Raging fire guts Kabul market









KABUL, Afghanistan -- Firefighters battled through the night to contain a raging fire that swept through a market in the Afghan capital.

No injuries were reported, but the blaze destroyed hundreds of stores and millions of dollars worth of merchandise, Afghan police and firefighters said at the scene. 


Dealers at the neighboring currency exchange, the city’s largest, said they evacuated cash, computer equipment and records from their shops as the flames approached during the night. But in the morning, the market was jammed with people haggling over thick stacks of notes as smoke billowed overhead.





Col. Mohammed Qasem, general director of the Kabul fire department, said he suspected an electrical short was to blame for the fire. 


Gas canisters used to heat the stores propelled the flames, along with the cloth and clothing sold by many of the vendors, Qasem said. “It made it very big in a short time.”


Firefighters from the Afghan defense department and NATO forces were sent to assist. But the city’s notorious traffic and the market’s narrow lanes made it difficult for responders to maneuver their vehicles, Qasem said.


Abdulrahman, who like many Afghans has only one name, squatted near a fire truck with his head in his hands  as responders aimed a hose at the blackened ruins of a building still smoldering at noon Sunday, more than 12 hours after the fire broke out.


He said the building had contained three shops that he owned and a warehouse full of glassware, crockery and kitchen utensils. 


“I lost everything,” he said.


Shirali Khan complained that police hadn't allowed him to remove the goods from his four clothing stores.


“They thought we were all robbers,” he said.  “There’s only ashes left.”


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Special correspondent Hashmat Baktash contributed to this report.






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How to Get Free Last-Minute Shipping






First, the bad news: the cut off for free shipping on most online sites was Tuesday, Dec 18th. But the good news – we’ve got some sneaky ways to finagle free rush shipping and a list of sites still offering free shipping guaranteed to arrive before December 25th.


Free Rush Shipping
Some of the biggest online retailers are still offering free last minute shipping:






  • Barnes & Noble – free shipping on Nook HD through Dec. 22

  • MacMall – free 2-day shipping on orders over $ 299 and under 25lbs – through 6 p.m. PST Dec. 22.

  • Macy’s – free shipping on orders over $ 99. Place order 11:59 p.m. EST Dec. 20.

  • The Northface – free 2-day shipping on everything through 11:59 p.m. Dec. 19.

  • Walmart.com has extended free shipping through December 19th on some items (check product page for eligibility)

  • Overstock.com – free shipping on select gifts. Place order by Dec. 22 to receive by Christmas.

  • Newegg   Free 2-Day shipping on over 200 items

  • Target – free shipping on Daily Deals

  • Victoria’s Secret – free shipping on orders over $ 100 using code “SHIP12.” Order by 5 p.m. EST on Dec. 20.

  • Zappos – free shipping for all items with guaranteed Christmas delivery if ordered by 11:59 p.m. PST Dec. 22.

And the biggest of the big online retailers, Amazon, has a limited set of items available for free expedited shipping. These include jewelry, watches, clothing, video games, laptops, headphones, and kitchen items.


[Related: Great Gifts for Under $ 25]


But since many of the above deals are limited to select items, take a look at…


How to Get Free 2-Day Shipping on Just About Everything
Amazon Prime is a yearly subscription service. In exchange for a $ 79 fee, you get free 2 day shipping all year long. And yes, that also applies at Christmas (must order by 3 p.m. EST Dec. 22 to receive on time). Best deal is that you can get a free 6-month trial.a1b8f  free shipping fp How to Get Free Last Minute Shipping


And here’s the real sneaky surprise: Do you have a family member who already belongs to Prime? They can nominate up to four people for the same free shipping benefits. Prime members nominate someone by going to their account, clicking “Settings” and “Manage Prime Membership.”


Also, Amazon Student is a free 6-month membership to Prime with all the benefits, providing you have an email address that ends in .edu.


But you don’t have to limit yourself to Amazon. Shoprunner.com also offers free 2-day shipping, though the membership service costs $ 8.95 a month – so not entirely free, but if you have numerous items still to buy, you could save a bundle.  And Shoprunner has tons of participating online retailers like Toys R Us, Sports Authority, Claire’s, PetSmart and EMS. Say you want to buy something from PetSmart.com, if you sign in with Shoprunner, many of the items on the site will be eligible for free 2-day shipping. One more thing to try: I was able to sign up for a free 1-year membership to Shoprunner using the promo code RUNNER. The site implied I had to be an American Express member, but it never asked for my details about the credit card, and now I have a membership. Good luck.


Ship to Store
Finally, the best last-minute option for many is to ship to store. You peruse all the options from home, pay online, and then pick up your selection at your local store. Tons of big retailers offer this service, and it guarantees your item will be in stock and waiting for you at customer service. Major retailers offering free Ship to Store include:


  • Best Buy

  • Target

  • Toys R Us

  • Walmart

  • Sears

[Related: Best E-Reader for Under $ 100]


Brad Marshland contributed to this story.


Tech News Headlines – Yahoo! News





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'Hobbit' extends No. 1 journey with $36.7 million


LOS ANGELES (AP) — Tiny hobbit Bilbo Baggins is running circles around some of the biggest names in Hollywood.


Peter Jackson's "The Hobbit: An Unexpected Journey" took in $36.7 million to remain No. 1 at the box office for the second-straight weekend, easily beating a rush of top-name holiday newcomers.


Part one of Jackson's prelude to his "The Lord of the Rings" trilogy, the Warner Bros. release raised its domestic total to $149.9 million after 10 days. The film added $91 million overseas to bring its international total to $284 million and its worldwide haul to $434 million.


"The Hobbit" took a steep 57 percent drop from its domestic $84.6 million opening weekend, but business was soft in general as many people skipped movies in favor of last-minute Christmas preparations.


"The real winner this weekend might be holiday shopping," said Paul Dergarabedian, an analyst for box-office tracker Hollywood.com.


Tom Cruise's action thriller "Jack Reacher" debuted in second-place with a modest $15.6 million debut, according to studio estimates Sunday. Based on the Lee Child best-seller "One Shot," the Paramount Pictures release stars Cruise as a lone-wolf ex-military investigator tracking a sniper conspiracy.


Opening at No. 3 with $12 million was Judd Apatow's marital comedy "This Is 40," a Universal Pictures film featuring Paul Rudd and Leslie Mann reprising their roles from the director's 2007 hit "Knocked Up."


Paramount's road-trip romp "The Guilt Trip," featuring "Knocked Up" star Seth Rogen and Barbra Streisand, debuted weakly at No. 6 with $5.4 million over the weekend and $7.4 million since it opened Wednesday. Playing in narrower release, Paramount's acrobatic fantasy "Cirque du Soleil: Worlds Away" debuted at No. 11 with $2.1 million.


A 3-D version of Disney's 2001 animated blockbuster "Monsters, Inc." also had a modest start at No. 7 with $5 million over the weekend and $6.5 million since opening Wednesday.


Domestic business was off for the first time in nearly two months. Overall revenues totaled $112 million, down 12.6 percent from the same weekend last year, when Cruise's "Mission: Impossible — Ghost Protocol" debuted with $29.6 million, according to Hollywood.com.


Cruise's "Jack Reacher" opened at barely half the level as "Ghost Protocol," but with a $60 million budget, the new flick cost about $100 million less to make.


Starting on Christmas, Hollywood expects a big week of movie-going with schools out through New Year's Day and many adults taking time off. So Paramount and other studios are counting on strong business for films that started slowly this weekend.


"'Jack Reacher' will end up in a very good place. The movie will be profitable for Paramount," said Don Harris, the studio's head of distribution. "The first time I saw the movie I saw dollar signs. It certainly wasn't intended to be compared to a 'Mission: Impossible,' though."


Likewise, Warner Bros. is looking for steady crowds for "The Hobbit" over the next week, despite the debut of two huge newcomers — the musical "Les Miserables" and the action movie "Django Unchained" — on Christmas Day.


"We haven't reached the key holiday play time yet," said Dan Fellman, head of distribution for Warner. "It explodes on Tuesday and goes right through the end of the year."


In limited release, Kathryn Bigelow's Osama bin Laden manhunt saga "Zero Dark Thirty" played to packed houses with $410,000 in just five theaters, averaging a huge $82,000 a cinema.


That compares to a $4,654 average in 3,352 theaters for "Jack Reacher" and a $4,130 average in 2,913 cinemas for "This Is 40." ''The Guilt Trip" averaged $2,217 in 2,431 locations, and "Monsters, Inc." averaged $1,925 in 2,618 cinemas. Playing just one matinee and one evening show a day at 840 theaters, "Cirque du Soleil" averaged $2,542.


Since opening Wednesday, "Zero Dark Thirty" has taken in $639,000. Distributor Sony plans to expand the acclaimed film to nationwide release Jan. 11, amid film honors and nominations leading up to the Feb. 24 Academy Awards.


Opening in 15 theaters from Lionsgate banner Summit Entertainment, Naomi Watts and Ewan McGregor's tsunami-survival drama "The Impossible" took in $138,750 for an average of $9,250.


A fourth new release from Paramount, "The Sopranos" creator David Chase's 1960s rock 'n' roll tale "Not Fade Away," debuted with $19,000 in three theaters, averaging $6,333.


Universal's "Les Miserables" got a head-start on its domestic release with a $4.2 million debut in Japan.


Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Where available, latest international numbers are also included. Final domestic figures will be released Monday.


1. "The Hobbit: An Unexpected Journey," $36.7 million ($91 million international).


2. "Jack Reacher," $15.6 million ($2.5 million international).


3. "This Is 40," $12 million.


4. "Rise of the Guardians," $5.9 million ($13.7 million international).


5. "Lincoln," $5.6 million.


6. "The Guilt Trip," $5.4 million.


7. "Monsters, Inc." in 3-D, $5 million.


8. "Skyfall," $4.7 million ($9 million international),


9. "Life of Pi," $3.8 million ($23.2 million international).


10. "The Twilight Saga: Breaking Dawn — Part 2," $2.6 million ($6.6 million international).


___


Estimated weekend ticket sales at international theaters (excluding the U.S. and Canada) for films distributed overseas by Hollywood studios, according to Rentrak:


1. "The Hobbit: An Unexpected Journey," $91 million.


2. "Life of Pi," $23.2 million.


3. "Rise of the Guardians," $13.7 million.


4. "Skyfall," $9 million.


5. "Wreck-It Ralph," $7.3 million.


6. "The Twilight Saga: Breaking Dawn — Part 2," $6.6 million.


7. "Pitch Perfect," $6 million.


8. "Les Miserables," $4.2 million.


9. "Love 911," $3.2 million.


10. "De L'autre Cote du Periph," $3.1 million.


___


Online:


http://www.hollywood.com


http://www.rentrak.com


___


Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.


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Swiss watch sellers gear up for Chinese New Year









Even before the Christmas tree went up at 124-year-old Bucherer watch boutique in the lakeside town of Lucerne, Switzerland, the shop was already planning decorations for the year of the snake.

Chinese symbols marking the start of the lunar new year Feb. 10 will greet the busloads of Asian shoppers who visit Lucerne every day and invite them inside to see watches from Tag Heuer, Rolex and more than 20 other brands.

Less than half the timepieces bought at the Lucerne store in December may be for Christmas, said Joerg Baumann, Bucherer's marketing director.








"Other parts of the year have caught up" with Christmas, Baumann said, "which is good news for retailers because everyone wants a stable business and not an extremely seasonal one."

Asian consumers are easing the Swiss watch industry's reliance on Christmas. While December is still the most important sales period, it's diminishing in importance and may be surpassed by the Chinese New Year within seven years, said Jean-Claude Biver, chairman of LVMH Moet Hennessy Louis Vuitton's Hublot watch brand.

"When I started 38 years ago, December and Christmas were 30% of the business, but that has weakened as sales have become more and more constant during the 12 months," Biver said in his office overlooking Lake Geneva and the French Alps. Christmas now accounts for 15% to 20% of watch industry revenue, he said.

China and Hong Kong make up the biggest market for Swiss timepieces, accounting for 30% of exports of the country's roughly 200 brands in 2011, according to the Federation of the Swiss Watch Industry. Exports to those two destinations rose 10% in the first 10 months of 2012.

Chinese interest in high-end watches remains strong despite concerns about an easing of economic growth, according to research and marketing company Digital Luxury Group. The number of online searches for luxury watch brands in China increased about 40% during the first half of the year, the company said.

Buying watches abroad allows Chinese consumers to sidestep three layers of taxes imposed on watches in China: an 11% import duty, a 20% tax on high-end watches and a 17.5% value-added tax, according to HSBC.

Cie. Financiere Richemont, the maker of Vacheron Constantin and Cartier watches, said last month that the weakness of the euro was luring more Asians to vacation in Europe, helping boost revenue in the region.

"Local consumption in Switzerland is not bad and there's probably even some growth, but the main driver is tourism," said Patrik Schwendimann, an analyst at Zuercher Kantonalbank.

Bucherer's six-story flagship store in Lucerne gives visitors from China greeting cards in red envelopes called hongbao that are supposed to bring luck. A sign at the entrance lists some of the 20-plus languages spoken by sales staff, while display cabinets describe watch features in Chinese.

To cope with the steady stream of Chinese shoppers, about 30 of the roughly 200 staff members speak Mandarin. Bucherer also offers Chinese-language lessons for employees, as well as training on how best to interact with Asian shoppers.

Among the key sales periods for Bucherer, which has more than 20 stores in Switzerland, Germany and Austria, are the week around Chinese national day Oct. 1, as well as Chinese New Year in January or February and the Thai New Year in April, Baumann said.

"The planning starts one year ahead in our themes and how we decorate the stores," Baumann said. "People want to know they're in Switzerland, but it's a little gesture so they're aware we know it's their holiday."

As many as 3,000 Asian tourists a day visit the Bucherer flagship store in Lucerne after sightseeing in the surrounding Alpine landscape. Sales at the shop could reach $1.1 million daily at peak times, said Rene Weber, an analyst at Bank Vontobel in Zurich. The store doesn't disclose revenue.

More than 200,000 visitors from greater China stayed in Lucerne or the surrounding area during the first nine months of this year, more than double the number during the same period in 2007, according to the town's tourism bureau.

The winding streets around Bucherer, lined with ornate, century-old buildings, show the growing importance of Asian tourists. At some watch stores in the area Chinese signs are bigger than those in European languages, and shop windows sometimes display phonetic renderings of brand names in Chinese characters.

Outside Bucherer, mobile phone salesman Zheng Xianjun took in views of the bustling town center and lake after spending about $3,000 for a Longines watch for his wife.

"I'm not buying it for any special occasion," said Zheng, who was visiting from China's Guangdong province. "I don't go abroad all that much and my wife wanted me to get her a watch while I was here."





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Meat company owner sues USDA for right to slaughter horses









Rick de los Santos wants to reopen an animal slaughter business that's been banned in the U.S. for years. Along the way, he's also opened a can of worms.


The Roswell, N.M., meat company owner sued the federal government last week, alleging that officials ignored his application to resume domestic horse slaughter for food because the practice had become an emotional political issue throughout the West.


After waiting a year for permits, De los Santos, 52, says he's using the courts to force the U.S. Department of Agriculture to resume inspections necessary to open what would be the nation's first new horse slaughterhouse since 2007.





"I've submitted all the paperwork and have been told all along 'Oh, it won't be long now,'" said De los Santos, who owns Valley Meat Co. "I followed all their guidelines. I put more than $100,000 in upgrades and additions on my facilities to handle equine slaughter. And then the government comes back and tells me, 'We can't give you the permits. This horse issue has turned into a political game.'


"So what else do you do? I figured it was time to go to court."


The slaughterhouse owner, whose business had been slaughtering cattle, is also suing the Humane Society of the United States, Front Range Equine Rescue and Animal Protection of New Mexico, accusing those groups of defamation and causing loss of income during the dispute.


The dispute over killing horses has raged for years. Equine advocates have accused the Bureau of Land Management of failing to protect tens of thousands of mustangs that wander government-owned land in 10 Western states. Many of the animals are corralled each year and sent to long-term holding facilities. And reports surfaced this fall that the BLM was knowingly selling wild horses for slaughter, an outcome banned annually by Congress. The agency is investigating the claim.


In 2007, the last three domestic slaughterhouses in the United States were closed. Since then, unwanted domestic animals have been shipped to Mexico and Canada for slaughter.


Many animal protection groups and public officials were outraged at the idea of resuming domestic horse slaughter, including New Mexico Gov. Susana Martinez, a Republican, who has opposed the plan.


Many animal advocates says horse slaughter has no business in the U.S.


"Everything is wrong with this idea," said Sally Summers, founder of Horse Power, a Nevada-based equine advocacy group. "The economy has done just fine without this type of slaughter. And these plants are toxic to the community. They hurt these towns; they don't help them."


Summers said that many of the drugs that U.S. owners give their horses to ensure longevity and peak performance are carcinogenic. "This stuff gets into the water table through the drains," she said. "It's a nightmare. This man is smoking a pipe and I don't know what's in it."


The USDA declined to comment last week on the pending litigation. The agency has until January to respond to the suit, filed in federal court in late October.


De los Santos says his lawsuit will show that a recent "marked change in cooperation" by the USDA is due to pressure the government is receiving on the horse issue.


Some support a return to domestic horse slaughter. The American Quarter Horse Assn. says a 2011 report from the federal Government Accountability Office shows horse abuse and abandonment have been increasing since Congress essentially banned horse slaughter by cutting funding for USDA inspection programs in 2006.


The number of U.S. horses sent to other countries for slaughter has nearly tripled since domestic horse slaughter ceased. Most animal advocacy groups agree that some of the worst abuse occurs in the slaughter pipeline that often takes horses to inhumane facilities in Mexico.


Last year, 68,429 horses were shipped to Mexico and 64,652 to Canada, according to USDA statistics compiled by the Equine Welfare Alliance, a nonprofit group dedicated to ending horse slaughter. That compares with total exports of 37,884 of the animals in 2006.


De los Santos says he is tired of sitting in southern New Mexico and watching countless truckloads of horses en route to Mexico for slaughter.


"I've seen 130,000 horses a year on their way to Mexico — they go right through our backyard — and I wanted to tap into the market," he said. "I could have hired 100 people by now. Everyone in our community agrees we need this type of service. And I'm tired of waiting."


De los Santos says he is ready to start killing horses humanely.


"Everything that has four legs that walks can be slaughtered the same way, but we're ready to do this humanely," he said. "We've upgraded our knocking chutes for giving them that lethal hit."


He says he can't understand why everyone is so upset. Americans kill cows; why not horses?


"My wife says horse is on the menu all over Europe, but the moment you mention horse slaughter in the U.S., you've got a problem," he says.


john.glionna@latimes.com





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Facebook Poke App Is Frustrating as Hell






Facebook Poke: Startup Screen


Poke, the new iPhone app from Facebook, lets you send short messages, photos and videos to friends that automatically self destruct after a few seconds. If you have the Facebook app on your phone already, logging in is effortless.


Click here to view this gallery.






[More from Mashable: 2012′s Biggest Winners and Losers]


I was never a big poker on Facebook. When I joined the social network in 2007, giving someone a “poke” was still pretty common. It was a connection that stopped short of an actual friend request, a way to test the waters of a reconnection with, say, an ex.


The new app, Facebook Poke (as it’s listed in the App Store), doesn’t have much in common with poking of old. It’s essentially a clone of other texting apps where all the messages have a built-in self-destruct. It’s ideal for clandestine activities, shall we say.


[More from Mashable: Facebook Introduces Snapchat Competitor, Poke]


Here’s how it works: Let’s say you have a sudden urge to send one of your Facebook friends a photo of a, er, cucumber. But you don’t want to just send them a cucumber pic that they could post and re-share to the world. Poke lets you send the pic, but the recipient will only have 1, 3, 5 or 10 seconds to view your majestic vegetable. And they need to press and hold the screen while viewing, or the pic goes away.


You can send photos, videos or text messages via Poke, although you can’t use it for anything too elaborate since the message content lasts 10 seconds maximum. After that, boom. The message, whatever it was, is gone forever. There isn’t even a record on the sender’s phone (although a log of who you’ve poked and who’s poked you still remains).


Poke is pretty unforgiving. The recipient must press and hold the notification to see the content. Once you touch, the countdown starts, and there’s no going back — even if you let go. Videos just stop, with no chance of re-watching. You slip, and you’re done.


I suspect Poke will engender a lot of frustration because of this limitation. You feel as if it should at least pause the countdown when you remove your finger.


The app also lets you just “poke” people — meaning send a message with no content — about the only way the app is similar to the old act of poking. Those are just simple notifications, and don’t expire.


It gets more annoying: All your poke recipients need to download the app to see them. Poking only works on mobile right now, and Facebook’s been careful to ensure notifications for incoming pokes only appear in its mobile apps.


Checking out your profile on the web won’t reveal any trace of poking. On a smartphone, a note appears that encourages pokees to download the app.


What if someone does a screengrab of your poke, turning it into something more permanent? There’s nothing you can do, but the app will inform you if someone does that, with a “flash” icon beside their name in your feed. If you see your ephemeral wild moment appear on Tumblr the next day, at least you’ll know who to blame.


Poke isn’t that intuitive. It displays some basic instructions when you first log in, but would benefit greatly from one of those tutorial overlays that have become ubiquitous among iOS apps. Also, I find it odd that your front-facing camera isn’t selected by default. But maybe my expectation for the subject material of most pokes is off the mark.


You can add text and colored line drawings to any pics you send. That’s helpful to get the attention on the thing in the photo you really want the person to look at in those three seconds of poke life.


At first I found it frustrating that Poke doesn’t let you take horizontal photos or videos. But that’s actually a good idea. If you think about it, if the only people seeing this content are people glancing at their phones for a few seconds, so vertical pics make total sense. In the time it took a person to turn their phone and the accelerometer to react, the message will probably be gone. If you want masterpieces, try Flickr.


Bottom line: Poke is an annoying app, but it probably has more to do with the nature of what it’s trying to do than any design flaws. How do you like Poke? Let us know in the comments.


Image courtesy of iStockphoto, jcsmily


This story originally published on Mashable here.


Tech News Headlines – Yahoo! News





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Ashton Kutcher files for divorce from Demi Moore


LOS ANGELES (AP) — Ashton Kutcher filed court papers Friday to end his seven-year marriage to actress Demi Moore.


The actor's divorce petition cites irreconcilable differences and does not list a date that the couple separated. Moore announced last year that she was ending her marriage to the actor 15 years her junior, but she never filed a petition.


Kutcher's filing does not indicate that the couple has a prenuptial agreement. The filing states Kutcher signed the document Friday, hours before it was filed in Los Angeles Superior Court.


Kutcher and Moore married in September 2005 and until recently kept their relationship very public, communicating with each other and fans on the social networking site Twitter. After their breakup, Moore changed her name on the site from (at)mrskutcher to (at)justdemi.


Kutcher currently stars on CBS' "Two and a Half Men."


Messages sent to Kutcher's and Moore's publicists were not immediately returned Friday.


Moore, 50, and Kutcher, 34, created the DNA Foundation, also known as the Demi and Ashton Foundation, in 2010 to combat the organized sexual exploitation of girls around the globe. They later lent their support to the United Nations' efforts to fight human trafficking, a scourge the international organization estimates affects about 2.5 million people worldwide.


Moore was previously married to actor Bruce Willis for 13 years. They had three daughters together — Rumer, Scout and Tallulah Belle — before divorcing in 2000. Willis later married model-actress Emma Heming in an intimate 2009 ceremony at his home in Parrot Cay in the Turks and Caicos Islands that attended by their children, as well as Moore and Kutcher.


Kutcher has been dating former "That '70s Show" co-star Mila Kunis.


The divorce filing was first reported Friday by People magazine.


___


Anthony McCartney can be reached at http://twitter.com/mccartneyAP.


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Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


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Naomi Gleit helps keep Facebook growing









The gig: As senior director of Facebook Inc.'s growth, engagement and mobile team, Naomi Gleit helps grow the social network's 1-billion-plus user base.


Facebook employee No. 29: Few people outside Facebook have heard of Gleit, but she's the second-longest-serving Facebook employee, after Facebook founder Mark Zuckerberg. Gleit, 29, talked her way into a job at Facebook on July 18, 2005 — her birthday. She was Facebook's 29th employee, coming on board shortly after the company hit 1 million users and before anyone had an inkling of the colossus it would become.


Dogged spirit: Unlike most other early employees who eventually dispersed to seek new fortunes, Gleit says she has no intention of leaving Facebook. She gets that tenacity from her "tiger mom," a computer programmer who ferried her to ballet, piano, karate and Chinese lessons, and her Jewish father, an immigration lawyer who took her to Hebrew school, she said. "I know it sounds completely irrational, but I had no doubt in 2005 that Facebook would be something incredible in the future," she said.





Rival social networks: Her passion for Facebook began before she was hired, when she was a Stanford undergraduate studying science, technology and society, an interdisciplinary major. She wrote her senior thesis on why Facebook beat out rival college social networking site Club Nexus at Stanford. (Club Nexus was started by Stanford student and Turkish software engineer Orkut Büyükkökten, who went on to create Orkut, Google's first attempt at a social network.) Getting in on the ground floor at Facebook made her feel like she was taking part in something bigger than herself, the same feeling she got volunteering for six months in a refugee camp in Botswana, she said.


Growing with Facebook: Gleit helped Facebook push beyond colleges to high schools and eventually to everyone. In late 2007, when the torrid growth pace temporarily cooled, Zuckerberg tapped a team of five to reignite it and asked Gleit to lead product management. It fell to the growth team to identify the obstacles to the company's momentum. In a company ruled by engineers, Gleit, who never studied programming, earned respect with her analytical approach and intuitive understanding of people. "I always believed that growth was the most important thing, the most important way to impact the company," she said. There are now more than 150 people on the team. "It's been an incredible learning experience," she said. "Each year is different."


That magic moment: Those who work closely with Gleit say part of her success early on was her ability to seize on the "magic moment" that makes users fall in love with Facebook. She made it simpler to sign up, and she helped people find friends as soon as they joined. She also helped Facebook spread quickly to new countries by enlisting users to translate the service into more than 80 languages. Gleit helps her team parachute into new markets and traverse less-familiar languages and cultures. It's something that comes from her own passion to see the world and have new experiences. She has taught on a Navajo reservation and lived in a Buddhist monastery in Thailand.


One billion users: Around noon Sept. 14, Zuckerberg gathered with Gleit and dozens of employees in front of a big screen as the number of Facebook users crossed 1 billion. "The scale was insane," she said. "But that is not the goal. When Mark talks about his vision for Facebook, he talks about being able to connect everyone in the world to the people that they care about and provide some value for them every single day."


A problem solver: Zuckerberg calls on Gleit for high-profile projects. In May 2010, when Facebook was under siege because of how it was handling users' personal information, he put Gleit in charge of simplifying privacy settings. Last year she worked on a popular feature that lets users subscribe to a News Feed without having to become Facebook friends.


Betting on mobile: Now Gleit is focused on the future: mobile devices and how they can unlock emerging markets. Gleit knew back in 2011 that people would begin to log on to Facebook from mobile devices in greater numbers than from desktops, particularly in the developing world. So she traveled to Tel Aviv to buy Snaptu, which makes software that helps people on low-tech phones access Facebook, and she brought the whole team back to Silicon Valley with her. Now Facebook is surging in popularity on mobile devices in Tokyo and Nairobi, Kenya. "I have always been interested in technology and how it can be used to improve lives," Gleit said.


jessica.guynn@latimes.com





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Violence in America? We're all responsible









For years, the National Rifle Assn. has been telling us that guns don't kill people, people kill people.


In the wake of the Newtown shootings, the group has added a twist. Guns don't kill people; television, film and video games do.


Breaking its days-long silence, the NRA on Friday offered its solution to making American schools safer — armed guards — and laid the blame for the seemingly endless cycle of mass shootings on "a callous, corrupt and corrupting shadow industry that sells, and sows, violence against its own people."





PHOTOS: Mourning after the massacre


That would be the entertainment industry, which as Wayne LaPierre, the NRA's vice president, went on to explain, creates violent video games, films and television shows that inundate our youth with "the filthiest form of pornography."


Citing, rather inexplicably, old films including "American Psycho" (which was an adaptation of a novel), the NRA condemned Hollywood for its addiction to violence.


This is a complete cultural contradiction. If we are to be a society that celebrates firepower, that believes the answer to violence is violence, then it would follow that our art forms would reflect that.


Which, of course, we are and which, of course, they do. As far apart as the NRA and Hollywood may seem from each other politically, they are two of the more powerful forces affecting popular culture. Intentionally or not, their relationship is symbiotic.


As we have been told repeatedly during the last week, the gun lobby is among the most powerful in Washington, able to cow politicians and presidents into policy often in direct opposition to their personal and publicly stated opinions.


The ban on assault weapons was allowed to lapse because even President Obama, so often labeled as ultra-liberal, didn't want to waste his currency of compromise in a fight he didn't think he could win. And so, as pointed out in a Times opinion piece by U.S. District Judge Larry Alan Burns, who made a conservative jurist's case for an assault weapons ban after sentencing Tucson shooter Jared Lee Loughner, half of the nation's deadliest shootings occurred after the ban expired, including the massacre at Sandy Hook Elementary.


FULL COVERAGE: Connecticut school shooting


Yet to the NRA, the real villain is the entertainment industry, with its serial-killer serials, bang-bang franchises and first-person shooter video games. Never mind the wide availability of military-style assault weapons; "Batman" and "Call of Duty," the gun lobby would have us believe, is more to blame for all the recent mass shootings. Reality is merely imitating art.


There is no denying that there is too much violence in film and television today, too many video games centered around high and bloody body counts. But how could this not be the case? We live in a country where the suggestion that civilians should not be able to own weapons designed to kill a large number of people quickly is inevitably dubbed as unconstitutional.


The NRA believes that the ability to own guns and use guns defines us as Americans. So how can it blame Hollywood for creating the kind of films and television shows that do precisely the same thing?


No doubt Hollywood will respond swiftly with words we've heard before — violence is essential to drama, art is a way to diffuse the aggressive tendencies we naturally have, imagery cannot become reality if the weapons aren't available, etc., etc. We will be treated, no doubt, to the sight of two self-important, overly influential groups standing on either side of 26 utterly inexcusable graves, pointing fingers at each other.


Accusations of making a national tragedy political have already begun, but it's actually worse than that. We're just making it theatrical, with all the usual suspects reciting all the usual lines, criminally diminishing the lives taken at Sandy Hook to a posturing rerun.


We have all failed. As Americans, as adults, as human beings. As creators and consumers, as politicians and voters. If 20 first-graders shot in their classroom is not proof that things have gotten out of control, then it's hard to imagine what is. Both sides, all sides, need to take responsibility.


Trumpeting a "more is more" mentality, Americans find it increasingly difficult to contemplate the restriction of anything; many of us can't even lose the weight that threatens our lives. The NRA's suggestion that what we really need is armed guards at schools sacrifices not just the notion of a peacetime nation (the terrorists have indeed won, except the terrorists are us) but of civilization itself. Are we really willing to return to the days of the Wild West?


But their point about our art forms, though posed rather hysterically, is not without truth. Too many of our prestige TV shows, our blockbuster films and our popular games revolve around violence. More important, they celebrate people and actions we would deplore in real life.


And while there is value in exploring the outer limits of both human valor and depravity, there is also such a thing as wallowing, of substituting shock for illumination. A high body count, a charming psychopath, should not be a prerequisite for a hit film or show.


In Ang Lee's beautiful film "The Ice Storm," adults argue and engage in endlessly self-absorbed drama while one of their children, unnoticed, forgotten, walks down an empty frozen street, where a power line falls and electrocutes him.


This is not the time for the grown-ups to argue; we have been arguing for far too long, and while we argue, our children die. This is the time for us all to take responsibility, make it not so easy for a young man to imagine a hideous act of violence, and not so easy for him to actually commit it.


mary.mcnamara@latimes.com







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