Jessica Simpson's Christmas gift: She's pregnant


NEW YORK (AP) — Jessica Simpson's daughter has the news all spelled out: "Big Sis."


Simpson on Tuesday tweeted a photo of her baby daughter Maxwell playing in the sand, the words "Big Sis" spelled out.


The 32-year-old old singer and personality has been rumored to be expecting again. The tweet appears to confirm the rumors.


"Merry Christmas from my family to yours" is the picture's caption. Simpson used a tweet on Halloween in 2011 to announce she was pregnant with Maxwell. She is engaged to Eric Johnson and gave birth to Maxwell in May.


One possible complication regarding her pregnancy: She is a spokeswoman for Weight Watchers.


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Vaulting into car history at the Petersen museum









Chris Brown's voice is giddy as the elevator in the Petersen Automotive Museum begins its descent to the basement. He is as excited as his visitors, but before the doors open he strikes a tone of caution.


"No touching, no photos and watch your step," he says. "Old cars are like little dogs: They tend to leave puddles."


The group chuckles nervously and follows him down a corridor lit by dim fluorescent lights into an enormous cavern filled with hundreds of neatly parked cars.





Brown, 38, is the museum's marketing director, but today he's exchanged suit and tie for a black racing jacket with "Petersen Museum" emblazoned in red letters on the back. Like an impresario, he faces his visitors and gestures out over the showroom, a place that has a nearly legendary status among automotive insiders around the world, a place known as the vault.


Taking up a city block on Wilshire Boulevard's Museum Row, the Petersen has drawn visitors since 1994. Its collection is considered one of the finest in the country, with detailed dioramas and presentations that provide historic and cultural context.


The vault — once restricted to high-ranking museum personnel and visiting VIPs, but now open to the public through Jan. 6 — is far different than the galleries upstairs. Inside, in a space the size of a football field, are 150 cars parked as if in a city lot. There are no special displays with manikins, velvet ropes and faux boulevards.


Many of the cars have been displayed at other times in the museum, but to see them in such simple circumstance is a chance to appreciate the swoop of a fender, the rake of a radiator grille or the grain of a leather interior.


"When you see a car upstairs," said Jay Leno, who visited the vault before its opening, "it's all polished up and roped off and everything. For a car guy like me, I prefer to walk up to a car and see it without all the pomp and circumstance."


Brown begins the hourlong tour following a clockwise pattern. To his right is a black 1952 Ferrari Barchetta once owned by Henry Ford. Behind him is the burgundy 1953 Cadillac coupe that Prince Aly Khan gave to Rita Hayworth. Herbie the Love Bug is against a far wall.


The tour group huddles in close so as not to miss a word. Stopping before a black Lincoln with undulating front fenders that hang over brilliant whitewalled tires, Brown raises a hand for dramatic effect.


"It was the first armored car ever commissioned for White House service," Brown says, his voice bouncing off the concrete walls.


Ordered the day after the attack on Pearl Harbor for President Franklin D. Roosevelt, the 1942 Lincoln was built with steel plating nearly a quarter-inch thick and has windows made up of nine panes of laminated glass.


Craig Parry, visiting from Morganville, Kan., is impressed. He is with his wife, Terri, and their son David. They hadn't intended to visit the vault but thought it would be an opportunity to see history. Crossing his arms, he looks out over the collection.


"I've never seen or heard of many of the cars they have here," Parry said. "We got lucky."


At a time when museums across the country are struggling to boost attendance, Petersen officials know the value of their collection and are eager to capitalize on any aspect of it that might increase the visitor count.


Terry Karges came up with the idea of marketing the vault (tours cost $25 on top of the museum's $12 admission fee). He is the executive director of the Petersen, and when he was hired in August he realized that he had a challenge. There was a time when Petersen officials hoped to draw 400,000 visitors a year. At best, the museum has succeeded in drawing half that number. Karges believes the problem has been underexposure.


"The Petersen is largely considered to be the crown jewel of automotive museums," he said. "You just stand back and say, 'There's so much more we can do to attract people.'"


Automobile museums are a hard sell.


"All museums have to get creative to bring in those crowds — whether that's a new exhibit, or opening the vault, whatever," said Jackie L. Frady, executive director of the National Automobile Museum in Reno and president of the National Assn. of Automobile Museums.


In Reno, Frady oversaw an exhibit that featured a group of wild cars from the Burning Man festival, including one automobile that resembled a plump baked potato and another that looked like two matching pink bunny slippers.





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Dueling Santa trackers are off and running













Google's Santa Tracker


A screen grab from Google's Santa Tracker.
(Google / December 24, 2012)





































































All year long Santa keeps an eye on you. Now it's time to turn the tables.


One day a year, you are invited to keep an eye on Santa as he whips around the world in his sleigh, delivering a dizzying number of presents to children all over the world.


If you'd like to see where Santa is at the moment, you've got choices. Google and NORAD, which used to team up for your Santa tracking pleasure, have gone their separate ways this year and created two distinct tracking options.





Google's Santa Tracker is the slicker of the two. It takes you to Santa's Dashboard, where you can see Santa's current location, his next location, the number of miles traveled, and the number of presents delivered. Santa is also adding Twitter like status updates. The most recent one as of this writing: "Rudolph's nose just turned red." 


PHOTOS: Google Doodles of 2012


You can also click on the map and see where Santa has been, as noted by little present icons on the map. Click on the icon and you'll see how many presents Santa has delivered in each city. When Santa is on the move, you'll see him flying on the map in a sleigh. When he's stopped to deliver presents, you'll see him shoving presents down a chimney.


Over at the official NORAD Tracks Santa website you'll also find a running tally of how many presents Santa has delivered as well as what city he just left and what city he's currently headed toward. NORAD also offers Santa Cams that show animations of Santa flying around the world. 


Both Santa tracking services offer loads of extras. If you visit Santa's Village on Google's tracker you can send a message from  Santa to a friend or family member. And NORAD has more than 1,200 volunteers staffing a Santa hotline to answer all your Santa questions.  (877-HI-NORAD).


In the spirit of the season you might try them both out, but hurry up. The trackers shut down a few hours before Christmas morning. 


Happy tracking!


ALSO:


Rumored iPad 5 to be thinner -- and land in March



Battle of the Santa trackers: Google takes on NORAD


Google+

deborah.netburn@latimes.com

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Thousands sign US petition to deport Piers Morgan


LONDON (AP) — Tens of thousands of people have signed a petition calling for British CNN host Piers Morgan to be deported from the U.S. over his gun control views.


Morgan has taken an aggressive stand for tighter U.S. gun laws in the wake of the Newtown, Connecticut, school shooting. Last week, he called a gun advocate appearing on his "Piers Morgan Tonight" show an "unbelievably stupid man."


Now, gun rights activists are fighting back. A petition created Dec. 21 on the White House e-petition website by a user in Texas accuses Morgan of engaging in a "hostile attack against the U.S. Constitution" by targeting the Second Amendment. It demands he be deported immediately for "exploiting his position as a national network television host to stage attacks against the rights of American citizens."


The petition has already hit the 25,000 signature threshold to get a White House response. By Monday, it had 31,813 signatures.


Morgan seemed unfazed — and even amused — by the movement.


In a series of Twitter messages, he alternately urged his followers to sign the petition and in response to one article about the petition said "bring it on" as he appeared to track the petition's progress.


"If I do get deported from America for wanting fewer gun murders, are there any other countries that will have me?" he wrote.


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News Analysis: Getting Polio Campaigns Back on Track





How in the world did something as innocuous as the sugary pink polio vaccine turn into a flash point between Islamic militants and Western “crusaders,” flaring into a confrontation so ugly that teenage girls — whose only “offense” is that they are protecting children — are gunned down in the streets?




Nine vaccine workers were killed in Pakistan last week in a terrorist campaign that brought the work of 225,000 vaccinators to a standstill. Suspicion fell immediately on factions of the Pakistani Taliban that have threatened vaccinators in the past, accusing them of being American spies.


Polio eradication officials have promised to regroup and try again. But first they must persuade the killers to stop shooting workers and even guarantee safe passage.


That has been done before, notably in Afghanistan in 2007, when Mullah Muhammad Omar, spiritual head of the Afghan Taliban, signed a letter of protection for vaccination teams. But in Pakistan, the killers may be breakaway groups following no one’s rules.


Vaccination efforts are also under threat in other Muslim regions, although not this violently yet.


In Nigeria, another polio-endemic country, the new Islamic militant group Boko Haram has publicly opposed it, although the only killings that the news media have linked to polio were those of two police officers escorting vaccine workers. Boko Haram has killed police officers on other missions, unrelated to polio vaccinations.


In Mali, extremists took over half of the country in May, declaring an Islamic state. Vaccination is not an issue yet, but Mali had polio cases as recently as mid-2011, and the virus sometimes circulates undetected.


Resistance to polio vaccine springs from a combination of fear, often in marginalized ethnic groups, and brutal historical facts that make that fear seem justified. Unless it is countered, and quickly, the backlash threatens the effort to eradicate polio in the three countries where it remains endemic: Pakistan, Afghanistan and Nigeria.


In 1988, long before donors began delivering mosquito nets, measles shots, AIDS pills, condoms, deworming drugs and other Western medical goods to the world’s most remote villages, Rotary International dedicated itself to wiping out polio, and trained teams to deliver the vaccine.


But remote villages are often ruled by chiefs or warlords who are suspicious not only of Western modernity, but of their own governments.


The Nigerian government is currently dominated by Christian Yorubas. More than a decade ago, when word came from the capital that all children must swallow pink drops to protect them against paralysis, Muslim Hausas in the far-off north could be forgiven for reacting the way the fundamentalist Americans of the John Birch Society did in the 1960s when the government in far-off Washington decreed that, for the sake of children’s teeth, all drinking water should have fluoride.


The northerners already had grievances. In 1996, the drug company Pfizer tested its new antibiotic, Trovan, during a meningitis outbreak there. Eleven children died. Although Pfizer still says it was not to blame, the trial had irregularities, and last year the company began making payments to victims.


Other rumors also spring from real events.


In Pakistan, resistance to vaccination, low over all, is concentrated in Pashtun territory along the Afghan border and in Pashtun slums in large cities. Pashtuns are the dominant tribe in Afghanistan but a minority in Pakistan among Punjabis, Sindhis, Baluchis and other ethnic groups. Many are Afghan refugees and are often poor and dismissed as medieval and lawless.


Pakistan’s government is friendly with the United States while the Pashtuns’ territory in border areas has been heavily hit by American Taliban-hunting drones, which sometimes kill whole families.


So, when the Central Intelligence Agency admitted sponsoring a hepatitis vaccination campaign as a ruse to get into a compound in Pakistan to confirm that Osama bin Laden was there, and the White House said it had contemplated wiping out the residence with a drone missile, it was not far-fetched for Taliban leaders to assume that other vaccinators worked for the drone pilots.


Even in friendly areas, the vaccine teams have protocols that look plenty suspicious. If a stranger knocked on a door in Brooklyn, asked how many children under age 5 were at home, offered to medicate them, and then scribbled in chalk on the door how many had accepted and how many refused — well, a parent might worry.


In modern medical surveys — though not necessarily on polio campaigns — teams carry GPS devices so they can find houses again. Drones use GPS coordinates.


The warlords of Waziristan made the connection specific, barring all vaccination there until Predator drones disappeared from the skies.


Dr. Bruce Aylward, a Canadian who is chief of polio eradication for the World Health Organization, expressed his frustration at the time, saying, “They know we don’t have any control over drone strikes.”


The campaign went on elsewhere in Pakistan — until last week.


The fight against polio has been hampered by rumors that the vaccine contains pork or the virus that causes AIDS, or is a plot to sterilize Muslim girls. Even the craziest-sounding rumors have roots in reality.


The AIDS rumor is a direct descendant of Edward Hooper’s 1999 book, “The River,” which posited the theory — since discredited — that H.I.V. emerged when an early polio vaccine supposedly grown in chimpanzee kidney cells contaminated with the simian immunodeficiency virus was tested in the Belgian Congo.


The sterilization claim was allegedly first made on a Nigerian radio station by a Muslim doctor upset that he had been passed over for a government job. The “proof” was supposed to be lab tests showing it contained estrogen, a birth control hormone.


The vaccine virus is grown in a broth of live cells; fetal calf cells are typical. They may be treated with a minute amount of a digestive enzyme, trypsin — one source of which is pig pancreas, which could account for the pork rumor.


In theory, a polio eradicator explained, if a good enough lab tested the vaccine used at the time the rumor started, it might have detected estrogen from the calf’s mother, but it would have been far less estrogen than is in mother’s milk, which is not accused of sterilizing anyone. The trypsin is supposed to be washed out.


In any case, polio vaccine is now bought only from Muslim countries like Indonesia, and Muslim scholars have ruled it halal — the Islamic equivalent of kosher.


Reviving the campaign will mean quelling many rumors. It may also require adding other medical “inducements,” like deworming medicine, mosquito nets or vitamin A, whose immediate benefits are usually more obvious.


But changing mind-sets will be a crucial step, said Dr. Aylward, who likened the shootings of the girls to those of the schoolchildren in Newtown, Conn.


More police involvement — what he called a “bunkerized approach” — would not solve either America’s problem or Pakistan’s, he argued. Instead, average citizens in both countries needed to rise up, reject the twisted thinking of the killers and “generate an understanding in the community that this kind of behavior is not acceptable.”


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Online holiday shoppers spent $1 billion on 'Free Shipping Day'









Shoppers scrambling to buy last-minute presents but avoid the malls spent $1.01 billion on this year's Free Shipping Day.


The annual event is scheduled to take place on the last day that orders delivered by ground can be guaranteed to arrive by Christmas. This year, that was Monday, Dec. 17, when more than 1,000 retailers offered free shipping.


Free Shipping Day was the beginning of a hectic workweek for online merchants, who raked in $3.69 billion during last week's five weekdays, up 53% from the same period last year, according to research firm ComScore.





"The fact that Free Shipping Day occurred on a Monday, combined with the fact that so many retailers extended their promotions into the middle of the week -- with guaranteed shipping by Christmas -- helped deliver an encouraging late-season surge," said ComScore Chairman Gian Fulgoni.


The busiest online shopping day of the year was again Cyber Monday -- Nov. 26 this year -- with a record $1.47 billion of spending, followed by Tuesday, Dec. 4, and then Dec. 10 (also known as Green Monday).


During the holiday shopping season online retailers racked up a dozen days that each surpassed more than $1 billion in spending, topping last year's total of 10 days.


ALSO:


Stores offer same-day delivery to compete with Amazon


Best Buy extends deadline for founder to make takeover bid


Stores hope last-minute Christmas shoppers revive holiday sales


Follow Shan Li on Twitter @ShanLi





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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.”


ALSO:


Pope pardons former butler convicted of theft


Bombing kills local official, 7 other people in Pakistan


Tensions high as vote on proposed Egyptian constitution continues


Special correspondent Hashmat Baktash contributed to this report.






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RIM’s biggest problem: It’s still scrambling to catch yesterday’s hottest mobile app






The moment I first realized that RIM (RIMM) was truly in enormous trouble was back in 2010 when I heard then co-CEO Jim Balsillie downplay the importance of apps. Yes, you read that correctly. Balsillie actually told attendees at a Web 2.0 summit in 2010 that the Internet itself was the most important “app” for mobile devices and contended that the “Web needs a platform that allows you to use your existing Web content, not apps.” My feelings on this matter were only solidified when I attended the BlackBerry World conference in May 2011 and watched RIM executives proudly announce that the Playbook tablet would soon get its own version of Angry Birds sometime in the near future. In reality, Angry Birds didn’t release for BlackBerry until late December of that year, or two full years after it was originally released for iOS.


[More from BGR: WhatsApp goes free for iPhone for a limited time]






All of which brings me back to RIM’s current state: Despite the great looking hardware and user interface pictures we’ve seen from new BlackBerry 10 smartphones so far, the company still has an app problem. I was reminded of this when I read a post over at CrackBerry titled, “There’s still a chance for WhatsApp on BlackBerry 10.” The issue here isn’t whether RIM eventually does or doesn’t get WhatsApp on its platform — the issue is that RIM always seems to be one step behind when it comes to getting the hottest apps of the day on its devices.


[More from BGR: BlackBerry 10 browser smokes iOS 6 and Windows Phone 8 in comparison test [video]]


The most absurd example of this, of course, is Instagram. Yes, it’s very likely that BlackBerry 10 will support the popular photo-sharing app right out of the gate given the company’s partnership with Instagram owner Facebook (FB). But we still have no official confirmation that Instagram will be a BlackBerry 10 app just over a month before the new platform launches, and this is symbolic of the fact that RIM is always stuck at the back of line when it comes to app developers’ priorities.


Simply put, RIM can’t possibly hope to compete with Android, iOS or even Windows Phone 8 if its users will always wonder if they’ll be able to do all the cool things with their phones that their friends can do. In the unpredictable Wild West of today’s app market, where new apps seemingly go viral overnight to become global powerhouses, platform developers need to make sure they have quick and simple ways for app developers to port over their software. And until RIM figures out a way to get this done, it still has no shot in the long term.


This article was originally published by BGR


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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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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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