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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'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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Association board can't use email instead of meetings

Question: I recently was elected to the board of directors of my homeowners association. I was surprised to learn that rather than conducting board meetings with an agenda and homeowner attendance and calling executive sessions, the board regularly makes decisions via email — not an Internet conference, but simply emails. The manager initiates emails to all board directors with an issue or question and requests a majority decision. As soon as she obtains one, she acts on it. It's unclear whether all directors even read all the emails.

These are not emergency issues requiring immediate decisions, they are regular discussions that should take place in front of the owners at an open meeting. The excuse is that directors have busy schedules and it's not practicable to meet physically for every decision. This has been the standard operating procedure for a very long time.

Doesn't this violate some kind of law?

Answer: Your owners need to band together and take a firm stand that actions such as these will not be tolerated.

Nothing in the Davis-Stirling Act or the Corporations Code allows boards to meet and reach decisions via email. The board's actions violate the Common Interest Development Open Meeting Act, Civil Code Section 1363.05.

Challenging this board's conduct should begin by requesting the minutes of all the meetings for at least the last year, and all the other documents required to be produced by the association pursuant to Civil Code Section 1365.2(a). If the board cannot produce association minutes because it doesn't keep them, it may mean that all those decisions are without authority and invalid. Also, request copies of all the emails.

As for the excuse about the impracticality of physically meeting, board directors who don't have time to meet also don't have time to serve on the board and should be removed by the homeowners.

Association management is vested in the board of directors, not a manager. The general rules regarding meetings of the board of directors of a common-interest development are contained in Civil Code Section 1363.05. California's Corporations Code requires that notice be given for each meeting of the board of directors at least four days in advance. Conducting meetings by email violates both codes, leaving the association open to potential liability.

This is not the way any association should be operating. Steps can and should be taken to remove this board, whether by titleholder vote or lawsuit. Allowing this to continue only opens the door to trouble for everyone who owns property there.

The late Stephen Glassman, an attorney specializing in corporate and business law, co-wrote this column. Vanitzian is an arbitrator and mediator. Send questions to P.O. Box 10490, Marina del Rey, CA 90295 or noexit@mindspring.com.

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In Brazil's cracolandias , roving hordes of lost souls

SAO PAULO, Brazil — Between the high-rises in the dark center of this megacity, a swarm of people covers an entire block. They are in constant, aimless motion, glazed eyes and dirty faces illuminated repeatedly by small flashes of fire.

This is cracolandia, or crack land, and the horde is one of many moving settlements of homeless drug addicts that dominate this part of town. Hundreds, perhaps thousands, live here, sleeping and sometimes dying on the streets as other Paulistanos, residents of the fast-moving and gritty city, step past and over them on the way to work or Christmas shopping.

The men beg, hustle or recycle trash, while many of the women sell their bodies. Some shelters are available, but many of the addicts prefer not to go. Police might claim a nearby corner, then stand by and watch without making arrests.

"I had always heard about cracolandia, that you could always get high there, you could live your life and get whatever you wanted," says Tiago Bussulom Moraes, 23, who gave up on treating his addiction two years ago and took a bus here from his nearby hometown of Campinas.

"I could go back to treatment, or home, but I'm staying here," he says. "Crack, it takes hold of you. It makes you do things you don't want to do. And I regret it. But this is the life I've chosen."

Brazil is dealing with what officials call a crack epidemic, affecting Brazilians of all ages and confounding government efforts to deal with it. Almost a year after a high-profile police effort to clean up Sao Paulo's cracolandia as part of a revitalization program for the historic center, the outposts remain, but in a number of shifting locations rather than one large one.

"I've seen no improvements and some things are getting worse," said William Damiao Quirino, who has been working as a doorman and security guard downtown for six years. "Trying to clean up this or that corner isn't working. The only thing I think can work is a concerted community effort, involving residents too, to try to get these people treatment."

Crack is cheap and readily available in Brazil, as is cocaine, the drug from which it is made. Compared with other parts of the world, homeless addicts here can meet their basic needs relatively easily. Some restaurants provide food and water. There is community. And it's rarely so cold that sleeping outside is intolerable.

As crack has taken hold in Brazil over the last decade, cracolandias have popped up all around the country, from the Amazon jungle in the distant northwest to nearby Rio de Janeiro.

The best estimates are that there were about 1.5 million crack users in Brazil in 2005 and many more now.

Like cocaine and marijuana, crack is illegal in Brazil, but authorities are dealing with it more as a public health crisis than a criminal matter. Health specialists look to treatment techniques developed abroad, including in the United States, but have also learned that a "war on drugs" approach can be expensive and ineffective, said Telmo Ronzani, a specialist in drugs and public health at the Federal University of Juiz de Fora.

In 2011, President Dilma Rousseff announced a $1.9-billion plan to battle crack, largely through expanded treatment and education. The local government in Rio de Janeiro has forced underage users into treatment, and some drug traffickers there even halted crack sales, claiming to be concerned about the effect on the community. But addicted children and adults remain on the streets.

"This is a serious and difficult public problem, and could never be solved quickly. At best, it can be attacked in the medium and long term," Ronzani said. "But if we actually want the situation to improve, authorities need to enact an immediate and effective public solution that involves expanding availability to treatment and improving it."

Free treatment does exist. Adelson Pereira, 48, spends most of his nights in a public shelter a few miles from the city center that offers Narcotics Anonymous-type treatment. But tonight he is in cracolandia, going through trash looking for cans to sell, his eyes yellow and bulging.

"I made a mistake," he says sadly, referring to his decision to ditch the shelter for a few days and slip back into drugs. "It's good there, there's food, there's a bed, there's classes, and you can't use drugs inside. But it's 2,500 men, and a lot of people don't want to spend time in a place like that."

He worked as a welder and took his first hit of crack eight years ago, he says. "I passed out. It was too much. And after that" — he pronounces his words slowly — "it started to dominate me." He no longer speaks to his ex-wife but sometimes gets to see his daughters, ages 5 and 7, no younger than some residents of cracolandia.

"I've seen 6-year-olds, 8-year-olds, many of whom are forced to beg by their parents, and then there are the runaway teens that may have been beaten at home," he says.

The life is ugly, and cheap. A rock of crack, which can weigh about a quarter of a gram, costs less than $2.50; a prostitute can be had for as little as $5.

Though cracolandia has some of the city's most beautiful architecture, and sits alongside up-and-coming neighborhoods downtown, the persistence of a community of addicts, as well as access to relatively valuable trash, keeps the area attractive to the homeless.

Police have started arriving at certain corners from time to time, shifting the groups around, but life goes on largely as usual.

"When I see a 15-year-old girl, pregnant, and smoking crack, as a doctor I just can't say that's OK," said Dr. Arthur Guerra at the University of Sao Paulo. "In that kind of case, implementing involuntary internment might be the best option … but the population shouldn't expect magical solutions from the government. This also has to involve the city, families, NGOs, schools and companies. And we need prevention and education programs for the long term."

Locals live in tense harmony with the homeless, as the area fills up during the business day and then empties out to grim scenes at night. Feet from where Pereira rifles for cans, commuters coming out of the subway station step around a barefoot man on his knees, hands outstretched, wailing in despair.

"It's horrible. It's really difficult, because we see these people going through this and there's nothing we can do," says Dalva Assis, who runs a construction and electricity company downtown and spends her days walking between work sites. "They've taken over a plaza in front of one of my projects, and so I'm waiting to hear back on a request we've filed for the police to set up a base there."

Moraes says a friend who moved here with him was killed for robbing the wrong people in an attempt to get a fix. He agrees that if treatment were better, more people might accept it.

"But you're never going to solve the problem of those of us who want to keep using drugs. Crack is too powerful," Moraes says.

"What they should do is take us and just put us all in one area and let us be, so the population doesn't have to watch us using. People shouldn't have to see us living like this."

Bevins is a special correspondent.

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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.

Read More..

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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Prime Minister Mario Monti of Italy steps down

LONDON — Prime Minister Mario Monti, the technocrat who guided Italy through economic turbulence for 13 months after scandal-plagued Silvio Berlusconi left office, resigned Friday to make way for new elections.

Monti, a former economics professor and European Union commissioner, was appointed to the office, with a Cabinet of academics and economists and broad support to bring the country back from the brink of financial disaster.

"A year ago this government was launched, and today — not because of a Maya prophecy — we must bring it to an end," Monti quipped as he spoke to colleagues at an annual reception.

His resignation was provoked in part by Berlusconi's announcements this month that he was withdrawing his center-right Freedom Party's support for Monti's budget reforms and would return to the political arena, leading the party into elections.

Berlusconi's attempt to regain the prime minister's post comes despite his conviction in a corruption case and his ongoing trial on charges of paying for sex with a 17-year-old girl.

Monti's resignation followed Parliament's final approval of the last of his budgetary measures. He and his Cabinet will remain in power as caretakers until the elections, expected in mid-February.

The short run-up to the elections is fraught with questions. Monti, now a senator for life, could seek an active role in the coming government, though he has said that he has no such ambition.

He has not shown his hand yet but recently met with a new group of centrist and pro-European parties. However, such an alliance is expected to command no more than about 15% of an electorate fast losing faith in Monti's austerity cuts, seeing only Italy's rising unemployment and lack of growth.

He is expected to announce his decision Sunday.

The probable favorite in the upcoming election is a left-wing coalition under former communist politician Pier Luigi Bersani, leader of the Democratic Party, who is not opposed to Monti's reforms but must answer to powerful labor unions. According to recent polls, Bersani's coalition could attract support from about 30% of the voters.

The dwindling but still strong center-right vote is largely divided between the maverick anti-austerity Five Star Alliance movement led by TV comedian Beppe Grillo and Berlusconi's Freedom Party.

In a meeting with ambassadors Friday morning, Monti said that he thought Italy's standing had improved both economically and internationally in the last year and that he saw "an increase in Italy's authority and credibility on the international scene."

Stobart is a news assistant in The Times' London bureau.

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TSX ends flat as RIM buckles, gold miners bounce

TORONTO (Reuters) – Canada‘s main stock index ended little changed on Friday as gold miners gained on safe-haven buying amid U.S. budget uncertainty, while BlackBerry maker Research In Motion Ltd plunged more than 20 percent.

The index’s materials sector, which includes miners, rose 0.4 percent. Even though the price of gold was near its lowest level in four months, the gold-mining sub-sector added 0.9 percent as investors fretted over stalled U.S. budget talks that could throw Canada’s largest trading partner back into recession.

“As our tiptoes are over the (U.S.) fiscal cliff and we’re looking over the abyss, the markets are upset obviously, and this is sort of putting a damper on the stocks,” said John Ing, president of Maison Placements Canada.

“But we’ve had a mixed reaction in Canada, mainly because the resources have been much better, like gold for example, which is hedging into the uncertainty (around the budget talks),” he said, noting gold miners had been under pressure for the last two weeks.

Miner Barrick Gold Corp edged up 0.2 percent to C$ 33.29. Centerra Gold Inc jumped more than 3 percent to C$ 9.10.

Gold miners are playing catch-up after underperforming throughout the year and could rise further in 2013, said Gavin Graham, president at Graham Investment Strategy.

Shares of RIM dropped 22.2 percent to C$ 10.86 on fears that a new fee structure for its high-margin services segment could put pressure on the business that has set the company apart from its competitors.

The Toronto Stock Exchange‘s S&P/TSX composite index <.gsptse> fell 3.01 points, or 0.02 percent, to end at 12,385.70. It gained 0.7 percent for the week.</.gsptse>

Efforts to avoid the looming U.S. “fiscal cliff” were thrown into disarray on Friday with finger-pointing lawmakers fleeing Washington for Christmas vacations even as the year-end deadline for action edged ever closer.

Graham said that until a deal is reached in the U.S. budget talks, investors will avoid economically sensitive Canadian stocks and those most closely tied to the U.S. economy: auto parts manufacturers, forestry companies and resource stocks generally.

“The resource sectors in Canada, which is half of the index, is going to be adversely affected, correctly or not,” he said.

“Chinese demand is likely to pick up somewhat now with the new leadership there but people will be focused on the U.S. given that it is still by far the most important export market for Canada.”

($ 1=$ 0.99 Canadian)

(Additional reporting by Claire Sibonney, Julie Gordon and Jeffrey Hodgson; Editing by Peter Galloway)

Gadgets News Headlines – Yahoo! News

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