Friday, May 31, 2013

This Is the Propane Tank Bench of Hank Hill's Dreams

This Is the Propane Tank Bench of Hank Hill's Dreams

The King of the Hill definitely never went this far with his love for an open flame. Meet Colin Selig, a California designer who fabricates sleek, sinuous couches out of metal sheets cut from empty propane tanks.

Selig's inspiration for one of his many pieces of upcycled petro-furniture came not from a King of the Hill marathon, but from a gentle suggestion from his wife that he clean the house. The very first chair started with an old propane tank they had on their property that Selig didn't want to get rid of. Here's what he has to say about the sustainable seats:

I was intrigued by the design challenge and ecological statement involved in taking this ubiquitous, utilitarian container out of the waste stream and transforming it into an object more sensual in form and sophisticated in function. After making sure the tank was purged of any remaining gas I began by cutting off the ends and mounting them on my work table. Then I welded in a seat and back rest from the central cylindrical portion.

The end-products are inspired pieces of furniture that look like they belong in Tomorrowland. They're eye-catching, but are they comfortable? Yup, says Selig, thanks to the old tank's friendly curves. This one is based on Salvador Dal?'s "Mae West" sofa:

This Is the Propane Tank Bench of Hank Hill's Dreams

And here a few other designs:

This Is the Propane Tank Bench of Hank Hill's Dreams

This Is the Propane Tank Bench of Hank Hill's Dreams

This Is the Propane Tank Bench of Hank Hill's Dreams

Using a plasma cutter to cut the tanks into careful pieces, Selig's made about 30 benches since the project started in 2010. And damnit Bobby, they appeal to the luxury crowd, retailing at places like Neiman Marcus and the Internnational Contemporary Furniture Fair for anywhere between $4,000-$11,000, depending on the size. Who knew this is where propane tanks go to die? Or rather, to begin a new life! [Colin Selig via AtlanticCities]

Image credit: Colin Selig

Source: http://gizmodo.com/this-is-the-propane-tank-bench-of-hank-hills-dreams-510650109

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Interleukin-22 protects against post-influenza bacterial superinfection

May 30, 2013 ? Researchers from the Pasteur Institute, Lille, France have shown in a mouse model that interleukin-22 protects against bacterial superinfections that can arise following influenza. Their research is published in the June 2013 issue of the Journal of Virology.

Influenza A viral infection can lead to primary pneumonia and, later on, to serious complications including secondary bacterial pneumonia and sepsis. Post-influenza bacterial superinfections that occur during seasonal epidemics and pandemics are of great concern to human health and impose a considerable socio-economic burden.

"It is therefore critical that we reach a better understanding of the causes of and potential treatments for post-influenza bacterial superinfection," says corresponding author Fran?ois Trottein.

"Mouse studies have revealed that impairment of the host innate immune defense, as well as lung damage caused by the virus are cardinal features of bacterial superinfection," says Trottein. The authors tested the hypothesis that interleukin-22, an important cytokine implicated in mucosal immunity, inflammation and tissue repair, might play an important role during influenza.

The authors show that several cell types belonging to the innate immune system produce interleukin-22 soon after infection. They also demonstrate that the lack of interleukin-22 aggravates the pathogenesis that develops in the lungs and in particular exacerbates epithelial damage caused by the virus. Furthermore, endogenous interleukin-22 displays a protective role during secondary bacterial (pneumococcus) infection in the mouse system.

Although the mechanisms sustaining the protective effect of interleukin-22 are not yet fully elucidated, the authors speculate that its beneficial effect is due to its role in the maintenance of epithelial integrity.

"If it works as well in humans, the production of interleukin-22 could confer a substantial benefit on patients having flu," says Trottein.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/uGjq-g9Gn74/130530111303.htm

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Engadget Mobile Podcast 180 - 05.29.13

Engadget Mobile Podcast 179 - 05.09.13

It's been three long weeks since you last heard us, but the news cycle has been far from quiet -- we hope you'll forgive our absence. In this episode we'll focus on Google I/O and catch up on the latest in mobile from BBM to HTC. To apologize for being away, we're also including an awesome downloadable ringtone for the noise of horror Brad makes whenever the word phablet is muttered. Get to streaming below and subscribe after the break.

Hosts: Myriam Joire (tnkgrl), Brad Molen

Producer: Joe Pollicino

Music: Tycho - Coastal Brake (Ghostly International)

Hear the podcast

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Source: http://www.engadget.com/2013/05/29/engadget-mobile-podcast-180-05-29-13/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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Thursday, May 30, 2013

Wrestling, 7 other sports take case to IOC ? Artesia News

Sorry, Readability was unable to parse this page for content.

Source: http://www.artesianews.com/2013/05/29/ap-news/sports-ap-news/wrestling-7-other-sports-take-case-to-ioc-2/

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internet marketing consulting | eCommerce Investments Europe

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As experienced professionals in eCommerce we launched this company?to bring the skills necessary to develop online businesses?of entrepreneurs?with the maximum effectiveness.

Our goal from the beginning has been to help entrepreneurs to create their business on Internet, fast and error-free ,?making us the partner on the internet,?and collaborating from the start in a very clear way

As eCommerce Consultants and eCommerce Investors,?We have created two programs in?order to adapt to the maximum amount of possible?projects.

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With our eCommerce Consulting Program, We fully developed and drive Internet Projects?to get the full potential of the online business, and we do this?covering all development costs and managing all processes on the Internet, and when the project start to?generate business?we will receive a percentage of sales?during the agreed time to recover our investment?and of course also to earn money

To seal each alliance?we need a initial security payment?and also a minimum period of collaboration, thats all!

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Internet Investors over small and medium eCommerce projects with solid business and growth process,

We provide our expertise , small business finance?and we involve ourselves in the online business development, becoming in your technology partner in your eCommerce companies, to?take over the development cost, and technical management of online businesses, in exchange for a share of the company and online sales percentage

Developing an online business requires many skill-sets, not just technical, also marketing, graphics, positioning, social media, Internet marketing service.. and all the skills combined and contributed by the right people to mold the successful online venture

A eCommerce Project should be handle only for one eCommerce agency which handles all processes for the Internet Business Creation, this is crucial?to go the way of success, because on this way will take advantage of all the synergies,?avoiding double spending on items to be overlapped in the Internet business creation process

Each of us in eCommerce Investments have had our share of success and failure, and our experiences on both sides is what makes us online business experts.?we have created our own business,?and participated in many others during the last years.?so we know what to do?and when to do it,?to set up an internet business .

We exist to facilitate the online business development knowledge that most small or medium sized eCommerce projects becoming in the Internet Partner to the Companies and entreperneurs who want to?create your online business?in a solid, sustainable and long-term way

Now if you fit with our work philosophy and want to Create, expand or boost your internet business in partnership with us, using our?internet marketing consulting,?let us know you want to collaborate.

Source: http://ecommerce-investments.com/internet-marketing-consulting/?utm_source=rss&utm_medium=rss&utm_campaign=internet-marketing-consulting

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Wednesday, May 29, 2013

Ding dong! Michele Bachmann?s retiring (Americablog)

Share With Friends: Share on FacebookTweet ThisPost to Google-BuzzSend on GmailPost to Linked-InSubscribe to This Feed | Rss To Twitter | Politics - Top Stories Stories, News Feeds and News via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/309129865?client_source=feed&format=rss

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Leaked Windows 8.1 build points to the Start button's return

Leaked Windows 81 shots point show Start button, wallpaper on home screen

When we last got a peek at Windows 8.1 "Blue," most of the updates lurked under the surface: rumors of a Start button revival didn't pan out. Flash forward to Paul Thurrott's screenshots of a newer build, however, and it's a different story. The leaked code has the Start button once more occupying a spot on the desktop taskbar, with behavior reportedly like what we've seen with Stardock's Start 8 utility. More throwbacks also appear to be in store. Users can now transfer their desktop wallpaper to the Start screen, and the storied boot-to-desktop option is available -- if turned off by default. Microsoft hasn't acknowledged the existence of these (or any) Windows 8.1 features, but the rapidly approaching Build conference suggests that we'll learn more in the near future.

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Via: The Verge

Source: SuperSite for Windows

Source: http://www.engadget.com/2013/05/29/leaked-windows-8-1-build-points-to-the-start-button-return/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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RailHawks set to host Galaxy, Rogers

RailHawks set to host Galaxy, Rogers

Published: 2013-05-28 12:45:00
Updated: 2013-05-28 15:57:14

Updated at 3:57 p.m.

The Carolina RailHawks will host the two-time defending MLS Champion, LA Galaxy, in the third round of the 2013 Lamar Hunt U.S. Open Cup on Wednesday night at 7:00 pm at WakeMed Soccer Park.

This will be the second consecutive year that the two teams have met in the third round of the U.S. Open Cup. In 2012, the RailHawks beat the Galaxy, 2-1, in front of a sold-out crowd in Cary, NC.

?We will have another great turnout for another high level soccer match in the Triangle," the team said in a statement. "Tickets have been purchased from over 107 different cities and 15 different states. VIP and Club sections have sold out, but good seats are still available in Premium and Spectator seating categories.?

Robbie Rogers, the first openly gay soccer player, will play in Wednesday?s game, which will broadcasted on wralsportsfan.com and WRAL-2.

Individual tickets are still available for Wednesday night's match.
?

Copyright 2013 by Capitol Broadcasting Company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Source: http://www.wralsportsfan.com/railhawks-set-to-host-galaxy-rogers-/12490887/

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Google Maps brings biking navigation to six European countries

Google Maps brings biking navigation to six European countries

Summer is the prime season for European cyclists, whether they're racing the Tour de France or just embarking on voyages of self-discovery. It's a good thing, then, that Google Maps' biking directions have reached six more European countries. Those in France, Ireland, Germany, Liechtenstein, Luxembourg and Poland can now plot pedal-friendly routes using their phones and the web. Google may miss a hidden trail or two when it's crowdsourcing the data through Map Maker, but the upgrade should still help riders avoid the inevitable crush of tourist traffic.

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Source: Google Europe Blog

Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/-0_WVMyFzBU/

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Twitter for iOS and Android updated with tweet preview, easier photo sharing

Twitter for iOS updated with tweet preview and expanded timelines

There doesn't seem to be much broken that needs fixing on Twitter for iOS or Android, for that matter. Which is why the latest update to hit the App Store and Google Play deals mostly in minor UI tweaks. Now, Twitaholics that bump up the Twitter app on both mobile platforms will enjoy a cleaner compose look that lets users preview outgoing tweets (including full sized photos), tag locations and quickly share photos from their gallery. On the iOS end, notifications have been added for when your friends newly sign-up for the service, as well as an expanded timeline view that does away with borders. While Android users now have access to more detailed information from the notification tray. Naturally, there are the requisite, unspecified bug fixes bundled into the software bump, but that bit's unglamorous and (thankfully) left devoid of detail. That's right, it's nothing to get hot and bothered over folks -- just a minor facelift to further enable your oversharing.

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Source: iTunes, Google Play, Twitter

Source: http://www.engadget.com/2013/05/29/twitter-for-ios-updated-with-tweet-preview-and-expanded-timeline/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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Tuesday, May 28, 2013

AP Sources: Bobcats hire Clifford as coach

CHARLOTTE, N.C. (AP) ? The Charlotte Bobcats have hired Los Angeles Lakers assistant Steve Clifford to become their new coach.

Two people familiar with the situation said Monday that Clifford had agreed to a three-year contact. They spoke to The Associated Press on condition of anonymity because the announcement has not been made public.

Clifford replaces Mike Dunlap, who was fired after going 21-61 in his only season as coach.

Clifford has worked as an assistant in New York, Houston, Orlando and Los Angeles, but has never been a head coach at the NBA level. He has worked under both Jeff and Stan Van Gundy.

He becomes the sixth coach of the Bobcats since 2006-07.

The Bobcats made the move to hire Clifford on Monday, one day before he was slated for a second interview with the Milwaukee Bucks for their coaching vacancy.

Clifford came to Los Angeles with Dwight Howard from the Magic and was retained for the 2013-14 season as an assistant coach. However, the Lakers granted him permission to interview with other teams.

Prior to joining the Lakers, Clifford spent five seasons with Orlando, working alongside Stan Van Gundy. During that five-year span, the Magic were 259-135 (.657) and reached the NBA Finals in 2009.

Clifford also spent four seasons as an assistant with the Rockets under Jeff Van Gundy and three with the Knicks.

Jeff Van Gundy, now an NBA broadcaster, said he's known Clifford since they coached together at the Jim Boeheim camp in 1985 in Syracuse, N.Y., and called him "a person with impeccable integrity."

He also thinks he's going to be a pretty good NBA head coach because of the relationships he builds with players and fellow coaches.

"He's a brilliant basketball coach who relates to all kinds of people well and I think he will do an absolutely fantastic job with the talent at hand," Jeff Van Gundy said. "I'm so happy for one of the good guys in the league to get this opportunity."

Clifford has worked in North Carolina briefly before as an assistant coach for one year at East Carolina.

The Bobcats fired Dunlap in April after just one season.

Dunlap struggled with the transition from the college game to the NBA and game management. He often butted heads with his veteran players, which is likely one of the reasons the Bobcats decided to go after an experienced NBA assistant like Clifford.

Bobcats president of basketball operations Rod Higgins said in mid-April he and general manager Rich Cho met with the players and Dunlap before approaching owner Michael Jordan and asking him to make a coaching change.

"The change was allowed," Higgins said in April.

Higgins said at the time player input was "a part of the process, but not the only indicator."

Higgins was asked in April what he wanted in a new coach.

"We want to hire a great leader, (and) the player development aspect is still vitally important to us because of our youth," Higgins said. "Obviously you want a fantastic X-and-O coach. Someone who can make our players better, and help us win games."

The Bobcats seemed to place an emphasis on finding a defensive-minded coach after finishing near the bottom of the league in most defensive categories last season.

Along with the Clifford, the Bobcats interviewed at least five other known candidates for the position.

They spoke early on in the process to former Los Angeles Clippers and Phoenix Suns coach Alvin Gentry, Suns assistant Elston Turner, Cleveland Cavaliers assistant Nate Tibbetts and Houston Rockets assistant Kelvin Sampson.

The Bobcats again considered former Lakers assistant Quin Snyder, now a head coach of a professional team in Russia. Snyder and Jerry Sloan were among the three finalists for the job last year that was given to Dunlap.

Source: http://news.yahoo.com/ap-sources-bobcats-hire-clifford-coach-233954486.html

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Monday, May 27, 2013

PFT:?Jay-Z's recruitment of Smith under scrutiny

JayZGetty Images

Publicly, the NFLPA has been mum on the manner in which the sports agency owned by Jay-Z recruited Jets quarterback Geno Smith.? Privately, the NFLPA will say just enough to spark action.

According to Albert Breer of NFL Network, the union plans to send a letter to agent Kim Miale, the certified agent who works for Jay-Z?s Roc Nation and who represents Smith.? The NFLPA wants to know whether and to what extent Jay-Z was involved in recruiting Smith to hire Miale.

Under a rule passed by the NFLPA in 2012, only NFLPA-certified agents may be involved in recruiting clients.? Thus, if Jay-Z engaged in any recruitment of Smith to hire Miale, Miale has a problem.

Complicating matters are comments from Smith?s advisor, John Thornton, to CBS and a photo of Jay-Z and a photo that appeared in social media of Smith with Jay-Z, before Smith hired Miale.

Said Thornton, who later claimed that he was misquoted:? ?It really all came down to who he was most comfortable with.? I was in those meetings and Jay-Z connected with him on many levels.?

In our view, information sought by the NFLPA could include the full list of Roc Nation employees who met with or talked to Smith, the circumstances and timeline surrounding Miale?s arrival at Roc Nation, whether Smith actually met Miale at any point before signing the Standard Representation Agreement, the number of times Smith and Miale communicated during the recruitment process, the number of times Miale communicated with Thornton and other Smith advisors, the number of times Smith and Jay-Z met and communicated during the recruitment process, and the number of times Jay-Z communicated with Thornton and other Smith advisors.

Phone records, emails, and other documents could be sought to confirm the things that potential witnesses may say, given the strong incentive to conceal any evidence of recruiting by Jay-Z.? Interviews could be conducted of Smith, Miale, Thornton, Jay-Z, and others with knowledge of the situation.

The biggest problem for the NFLPA could come from its lack of jurisdiction over Jay-Z.? While the union can take action against Miale, the NFLPA can do nothing to Jay-Z or anyone else who doesn?t fall under the union?s regulatory umbrella.? Indeed, the NFLPA lacks the power to compel Jay-Z or anyone else not certified by the NFLPA to cooperate.

Thus, the problem could repeat itself, with the NFLPA suspending Miale and Jay-Z then hiring another certified agent.? And so on.? While we?re not advocating this specific solution, the only way the NFLPA could end the cycle (if Jay-Z intends to be involved in recruiting clients and if he can?t or won?t obtain NFLPA certification) would be to issue a blanket statement that any agent who associates with Jay-Z automatically would be subject to discipline.

The union is a long way from that point.? But the decision to look into the Miale-Smith arrangement represents much more than some agents thought the NFLPA would do.? Those agents and plenty of others will be keenly interested in how the inquiry proceeds, the information it uncovers, and the manner in which the situation is resolved.

Source: http://profootballtalk.nbcsports.com/2013/05/25/nflpa-examining-roc-nations-recruitment-of-geno-smith/related/

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Heat break out in Game 3 for 2-1 lead over Pacers

Miami Heat's Udonis Haslem (40) celebrates with Chris Bosh (1) after Haslem made a shot and was fouled during the first half of Game 3 of the NBA Eastern Conference basketball finals against the Indiana Pacers in Indianapolis, Sunday, May 26, 2013. (AP Photo/Nam H. Huh)

Miami Heat's Udonis Haslem (40) celebrates with Chris Bosh (1) after Haslem made a shot and was fouled during the first half of Game 3 of the NBA Eastern Conference basketball finals against the Indiana Pacers in Indianapolis, Sunday, May 26, 2013. (AP Photo/Nam H. Huh)

Indiana Pacers players, from left, Lance Stephenson, D.J. Augustin, Ian Mahinmi, Paul George, Sam Young and George Hill watch late in Game 3 of the NBA Eastern Conference basketball finals against the Miami Heat in Indianapolis, Sunday, May 26, 2013. The Heat won 114-96. (AP Photo/Michael Conroy)

Miami Heat's Chris Andersen, left, grabs a rebound from Indiana Pacers' Tyler Hansbrough during the second half of Game 3 of the NBA Eastern Conference basketball finals in Indianapolis, Sunday, May 26, 2013. (AP Photo/Michael Conroy)

Miami Heat forward LeBron James, right, greets guards Ray Allen and Dwyane Wade (3) during the first half against the Indiana Pacers of Game 3 in their Eastern Conference Finals NBA basketball series in Indianapolis, on Sunday, May 26, 2013. (AP Photo/The Miami Herald, Al Diaz) MAGS OUT

Miami Heat's Dwyane Wade (3) goes makes a pass against Indiana Pacers' Roy Hibbert (55) and Paul George during the second half of Game 3 of the NBA Eastern Conference basketball finals in Indianapolis, Sunday, May 26, 2013. (AP Photo/Michael Conroy)

(AP) ? The Indiana Pacers didn't see this version of Udonis Haslem coming. There was no reason to.

Haslem, a veteran forward who had scored in single digits in six of his previous seven playoff games, finished with 17 points on 8-for-9 shooting to help the Miami Heat beat the Pacers 114-96 in Game 3 of the Eastern Conference finals on Sunday night.

The Heat took a 2-1 lead in the series and regained homecourt advantage with Game 4 set for Tuesday night in Indianapolis.

Haslem went a quiet 1-for-7 from the floor in the first two games of the series, but he looked for his shot early and often in Game 3. His mid-range jumpers constantly left 7-foot-2 center Roy Hibbert out of position. Hibbert had been playing slightly loose defense on Haslem and Chris Bosh to help protect the rim and the lane against LeBron James and Dwyane Wade.

Hibbert said Haslem's effectiveness forced him to change his approach.

"I think he was really the guy that pushed them, the catalyst for them," he said. "Just him hitting those shots really made us have to think on defense. Who do we guard? Do we guard the paint, or do we have to go out to the shooters out in the corner."

Pacers coach Frank Vogel was heavily criticized for taking Hibbert out of Game 1 before James' game-winning layup. Vogel said he made the move because he was worried Bosh would get open for an easy jumper. The Heat spent 48 minutes showing Pacers fans why Vogel's Game 1 decision might not have been such a bad idea.

"That's what Miami does, they space you out," he said. "They make it difficult to have a rim protector in the game at all times. They challenge you to keep a guy at the rim and still make them close out to an 18-foot jump shooter. We have to account for that."

While Haslem and Bosh pulled Hibbert and power forward David West away from the basket, James took over as the Heat's post presence, overpowering and dominating All-Star forward Paul George.

"I made a conscious effort to get down in the post tonight, to put pressure on their defense," James said. "The coaching staff wanted me to be down there tonight, and my teammates allowed me to do that."

James, bouncing back after two late turnovers cost Miami in Game 2, had 22 points, four rebounds and three assists. Hours after Wade learned he would only be tagged with a flagrant foul from Game 2 and not a suspension, he finished with 18 points, eight assists and four rebounds. Bosh added 15 points and three rebounds, and all five Miami starters reached double figures.

Miami outscored Indiana 56-32 in the paint, but perhaps that much should be expected from a team with this much scoring punch ? one that has won 23 of its last 24 games on the road.

The other stuff, not so much.

Miami committed a playoff franchise-low one turnover in the first half and finished with only five. James finished with none.

The Heat shot 54.5 percent against a Pacers team that finished the regular season with the NBA's best defensive field goal percentage and also made 24 of 28 free throws. They matched the highest scoring output in a quarter during this season's playoffs with 34, broke the franchise playoff record for points in a half (70) and fell one point short of tying the third-highest point total in a playoff game in franchise history.

But the biggest difference between the first two games and Sunday night's rout was James' work on the inside.

"It was something we wanted to get just to help settle us and get into a more aggressive attack," Heat coach Erik Spoelstra said of the decision to post up the 6-foot-8 James. "We wanted to be a little more aggressive, a little more committed to getting into the paint and seeing what would happen. LeBron was very committed and focused not to settle."

Now it's the Pacers turn to adjust.

West led Indiana with 21 points and 10 rebounds, while Hibbert had 20 points and 17 boards. George finished with 13 points and eight assists, not nearly enough for the Pacers to remain perfect at home in the postseason.

Miami took advantage of a wild first quarter to build a 34-30 lead, then turned the game with James taking control in a 12-point second quarter. He scored half of the points in an 8-2 run that gave the Heat what was then their biggest lead of the series, 42-32.

A few minutes later, James did it again, making a 15-footer with 1.3 seconds left in the half to give Miami a 70-56 lead at the break ? and the franchise record.

Indiana opened the second half looking more like the team that had given Miami fits in Games 1 and 2. The Pacers hit back-to-back 3-pointers and got a three-point play from George Hill. When Lance Stephenson followed that with 1 of 2 free throws, the lead had been cut to 74-67.

It didn't last.

Miami countered with a 9-4 run, extended the lead to 91-76 after three and made it 99-78 early in the fourth. Indiana never challenged again ? the 18-point margin matching Indiana's worst home loss of the season ? even though James scored only four second-half points.

"If you're not perfect guarding them, they'll do what they did to us tonight," Vogel said. "Sometimes when you are perfect with your coverages, they still find a way to make baskets. But we didn't have a great defensive night."

NOTES: Miami's best scoring half before Sunday was a 68-point effort against Chicago on April 24, 2006. ... Miami's Chris Andersen has made 16 consecutive shots in the playoffs. ... Indiana University basketball coach Tom Crean, former vice presidential candidate Sarah Palin and San Francisco 49ers coach Jim Harbaugh attended the game. Harbaugh drove the pace car at the Indy 500. ... The victory was Miami's first at Indiana this season after dropping both regular-season meetings in Indy.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/347875155d53465d95cec892aeb06419/Article_2013-05-27-BKN-Heat-Pacers-Folo/id-030c228a744c491d9e67fc9ecdb93de2

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US intelligence embraces debate in security issues

WASHINGTON (AP) ? In the months leading up to the killing of Osama bin Laden, veteran intelligence analyst Robert Cardillo was given the nickname "Debbie Downer." With each new tidbit of information that tracked bin Laden to a high-walled compound in northern Pakistan ? phone records, satellite imaging, clues from other suspects ? Cardillo cast doubt that the terror network leader and mastermind was actually there.

As the world now knows well, President Barack Obama ultimately decided to launch a May 2011 raid on the Abbottabad compound that killed bin Laden. But the level of widespread skepticism that Cardillo shared with other top-level officials ? which nearly scuttled the raid ? reflected a sea change within the U.S. spy community, one that embraces debate to avoid "slam-dunk" intelligence in tough national security decisions.

The same sort of high-stakes dissent was on public display recently as intelligence officials grappled with conflicting opinions about threats in North Korea and Syria. And it is a vital part of ongoing discussions over whether to send deadly drone strikes against terror suspects abroad ? including U.S. citizens.

The three cases provide a rare look inside the secretive 16 intelligence agencies as they try to piece together security threats from bits of vague information from around the world. But they also raise concerns about whether officials who make decisions based on their assessments can get clear guidance from a divided intelligence community.

At the helm of what he calls a healthy discord is Director of National Intelligence James Clapper, who has spent more than two-thirds of his 72 years collecting, analyzing and reviewing spy data from war zones and rogue nations. Clapper, the nation's fourth top intelligence chief, says disputes are uncommon but absolutely necessary to get as much input as possible in far-flung places where it's hard for the U.S. to extract ? or fully understand ? ground-level realities.

"What's bad about dissension? Is it a good thing to have uniformity of view where everyone agrees all the time? I don't think so," Clapper told The Associated Press in an interview Friday. "...People lust for uniform clairvoyance. We're not going to do that."

"We are never dealing with a perfect set of facts," Clapper said. "You know the old saw about the difference between mysteries and secrets? Of course, we're held equally responsible for divining both. And so those imponderables like that just have to be factored."

Looking in from the outside, the dissension can seem awkward, if not uneasy ? especially when the risks are so high.

At a congressional hearing last month, Rep. Doug Lamborn, R-Colo., read from a Defense Intelligence Agency report suggesting North Korea is able to arm long-range missiles with nuclear warheads. The April 11 disclosure, which had been mistakenly declassified, came at the height of Kim Jong Un's sabre-rattling rhetoric and raised fears that U.S. territory or Asian nations could be targeted for an attack.

Within hours, Clapper announced that the DIA report did not reflect the opinions of the rest of the intelligence community, and that North Korea was not yet fully capable of launching a nuclear-armed missile.

Two weeks later, the White House announced that U.S. intelligence concluded that Syrian President Bashar Assad has probably used deadly chemical weapons at least twice in his country's fierce civil war. But White House officials said the intelligence wasn't strong enough to justify sending significant U.S. military support to Syrian rebels who are fighting Assad's regime.

Because the U.S. has few sources to provide first-hand information in Syria, the intelligence agencies split on how confident they were that Assad had deployed chemical weapons. The best they could do was conclude that the Syrian regime, at least, probably had undertaken such an effort. This put Obama in the awkward political position of having said the use of chemical weapons would cross a "red line" and have "enormous consequences," but not moving on the news of chemical weapons use, when the occasion arose, because the intelligence was murky.

Lamborn said he welcomes an internal intelligence community debate but is concerned that the North Korean threat was cavalierly brushed aside.

"If they want to argue among themselves, that's fine," said Lamborn, a member of the House Armed Services Committee. However, he also said, "We should be cautious when evaluating different opinions, and certainly give credence to the more sobering possibilities. ... When it comes to national security, I don't think we want to have rose-colored glasses on, and sweep threats under the rug."

Clapper said that, in fact, U.S. intelligence officials today are more accustomed to predicting gloom and doom. "We rain on parades a lot," he said.

Current and former U.S. intelligence officials say the vigorous internal debate was spawn from a single mistake about a threat ? and an overly aggressive response.

Congress demanded widespread intelligence reform after the Sept. 11, 2001, terror attacks, to fix a system where agencies hoarded threat information instead of routinely sharing it. Turf wars between the CIA and the FBI, in particular, were common. The CIA generally was considered the nation's top intelligence agency, and its director was the president's principal intelligence adviser.

The system was still in place in 2002, when the White House was weighing whether to invade Iraq. Intelligence officials widely ? and wrongly ? believed that then-dictator Saddam Hussein possessed weapons of mass destruction. By December 2002, the White House had decided to invade and was trying to outline its reasoning for doing so when then-CIA Director George Tenet described it as "a slam-dunk case."

The consequences were disastrous. There were no WMDs, but the U.S. wound up in a nearly nine-year war that killed nearly 5,000 American soldiers, left more than 117,000 Iraqis dead, and cost taxpayers at least $767 billion. The war also damaged U.S. credibility throughout the Mideast and, to a lesser extent, the world. Tenet later described his "slam-dunk" comment as "the two dumbest words I ever said."

Two years later, Congress signed sweeping reforms requiring intelligence officials to make clear when the spy agencies don't agree. Retired Amb. John Negroponte, who became the first U.S. national intelligence director in 2005, said if it hadn't been for the faulty WMD assessment "we wouldn't have had intelligence reform."

"It was then, and only then that the real fire was lit under the movement for reform," Negroponte said in a recent interview. "In some respects it was understandable, because Saddam had had all these things before, but we just allowed ourselves to fall into this erroneous judgment."

To prevent that from happening again, senior intelligence officials now encourage each of the spy agencies to debate information, and if they don't agree, to object to their peers' conclusions. Intelligence assessments spell out the view of the majority of the agencies, and highlight any opposing opinions in a process similar to a Supreme Court ruling with a majority and minority opinion.

The result, officials say, is an intelligence community that makes assessments by majority vote instead of group-think, and where each agency is supposed to have an equal voice. In effect, officials say, the CIA has had to lean back over the last decade as officials have given greater credence to formerly marginalized agencies. Among them is the State Department's Bureau of Intelligence and Research, which warned before the 2003 Iraq invasion that the CIA had overestimated Saddam's prospects to develop nuclear weapons.

Also included is the DIA, which has increased its ability during the Iraq and Afghanistan wars to gather ground-level intelligence throughout much of the Mideast and southwest Asia. In an interview, DIA director Lt. Gen. Michael Flynn would not discuss his agency's debated assessment on North Korea, but described a typical intelligence community discussion about "ballistic missiles in name-that-country" during which officials weigh in on how confident they feel about the information they're seeing.

"In the intelligence community we should encourage, what I would call, good competition," Flynn said. He added: "The DIA, in general, is always going to be a little bit more aggressive. ...As a defense community, we're closer to the war-fighting commanders; it may be in that part of our DNA."

Without the all the varying strands of information pieced together from across the intelligence agencies, officials now say the bin Laden raid would not have happened.

The CIA was running the manhunt, but the National Security Agency was contributing phone numbers and details from conversations it had intercepted in overseas wiretaps. The National Geospatial Agency provided satellite imagery of the Abbottabad compound ? from years past and more recently ? to get a sense of who might be living there. And it produced photos for a tall man walking the ground inside the compound ? even though they were never able to get a close look at his face.

One of the compound's balconies was blocked off by a seven-foot wall, Cardillo said, raising questions about who might want his view obscured by such a tall barrier. Officials also were keeping tabs on the people who lived in the compound, and trying to track how often they went outside.

Cardillo was vocal about his skepticism in each strand of new information he analyzed during the eight months he worked on the case, prompting colleagues to rib him about being a "Debbie Downer."

"I wasn't trying to be negative for the sake of being negative," Cardillo, a deputy national intelligence director who regularly briefs Obama, said in an interview Friday. "I felt, 'Boy, we've got to press hard against each piece of evidence.' Because, let's face it, we wanted bin Laden to be there. And you can get into group-think pretty quick."

To prevent that from happening, officials encouraged wide debate. At one point, they brought in a new four-man team of analysts who had not been briefed on the case to independently determine whether the intelligence gathered was strong enough to indicate bin Laden was there.

Their assessment was even more skeptical than Cardillo's. In the end the call to launch the raid was so close that, as officials have since said, it might as well have come down to a flip of a coin.

In most intelligence cases, the decisions aren't nearly as dramatic. But the stakes are always high.

Over the last four years, the Obama administration has expanded the deadly U.S. drone program in its hunt for extremists in terror havens. The drones have killed thousands of people since 2003 ? both suspected terrorists and civilian bystanders ? among them four U.S. citizens in Pakistan and Yemen.

The Justice Department this week said only one of the four Americans, Anwar al-Awlaki, who officials believe had ties to at least three attacks planned or carried out on U.S. soil, was targeted in the strikes. The other three were collateral damage in strikes aimed at others.

Though policy officials make the final call on when to strike, the intelligence community builds the case. Analysts must follow specific criteria in drone assessments, including near certainty of the target's whereabouts and the notion that bystanders will not be killed. They must also look at the likelihood of whether the terror suspects can be captured instead of killed.

In these sorts of life-and-death cases, robust debate is especially necessary, Clapper said. And if widespread doubts persist, the strike will be canceled.

"It is a high bar, by the way, and it should be," Clapper said. "If there is doubt and argument and debate ? and there always will be as we look at the totality the information we have on a potential target ? we damn well better have those debates and resolve those kinds of issues among ourselves the best we can."

Few have been more skeptical of the decision-making behind the drone strikes than Sen. Ron Wyden, an Oregon Democrat who has sat on the Senate Intelligence Committee since 2001. Earlier this year, he threatened to block Senate confirmation of CIA Director John Brennan until the White House gave Congress classified documents outlining its legal justification for targeting American citizens in drone strikes. The documents were turned over within hours of Brennan's confirmation hearing.

Generally, Wyden says, spy assessments have become far more reliable over the last decade, and especially since the flawed Iraq intelligence. But he maintains Congress should be given greater access to classified documents to independently verify intelligence analysis and assessments ? and safeguard against being misled.

"Certainly, solid analysis from the intelligence community is one of the most important sources of information that I have," Wyden said in an interview this month. "And if you look back, and the analysis is incorrect or if it's written in a way that portrays guesses at certainties, that can contribute to flawed decision-making.

"That's why I felt so strongly about insisting on actually getting those documents with respect to drones," Wyden said. "I've got to be able to verify it."

Clapper, who has been working on intelligence issues for a half-century, is well aware of how jittery many Americans feel about the spy community. The internal debates, he believes, should bolster their confidence that intelligence officials have thoroughly weighed all aspects of some of the world's most difficult security issues before deciding how high a threat they pose.

"I think it'd be very unhealthy ? and I get a lot of pushback from people ? if I tried to insist that you will have one uniform view and this is what I think, and that's what goes. That just wouldn't work," he said. "There is the fundamental tenet of truth to power, presenting inconvenient truths at inconvenient times. That's part of our system."

___

Follow Lara Jakes on Twitter at https://twitter.com/larajakesAP

Source: http://news.yahoo.com/us-intelligence-embraces-debate-security-issues-122715492.html

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Seen and heard in Cannes

CANNES, France (AP) ? Associated Press journalists open their notebooks at the 2013 Cannes Film Festival

UNCOMFORTABLE MOMENTS FOR ACTRESS AS DAD WATCH LOVE SCENES:

Talk about awkward.

Not only did Adele Exarchopoulos' father watch the graphic sex scenes between her and another woman in the movie "Blue Is The Warmest Color (La Vie D'Adele)," in competition at the Cannes Film Festival, she was with him when he took in the film at its premier.

"During the love scenes I was ill at ease with my father being there, but at the same time I wanted him to be there. And I knew that he would probably have a very good reaction because it's all a question of intelligence and he's intelligent and therefore would understand," said Exarchopoulos.

She added:

"During the sex scene I was looking at him, like, 'Oh my god, how does he feel' because I don't want to make him uncomfortable, you know?" the 19-year-old said in an interview. "I think I was trying to take a certain distance from what was happening during the love scenes."

In the film, Exarchopoulos stars as 15-year-old Adele. She's heterosexual, but after meeting co-star Lea Seydoux's Emma, falls in love and begins to struggle with her sexuality.

Exarchopoulos said she and Seydoux shared nervous giggles before filming the intimate scenes, but that's it.

"It really developed, there was no choreography at all. We tried to put ourselves in the situation, and it helped in a way that I was new to the situation because my character is new to the situation as well," she said. "So it was alright that I was destabilized. Lea was leading me and I was kind of following in the flow. But I must say it was a strong thing to play."

This is one of two films Seydoux is promoting at this year's festival. The other, "Grand Central," from director Rebecca Zlotowski, is showing in the Un Certain Regard category.

The actress, who cut her hair and dyed it blue for "Adele," said she liked the challenge of her role.

"I really enjoyed playing this part, this tomboy even if it was very difficult sometimes. I like to play parts that are complex, and I like ambiguity and I like contradictions as well, she's like, I like to really give something very subtle," she said.

?Reetu Rupal, http://www.twitter.com/r2today

LI YU CHUN IS BREAKING THE MOLD

Li Yu Chun doesn't exactly mesh with the image of most starlets who walk on the red carpets at the Cannes Film Festival.

Instead of flowing gowns, the Chinese singer has worn dramatic capes that accompany striking pantsuits. And while many female celebrities sport cascading locks, Chun has her hair cut short, pixie style.

"A lot of people are asking me 'Why aren't you wearing a long dress like a princess?'" said Chun, who came to the festival as a representative of the cosmetics brand L'Oreal. "I have another personality and that is why I have to show my own personality with the suits that fit me. That is why I love to work with L'Oreal because they have given me self-confidence."

Chun, who is known for her boyish, androgynous looks, said she was surprised to be chosen as a L'Oreal ambassador since she represents a different look than some of their other representatives at the festival, like Freida Pinto, Julianne Moore, Aishwarya Rai and Eva Longoria.

"Usually they choose girls with long hair and big waves in her hair and that is not exactly my image," she laughed. "That is why I was surprised but happily surprised."

Chun shot to fame when she won "Chinese Best Voices," that country's version of "American Idol. She said she was excited to be in Cannes for the festivities, but was also getting some work done as well.

"I am also participating in their meetings to discuss about how to represent and how to organize promoting events," the 29-year-old said. "They are organizing a lot of activities for me too and this is why I find it very very exciting."

? Sian Watson, http://www.twitter.com/sianwatson

'JIMMY P' ROLES WERE MADE FOR DEL TORO AND AMALRIC ? LITERALLY

For director Arnaud Desplechin, it was either Benicio Del Toro and Mathieu Amalric for "Jimmy P" or no movie.

"I thought if I can't have them, I won't do the film," he said in an interview this week.

Luckily for him, both Benicio Del Toro and Mathieu Amalric said yes to the project.

In "Jimmy P (Psychotherapy of a Plains Indian)," Amalric plays real-life French analyst Georges Devereux, who moved to the United States in the 1930s. He spent time living with Mojave Indians and helped develop the field of ethno-psychiatry, which studies the ways mental illness is understood in different cultural contexts.

Del Toro is his patient Jimmy Picard, who returned from World War II in France with a head injury and debilitating psychological symptoms his doctors were unable to diagnose.

Desplechin said it's the first time he's written a film with actors already in mind.

"I was so nervous when I started it because it was quite difficult to produce because the film is half French, half American, so it was quite tricky," he said. "So before writing it I was thinking who could play in that? I wrote it really for Benicio and Mathieu, they were the two guys."

Reetu Rupal, http://www.twitter.com/r2today

Source: http://news.yahoo.com/seen-heard-cannes-104555429.html

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First drug to significantly improve heart failure mortality in over a decade

May 25, 2013 ? Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality in over a decade and should be added to standard treatment, according to lead author Professor Svend Aage Mortensen (Copenhagen, Denmark).

Heart Failure 2013 is being held from 25-28 May in Lisbon, Portugal. It is the main annual meeting of the Heart Failure Association of the European Society of Cardiology (1).

Coenzyme Q10 (CoQ10) occurs naturally in the body and is essential to survival. CoQ10 works as an electron carrier in the mitochondria, the powerhouse of the cells, to produce energy and is also a powerful antioxidant. It is the only antioxidant that humans synthesise in the body.

CoQ10 levels are decreased in the heart muscle of patients with heart failure, with the deficiency becoming more pronounced as heart failure severity worsens. Statins are used to treat many patients with heart failure because they block the synthesis of cholesterol, but these drugs also block the synthesis of CoQ10, which further decreases levels in the body.

Double blind controlled trials have shown that CoQ10 improves symptoms, functional capacity and quality of life in patients with heart failure with no side effects. But until now, no trials have been statistically powered to address effects on survival.

The Q-SYMBIO study (2) randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 or placebo and followed them for 2 years. The primary endpoint was time to first major adverse cardiovascular event (MACE) which included unplanned hospitalisation due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support. Participating centres were in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.

CoQ10 halved the risk of MACE, with 29 (14%) patients in the CoQ10 group reaching the primary endpoint compared to 55 (25%) patients in the placebo group (hazard ratio=2; p=0.003). CoQ10 also halved the risk of dying from all causes, which occurred in 18 (9%) patients in the CoQ10 group compared to 36 (17%) patients in the placebo group (hazard ratio=2.1; p=0.01).

CoQ10 treated patients had significantly lower cardiovascular mortality (p=0,02) and lower occurrence of hospitalisations for heart failure (p=0.05). There were fewer adverse events in the CoQ10 group compared to the placebo group (p=0.073).

Professor Mortensen said: "CoQ10 is the first medication to improve survival in chronic heart failure since ACE inhibitors and beta blockers more than a decade ago and should be added to standard heart failure therapy."

He added: "Other heart failure medications block rather than enhance cellular processes and may have side effects. Supplementation with CoQ10, which is a natural and safe substance, corrects a deficiency in the body and blocks the vicious metabolic cycle in chronic heart failure called the energy starved heart."

CoQ10 is present in food, including red meat, plants and fish, but levels are insufficient to impact on heart failure. CoQ10 is also sold over the counter as a food supplement but Professor Mortensen said: "Food supplements can influence the effect of other medications including anticoagulants and patients should seek advice from their doctor before taking them."

Patients with ischaemic heart disease who use statins could also benefit from CoQ10 supplementation. Professor Mortensen said: "We have no controlled trials demonstrating that statin therapy plus CoQ10 improves mortality more than statins alone. But statins reduce CoQ10, and circulating CoQ10 prevents the oxidation of LDL effectively, so I think ischaemic patients should supplement statin therapy with CoQ10."

References: 1. Heart Failure Congress 2013 http://www.escardio.org/congresses/hf2013/Pages/welcome.aspx?hit=nav 2. SA Mortensen, A Kumar, P Dolliner, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure. Results from the Q-SYMBIO study. Presented at Heart Failure Congress 2013 Final Programme Number 440. The full title of the Q-SYMBIO study is: "Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised double blind multicentre trial with focus on changes in symptoms, biomarker status with BNP and long term outcome"?

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/d3uGwvq-8wM/130525143852.htm

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Thursday, May 23, 2013

Boeing expects 787 battery retrofits done by next week

WASHINGTON (Reuters) - Boeing Co is 90 percent finished with retrofits of the battery system on its 787 Dreamliner and should finish the rest by next week, Ray Conner, president of the company's commercial airplane division, told an investor conference on Wednesday.

Conner told the conference he saw "great momentum" on the 787 program, after overheated batteries prompted a fleetwide grounding earlier this year.

Production of the new airliner had reached seven airplanes a month and was on track to reach the projected level of 10 per month by the end of the year, Conner said.

Overall, he said the company expected to hit its target of producing 60 Dreamliners by the end of the year.

He said earlier problems with the supply chain had been resolved and the airplane's supply chain was now healthy, Conner said.

"We are turning the corner," Conner said.

(Reporting by Andrea Shalal-Esa; Editing by Gerald E. McCormick and David Gregorio)

Source: http://news.yahoo.com/boeing-says-787-battery-retrofits-done-next-week-145553407.html

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Houston a top market for engineering jobs

Houston is the U.S. market with the greatest need for engineers, a new study says.

Houston was ranked as the No. 1 market in the U.S. with the highest demand for engineers, according to a new Monster Worldwide Inc. (NYSE: MWW) survey.

Following Houston were San Jose, Calif.; San Diego, Calif.; Chicago; and Auburn Hills, Mich.

The Monster survey also revealed that throughout the U.S., the top five engineering occupations are industrial engineer, mechanical engineer, electrical engineer, civil engineer and electronics engineer.

Along the same lines, companies surveyed indicated they were looking for mechanical, electrical, manufacturing and computer skills.

This Monster survey aligns with a longstanding complaint in the Houston market: Energy, manufacturing and technology companies are all clamoring for more engineers.

Recently, there have been a number of new initiatives launched to increase the pipeline of engineers in the market. For example, the Greater Houston Partnership started a regional workforce development task force to help employers attract skilled technical workers to Houston, and Microsoft Corp. launched YouthSpark Houston, a program aimed at increasing the number of skilled science, math, technology and engineering students.

However, while the pipeline is being filled, it may be some time before the demand levels go down.

Molly Ryan covers manufacturing, technology, the Port and logistics.

Source: http://feedproxy.google.com/~r/vertical_30/~3/L34Bsz6lHhQ/houston-ranks-as-no-1-market-for.html

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AP PHOTOS: Devastation, reunion in tornado wake


Essential News from The Associated Press

AAA??May. 21, 2013?10:31 PM ET
AP PHOTOS: Devastation, reunion in tornado wake
By The Associated Press?THE ASSOCIATED PRESS STATEMENT OF NEWS VALUES AND PRINCIPLES?By The Associated Press

A woman walks past a pile of dead horses that were killed in a tornado a day earlier Tuesday, May 21, 2013, in Moore, Okla. A huge tornado roared through the Oklahoma City suburb Monday, flattening entire neighborhoods and destroying an elementary school with a direct blow as children and teachers huddled against winds. (AP Photo/Charlie Riedel)

A woman walks past a pile of dead horses that were killed in a tornado a day earlier Tuesday, May 21, 2013, in Moore, Okla. A huge tornado roared through the Oklahoma City suburb Monday, flattening entire neighborhoods and destroying an elementary school with a direct blow as children and teachers huddled against winds. (AP Photo/Charlie Riedel)

This Tuesday, May 21, 2013 aerial photo shows homes damaged by Monday's tornado in Moore, Oklahoma. The huge tornado roared through the Oklahoma City suburb, flattening entire neighborhoods and destroying an elementary school with a direct blow as children and teachers huddled against winds. (AP Photo/Tony Gutierrez)

An aerial view shows Briarwood Elementary with vehicles thrown about after Monday's tornado, Tuesday, May 21, 2013, in Moore, Okla. At least 24 people, including nine children, were killed in the massive tornado that flattened homes and a school in Moore, on Monday afternoon. (AP Photo/Tony Gutierrez)

Storm clouds build in the distance beyond tornado-ravaged homes Tuesday, May 21, 2013, in Moore, Okla. A huge tornado roared through the Oklahoma City suburb Monday, flattening entire neighborhoods and destroying an elementary school with a direct blow as children and teachers huddled against winds. (AP Photo/Charlie Riedel)

Kandi Scott salvages items from the rubble of her home, which she shared with her mother, until it was destroyed Monday when a tornado moved through Moore, Okla., Tuesday, May 21, 2013. The huge tornado roared through the Oklahoma City suburb, flattening entire neighborhoods and destroying an elementary school with a direct blow as children and teachers huddled against winds.(AP Photo/Brennan Linsley)

Residents sift through the remnants of their homes and parents hug children outside a demolished elementary school. Emergency workers tend to the wounded.

Here are images of the aftermath of a powerful tornado that swept through an Oklahoma City suburb, flattening neighborhoods and killing at least 24 people.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2013-05-21-Oklahoma%20Tornado-Photo%20Gallery/id-8ebdc7ad2cfb4a17a7d76794b7c84a1b

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Wednesday, May 22, 2013

DNA damage: The dark side of respiration

DNA damage: The dark side of respiration [ Back to EurekAlert! ] Public release date: 22-May-2013
[ | E-mail | Share Share ]

Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen

Adventitious changes in cellular DNA can endanger the whole organism, as they may lead to life-threatening illnesses like cancer. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich now report how byproducts of respiration cause mispairing of subunits in the double helix.

The DNA in our cells controls the form and function of every cell type in our bodies. The instructions for this are encoded in the linear sequence of the four subunits found in DNA, the bases adenine (A), cytosine (C), guanine (G) and thymine (T). Random changes in the sequence can lead to cell dysfunction, and may result in unrestricted cell proliferation and malignancies. Mutations can be induced by a variety of agents. For example, cellular respiration, i.e. the reduction of inspired oxygen to water, which powers cell function, also generates highly reactive oxygen species that can damage DNA, with the purine bases G and A being particularly susceptible to this kind of attack.

"Reactive oxygen species are responsible for two different sorts of DNA damage, as they induce formation of both 8-oxo-G and FaPy-G," says Professor Thomas Carell of the Department of Chemistry at LMU. In 2004, work done by Carell and his team defined how 8-oxo-G generates mutations. However, the basis for the mutagenic effect of FaPy-G has remained obscure until now. In their latest publication, Carell and his colleagues describe how FaPY-G leads to mispairing of bases in the double helix.

Pernicious partner swapping

One G in one strand of the double helix normally matches up with a C on the other, forming a G:C pair. But as a consequence of damage by reactive oxygen species, the guanine base may be transformed into FaPy-G, so that we get a FaPy-G:C base pair. "We have now shown that, in the course of DNA replication prior to cell division, FaPy-G interacts with adenine, leading to the formation of FaPy-G:A base pairs. This partner swap is unusual, since unmodified guanine normally does not team up with adenine," Carell notes.

FaPy-G is subsequently recognized as abnormal and is removed by DNA repair enzymes. The missing base is replaced by a T which is the usual partner for A. The net result is that the original G:C base pair has been converted into an A:T pair, and the base sequence has undergone a potentially dangerous mutation.

This outcome is made possible by the fact that the cell's damage-control systems find it surprisingly difficult to distinguish the normal guanine base from its aberrant derivative FaPy-G during DNA replication. "That this defect then leads to mispairing with adenine is one of the main reasons for the spontaneous development of tumors," says Carell. "So with every breath we take, our risk of getting cancer goes up by a teeny-weeny bit." Further insights into the reasons why FaPy-G often eludes the cell's detection and correction systems could help to improve the treatment of cancer, as the inhibition of DNA repair processes in tumor cells increases their sensitivity to chemotherapeutic drugs.

###

The study was supported by DFG grants awarded to Collaborative Research Centers 646 and 749 and the Center for Integrated Protein Science Munich (CIPSM), an Excellence Cluster.


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


DNA damage: The dark side of respiration [ Back to EurekAlert! ] Public release date: 22-May-2013
[ | E-mail | Share Share ]

Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen

Adventitious changes in cellular DNA can endanger the whole organism, as they may lead to life-threatening illnesses like cancer. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich now report how byproducts of respiration cause mispairing of subunits in the double helix.

The DNA in our cells controls the form and function of every cell type in our bodies. The instructions for this are encoded in the linear sequence of the four subunits found in DNA, the bases adenine (A), cytosine (C), guanine (G) and thymine (T). Random changes in the sequence can lead to cell dysfunction, and may result in unrestricted cell proliferation and malignancies. Mutations can be induced by a variety of agents. For example, cellular respiration, i.e. the reduction of inspired oxygen to water, which powers cell function, also generates highly reactive oxygen species that can damage DNA, with the purine bases G and A being particularly susceptible to this kind of attack.

"Reactive oxygen species are responsible for two different sorts of DNA damage, as they induce formation of both 8-oxo-G and FaPy-G," says Professor Thomas Carell of the Department of Chemistry at LMU. In 2004, work done by Carell and his team defined how 8-oxo-G generates mutations. However, the basis for the mutagenic effect of FaPy-G has remained obscure until now. In their latest publication, Carell and his colleagues describe how FaPY-G leads to mispairing of bases in the double helix.

Pernicious partner swapping

One G in one strand of the double helix normally matches up with a C on the other, forming a G:C pair. But as a consequence of damage by reactive oxygen species, the guanine base may be transformed into FaPy-G, so that we get a FaPy-G:C base pair. "We have now shown that, in the course of DNA replication prior to cell division, FaPy-G interacts with adenine, leading to the formation of FaPy-G:A base pairs. This partner swap is unusual, since unmodified guanine normally does not team up with adenine," Carell notes.

FaPy-G is subsequently recognized as abnormal and is removed by DNA repair enzymes. The missing base is replaced by a T which is the usual partner for A. The net result is that the original G:C base pair has been converted into an A:T pair, and the base sequence has undergone a potentially dangerous mutation.

This outcome is made possible by the fact that the cell's damage-control systems find it surprisingly difficult to distinguish the normal guanine base from its aberrant derivative FaPy-G during DNA replication. "That this defect then leads to mispairing with adenine is one of the main reasons for the spontaneous development of tumors," says Carell. "So with every breath we take, our risk of getting cancer goes up by a teeny-weeny bit." Further insights into the reasons why FaPy-G often eludes the cell's detection and correction systems could help to improve the treatment of cancer, as the inhibition of DNA repair processes in tumor cells increases their sensitivity to chemotherapeutic drugs.

###

The study was supported by DFG grants awarded to Collaborative Research Centers 646 and 749 and the Center for Integrated Protein Science Munich (CIPSM), an Excellence Cluster.


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


Source: http://www.eurekalert.org/pub_releases/2013-05/lm-ddt052213.php

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