thriving economic machine.?

Skip to next paragraph Allison Terry

Allison Terry is national news intern for the Christian Science Monitor. She previously worked on the cover page desk and contributed to the culture section of the Monitor.

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The half-mile-by-two-mile area accommodates roughly 1 million people, wedged together in repurposed wood-and-corrugated-tin-roof structures. The alleys that wind through the slum vary in size, but there is no room for cars. Many of the residents work in nearby factories or offices. Others find economic opportunity in providing goods and services for Kibera?s residents.

When Cecilia Achieng moved to the slum, she started a school, at first renting space from an empty church. She eventually saved enough money to build six makeshift classrooms. After school, Ms. Achieng starts her second job: catering. She caters church events, funerals, and is even trying to get into weddings. In the evening, Achieng goes door to door offering her services as a hairdresser.

?To equate slums with idleness and misery is to misunderstand them,? the correspondent writes. ?Slums are far from hopeless places; many are not where economic losers end up, but rather reservoirs of tomorrow?s winners.?

The promise of the Arab Spring

As post-Arab Spring countries struggle to establish democratic institutions, pessimism about their ultimate success misses a broader lesson: Stable democracies have historically evolved from violent uprisings, initial failures, and stumbling blocks.

?These troubles ... are not a bug but a feature ? not signs of problems with democracy but evidence of the difficult, messy process of political development through which societies purge themselves of the vestiges of dictatorship and construct new and better democratic orders,? writes Sheri Berman in Foreign Affairs.

Critics who see Egypt, Libya, and other transitioning countries as democratic failures ignore the inherited social, cultural, and political dynamics in these countries, and a broader historical perspective. New democracies are not blank slates, writes Ms. Berman. In the aftermath of overthrowing dictators, countries must overcome the baggage that comes with authoritarian regimes ? distrust, animosity, and lack of civil organizations to deal with people?s demands. Islamism is filling that void in Egypt after Hosni Mubarak?s fall as religious organizations were the only places where people could participate and express themselves.

Source: http://rss.csmonitor.com/~r/csmonitor/globalnews/~3/LGGtcHWW-GE/Good-Reads-Boomtown-slum-democracy-in-progress-and-rewilding-in-the-Netherlands

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Scientists discover how epigenetic information could be inherited

Friday, January 25, 2013

New research reveals a potential way for how parents' experiences could be passed to their offspring's genes. The research was published today, 25 January, in the journal Science.

Epigenetics is a system that turns our genes on and off. The process works by chemical tags, known as epigenetic marks, attaching to DNA and telling a cell to either use or ignore a particular gene.

The most common epigenetic mark is a methyl group. When these groups fasten to DNA through a process called methylation they block the attachment of proteins which normally turn the genes on. As a result, the gene is turned off.

Scientists have witnessed epigenetic inheritance, the observation that offspring may inherit altered traits due to their parents' past experiences. For example, historical incidences of famine have resulted in health effects on the children and grandchildren of individuals who had restricted diets, possibly because of inheritance of altered epigenetic marks caused by a restricted diet.

However, it is thought that between each generation the epigenetic marks are erased in cells called primordial gene cells (PGC), the precursors to sperm and eggs. This 'reprogramming' allows all genes to be read afresh for each new person - leaving scientists to question how epigenetic inheritance could occur.

The new Cambridge study initially discovered how the DNA methylation marks are erased in PGCs, a question that has been under intense investigation over the past 10 years. The methylation marks are converted to hydroxymethylation which is then progressively diluted out as the cells divide. This process turns out to be remarkably efficient and seems to reset the genes for each new generation. Understanding the mechanism of epigenetic resetting could be exploited to deal with adult diseases linked with an accumulation of aberrant epigenetic marks, such as cancers, or in 'rejuvenating' aged cells.

However, the researchers, who were funded by the Wellcome Trust, also found that some rare methylation can 'escape' the reprogramming process and can thus be passed on to offspring ? revealing how epigenetic inheritance could occur. This is important because aberrant methylation could accumulate at genes during a lifetime in response to environmental factors, such as chemical exposure or nutrition, and can cause abnormal use of genes, leading to disease. If these marks are then inherited by offspring, their genes could also be affected.

Dr Jamie Hackett from the University of Cambridge, who led the research, said: "Our research demonstrates how genes could retain some memory of their past experiences, revealing that one of the big barriers to the theory of epigenetic inheritance - that epigenetic information is erased between generations - should be reassessed."

"It seems that while the precursors to sperm and eggs are very effective in erasing most methylation marks, they are fallible and at a low frequency may allow some epigenetic information to be transmitted to subsequent generations. The inheritance of differential epigenetic information could potentially contribute to altered traits or disease susceptibility in offspring and future descendants."

"However, it is not yet clear what consequences, if any, epigenetic inheritance might have in humans. Further studies should give us a clearer understanding of the extent to which heritable traits can be derived from epigenetic inheritance, and not just from genes. That could have profound consequences for future generations."

Professor Azim Surani from the University of Cambridge, principal investigator of the research, said: "The new study has the potential to be exploited in two distinct ways. First, the work could provide information on how to erase aberrant epigenetic marks that may underlie some diseases in adults. Second, the study provides opportunities to address whether germ cells can acquire new epigenetic marks through environmental or dietary influences on parents that may evade erasure and be transmitted to subsequent generations, with potentially undesirable consequences."

###

University of Cambridge: http://www.cam.ac.uk

Thanks to University of Cambridge for this article.

This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.

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Source: http://www.labspaces.net/126467/Scientists_discover_how_epigenetic_information_could_be_inherited

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Multiple Sclerosis and a Second Wind - Multiple Sclerosis Blog

The last time I wrote a blog which included a musical reference I was on some pretty serious pain killers after my hip replacement and I got some serious (and quite deserved) flak from my sister for its sappiness. Well, we finally found the box with our music CDs in it today and it was nice to listen to a few tunes as we got on with our day?s work.

Billy Joel was on the playlist and his song ?You?re Only Human (Second Wind)? caught me up short.

I started thinking about a ?second wind? in relation to living with MS. In fact, an answer from a recent interview with Mike Jensen, a photographer living with multiple sclerosis, came to mind.

When I asked Mike about what he might have learned from living with MS his answer was spot on, ?This is a marathon,? he said, ?there are no touchdowns, and the game is never over. Don?t sweat the small stuff. Life in general, and MS in particular, is about learning to accommodate loss, hopefully with some grace and your dignity intact.?

Just like running a marathon, there are going to be times that we come up against ?the wall?, there are going to be times we feel like we can?t go on, there will be times that we just want to chuck in all in and sit on the sideline? then there is the second wind.

I don?t think an MS second wind is going to happen every day or every time I feel fatigued. In fact, I suspect that they only come on every few years and maybe only once or twice in an entire life with MS.

Maybe it?s at the point where we get our heads around multiple sclerosis and begin to try and wrap our hearts around our new life that we feel that burst of ?energy? (though we still might be very, very tired). I think of this renewal maybe more of spirit than of body and, let?s face it, our spirit can be dealt MS blows just as can our body.

So, I hope I haven?t sapped it up too much with this analogy (I?m sure Mangie will let me know if I did; what else are sisters for?) but I thought we could go into the weekend speaking of the concept. We know that many MS ?newbies? come to our pages seeking answers. Who better to give those answers than the thousands of you who live every day with MS and read our pages?

Wishing you and your family the best of health.

Cheers

Trevis

You can also follow me via our Life With MS Facebook page, on Twitter, and in our group on MS Connection.org. Also, check out our bi-monthly MS blog for the United Kingdom, look for our very special new monthly blog for the National MS Society, and don?t forget to check out TrevisLGleason.com.

Source: http://www.everydayhealth.com/blog/trevis-life-with-multiple-sclerosis-ms/multiple-sclerosis-and-a-second-wind/

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The Countdown, Episode 14 - Inflatable Space Station, Monkey Launch, Lunar Hedgehogs, Martian Groundwater, Saturn's Super-Sized Storm

[The text below is a modified transcript of this video.]

5) Inflatable Space Station

We?re this close to having a bouncy castle in space. NASA just ordered an inflatable module that will attach to the International Space Station.

Start up company Bigelow Aerospace won an 18 million dollar contract from NASA to build the Bigelow Expandable Activity Module, or BEAM. The module is just 4 meters long and 3.2 meters in diameter. That?s a little bit larger than your average car, but it?s designed to provide more living space for the ISS.

BEAM will travel to the space station in 2015, where it will be installed and inflated. For two years, the module will be monitored and tested to see how it holds up.

Then, BEAM will detach, fall towards Earth, and burn up. Because the walls of the inflatable module are about four times lighter than those currently used on the ISS, they?re much cheaper to lift into orbit. Their light weight could make blow-up modules the space technology of the future, whether used as free-floating space stations or for moon bases.

4) Monkey Launch

Last week, the Iranian space agency said it wants to launch a monkey into space?again. The first attempt, in the summer of 2011, failed. Officials gave no details about what went wrong.

According to the Iranians, within the next month a live Rhesus monkey will be launched into space aboard a Safir rocket. The monkey will reach a sub-orbit altitude and assuming everything goes to plan, return to Earth safely.

The Iranian government has said it wants send an astronaut into space by 2020 and to the moon by 2025. So, sending a monkey would be a significant first step. In the 1950s and 60s the US, French, and Russian governments tested the safety of their spacecraft by sending dogs, monkeys, and even chimps into space.

But critics of Iran?s space program are skeptical of such rocket tests and worry they are a just cover for developing long-range ballistic missiles capable of delivering a nuclear payload.

Politics aside, we hope the monkey makes it safely back to Earth.

3) Lunar Hedgehogs

Scientists must love sending bouncy objects into space. First it was an inflatable space station, then monkeys and now it?s spiky robots!

Researchers have proposed a mission to explore Phobos, one of the two moons circling Mars. Drafted by scientists from Stanford, NASA and MIT, the mission would have two stages. In the first, a surveyor satellite would travel to Phobos. And in the second, it would release spherical robots, called hedgehogs, onto the moon?s surface.

Because the gravity on Phobos is even weaker than on Mars, it would be difficult for a rover like Curiosity to get traction. But a spherical robot with spikes would be able to tumble, bounce and hop over the terrain. To create movement, the hedgehogs, about half a meter across, will have three rotating discs inside. This will enable them to fly in different directions and explore the surface.

While the surveyor monitors the orbit of Phobos from afar, the hedgehogs will study the chemical composition of the moon and analyze the soil and rocks.

If approved and funded, we?ll see the hedgehogs released in a decade.

2) Martian Groundwater

We already know water once flowed over the surface of Mars. Now pictures from the NASA Mars Reconnaissance Orbiter, suggest those waters may have run deep underground too.

Hi-res images of McLaughlin Crater show a pit 2.2 kilometers deep and 92 kilometers wide; slightly deeper and nearly three times wider than the Grand Canyon.

The pictures also reveal minerals, such as carbonate, that build up when water is present. But if a massive lake once filled the crater, where did the water come from? The Orbiter?s images show no evidence of surface streams leading to McLaughlin. So researchers suspect groundwater fed the lake instead.

This finding is particularly exciting because it suggests the Martian subsurface was once like Earth?s. And since microbes abound below our planet?s surface, life may have thrived underground on Mars as well.

The study is published in the January 20 online edition of Nature Geoscience (Scientific American is part of the Nature Publishing Group).

1) Saturn?s Super-Sized Storm

In December 2010, a giant thunderstorm broke out on Saturn. This wouldn?t normally be a big deal?similar storms form almost every Saturn-year, or once every 30 Earth years. But this storm was the longest ever recorded and it was huge.

Luckily, NASA?s Cassini spacecraft was nearby to observe as the storm spread across Saturn?s surface. In the lead was a lightning-filled section called the head, followed by a circulating vortex, and trailing, a tail of clouds. To imagine the scale of this enormous storm, you have to realize the vortex alone was about as wide as Earth. Plus, the weather disruptions caused an even bigger vortex to form higher in Saturn?s atmosphere. Although this one was four times larger than the original, it was only visible in the infrared range.

After a record 200 days, the monster storm finally dissipated in June 2011, and its description was published this month (preview). But the storm hasn?t quite finished. Saturn?s atmosphere will be feeling its aftermath for years to come.

- Portions of the script above written by Sophie Bushwick, Eric R. Olson & Isha Soni

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Source: http://rss.sciam.com/click.phdo?i=5c4b152912aa3145cd74e2f5f1ed42db

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Pentagon to remove ban on women in combat (Washington Post)

Share With Friends: | | Politics - Top Stories Stories, News Feeds and News via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/279209680?client_source=feed&format=rss

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New research may aid treatment of multiple myeloma patients

Jan. 23, 2013 ? A study led by Robert G. Hawley, Ph.D., professor and chair of the department of anatomy and regenerative biology at the George Washington University (GW) School of Medicine and Health Sciences (SMHS), may help predict which patients with multiple myeloma will respond better to certain treatments. The study, titled "Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1," was published in the American Journal of Hematology.

Multiple myeloma, the second most common blood cancer in the United States, is an incurable malignancy involving the white blood cells that normally produce antibodies. As the disease progresses, the multiple myeloma cells accumulate in the bone marrow, causing painful bone lesions and preventing normal blood cell production.

"Our hope is that the fluorescent assay we have developed will help physicians monitor the newest treatment option for multiple myeloma patients and determine how well it is working," said Hawley.

Hawley and his team of researchers reported a test that could be used to detect the multiple myeloma cells that survive chemotherapy and are responsible for disease relapse (referred to as tumor-propagating cells).

The researchers tested the hypothesis that the tumor-propagating cells in multiple myeloma exhibit stem cell-like properties that confer resistance to the chemotherapeutic agents used to treat the patients. The team's long-term goal is to characterize these so-called 'cancer stem cells' in order to develop new targeted therapies that will eradicate the cells and cure the disease. As a first step toward this goal, the research team used a new stem cell imaging dye CDy1, and they isolated pure populations of CDy1-bright and CDy1-dim cells from multiple myeloma cell lines by fluorescence-activated cell sorting (a specialized application of flow cytometry). These multiple myeloma populations were then characterized using RNA-seq 'deep-sequencing' gene expression analysis. Through this next-generation genomics approach, the researchers demonstrated that the CDy1-bright cells did indeed exhibit increased expression of many genes associated with stem cell activity. However, they also noted that the ABCB1 gene, which encodes the P-glycoprotein efflux transporter responsible for multi-drug resistance, was highly expressed in the CDy1-dim population. In functional studies, the investigators determined that dim CDy1 staining was due to the fact that the dye was being efficiently pumped out of the cells by the ABCB1 transporter.

Before the implementation of novel treatment regimens for multiple myeloma over the past decade, ABCB1-associated multi-drug resistance was routinely observed in patients who received conventional chemotherapy containing drugs that are ABCB1 substrates. With this in mind, Dr. Hawley and his colleagues examined new anticancer agents and discovered that high levels of ABCB1 conferred resistance to the second-in-class drug carfilzomib which is currently undergoing evaluation in multiple myeloma clinical trials. Moreover, increased resistance to carfilzomib in sensitive multiple myeloma cells following drug selection was associated with upregulation of ABCB1 cell-surface expression which correlated with increased transporter activity as measured by CDy1 efflux.

Of special note, carfilzomib (marketed under the brand name Kyprolis) recently received accelerated approval by the U.S. Food and Drug Administration for the treatment of multiple myeloma patients who have received at least 2 prior therapies and whose disease continues to worsen. Therefore, the next phase of the project, which is supported by a pilot research grant awarded in 2012 by The Dr. Cyrus and Myrtle Katzen Cancer Research Center at GW, will be to translate the laboratory findings to the clinic. This work, which will be carried out in collaboration with Imad Tabbara, M.D., professor of medicine at GW SMHS, will involve screening multiple myeloma patients to determine whether the CDy1 assay can help guide treatment decisions or predict which patients will respond better to carfilzomib.

"I first became interested in this subject as a graduate student at the Ontario Cancer Institute in the early 1980's," said Hawley. "However, I became disheartened as a principal investigator in the late 1990's when we were unable to cure the disease in a mouse model using cutting-edge cancer gene therapy, and I stopped working in this area. Despite recent therapeutic advances, multiple myeloma remains incurable. About a year and a half ago, I had a conversation with Robert Siegel, M.D., professor of medicine at GW SMHS and director of the Katzen Cancer Research Center, who encouraged me to enter the field again, and I am really happy that I did."

Hawley's team of researchers includes lead coauthors Teresa Hawley, B.S., director of the GW Flow Cytometry Core Facility, and Irene Riz, Ph.D., assistant research professor of anatomy and regenerative biology, along with Louis DePalma, M.D., professor of pathology and of anatomy and regenerative biology, and Weiqun Peng, Ph.D., associate professor of physics and of anatomy and regenerative biology, together with collaborators Jun Zhu, Ph.D., director of the DNA Sequencing and Computational Biology Core at the National Heart, Lung and Blood Institute of the National Institutes of Health, and Young-Tae Chang, Ph.D., head of the Laboratory of Bioimaging Probe Development at the National University of Singapore Agency for Science, Technology and Research.

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The above story is reprinted from materials provided by George Washington University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Teresa S. Hawley, Irene Riz, Wenjing Yang, Yoshiyuki Wakabayashi, Louis DePalma, Young-Tae Chang, Weiqun Peng, Jun Zhu, Robert G. Hawley. Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1. American Journal of Hematology, 2013; DOI: 10.1002/ajh.23387

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/rtJCxVuNovQ/130123133327.htm

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