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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Russian Prosecutor Seeks Acquittal in Magnitsky’s Death

MOSCOW — A prosecutor unexpectedly pressed Monday for the acquittal of the only official to be tried in the case of Sergei L. Magnitsky, a lawyer whose death in prison three years ago generated an international furor over Russian human rights abuses.

The prosecutor’s turnabout, made in his closing argument, came as the Russian government has been moving aggressively to retaliate against the United States for adopting a law named for Mr. Magnitsky that will deny travel and investment access to Russian citizens accused of violating human rights.

Mr. Magnitsky was representing a London investment firm, Hermitage Capital, when he was arrested in November 2008 as he tried to expose a huge government tax fraud. He died, still in detention, nearly a year later. His supporters — including the firm’s founder, William F. Browder, once among the most prominent foreign investors in Russia and now a sharp critic of the Russian government — blamed the authorities for his death, saying he was denied proper medical care.

An investigation yielded charges against two people, both doctors: Larisa Litvinova, who oversaw Mr. Magnitsky’s treatment during his last weeks, and Dmitri Kratov, formerly the chief medical official of the prison where he was held for the last four months of his life, Butyrskaya. This year, prosecutors dropped a charge of professional negligence against Dr. Litvinova, saying the statute of limitations had run out.

On Monday, the prosecutor, Konstantin Bokov, urged the court to acquit Dr. Kratov. “There is no cause-and-effect relationship between Kratov’s actions and Magnitsky’s death,” Mr. Bokov said, according to Russian news services. “I request his acquittal.” A verdict is expected by the end of the week.

A lawyer for Mr. Magnitsky’s family, however, told the court that Dr. Kratov signed prison records declaring Mr. Magnitsky fit to remain imprisoned despite his repeated complaints about needing medical care, and that Dr. Kratov knew that Mr. Magnitsky was suffering from acute pancreatitis and gallstones in the days before his death.

The lawyer, Nikolay Gorokhov, blamed President Vladmir V. Putin for the prosecution’s move, noting that Mr. Putin at his annual news conference last week angrily brushed off a question about why Russian officials had not thoroughly investigated Mr. Magnitsky’s death. Mr. Gorokhov accused the authorities of failing to carry out a thorough investigation or a fair trial, and said important evidence and witnesses were suppressed.

After President Obama signed the Magnitsky Act this month, Russian officials proposed blocking American adoptions of Russian orphans and imposing sanctions on American judges and others who fail to halt or punish abuse of Russian adoptees.

Mr. Putin was pressed about the adoption ban eight times at his news conference. He would not say if he would sign the ban, but he said that Russia had to retaliate and that it was hypocritical of the United States, accused of abuses around the world, to criticize Russia on human rights.

“I don’t know the details, but I know anyway that Mr. Magnitsky died not from torture — nobody tortured him — but from a heart attack,” Mr. Putin said, adding that the only question was if he was given help in time.

But he quickly moved on to attacking the United States. “Do you think people don’t die in American prisons?” he asked. “Come on. And so what? Shall we play it up?”

Mr. Putin also pointed a finger at Mr. Browder, of Hermitage Capital, who was barred from Russia without warning in 2005, for making a mission of seeking justice in Mr. Magnitsky’s case.

“Besides, this Mr. Magnitsky, as is known, was not some human rights champion; he did not struggle for human rights,” Mr. Putin said. “He was the lawyer of Mr. Browder, who is suspected by our law enforcement of committing economic crimes.”

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Find room for God in fast-paced world, pope says on Christmas eve

VATICAN CITY (Reuters) – Pope Benedict, leading the world’s Roman Catholics into Christmas, on Monday urged people to find room for God in their fast-paced lives filled with the latest technological gadgets.

The 85-year-old pope, marking the eighth Christmas season of his pontificate, celebrated a solemn Christmas Eve mass in St Peter’s Basilica, during which he appealed for a solution to the Arab-Israeli conflict and an end to the civil war in Syria.

At the mass for some 10,000 people in the basilica and broadcast to millions of others on television, the pope wove his homily around the theme of God’s place in today’s modern world.

“Do we have time and space for him? Do we not actually turn away God himself? We begin to do so when we have no time for him,” said the pope, wearing gold and white vestments.

“The faster we can move, the more efficient our time-saving appliances become, the less time we have. And God? The question of God never seems urgent. Our time is already completely full,” he said.

The leader of the world’s some 1.2 billion Roman Catholics said societies had reached the point where many people’s thinking processes did not leave any room even for the existence of God.

“Even if he seems to knock at the door of our thinking, he has to be explained away. If thinking is to be taken seriously, it must be structured in such a way that the ‘God hypothesis’ becomes superfluous,” he said.

“There is no room for him. Not even in our feelings and desires is there any room for him. We want ourselves. We want what we can seize hold of, we want happiness that is within our reach, we want our plans and purposes to succeed. We are so ‘full’ of ourselves that there is no room left for God.”

PEACE CANDLE

Bells inside and outside the basilica chimed when the pope said “Glory to God in the Highest,” the words the gospels say the angels sang at the moment of Jesus’ birth.

Earlier on Monday the pope appeared at the window of his apartments in the apostolic palace and lit a peace candle, as a larger-than-life nativity scene was unveiled in St Peter’s Square below.

Reflecting on the gospel account of Jesus born in a stable because there was no room for Mary and Joseph in the inn, he said when people find no room for God in their lives, they will soon find no room for others.

“Let us ask the Lord that we may become vigilant for his presence, that we may hear how softly yet insistently he knocks at the door of our being and willing.

“Let us ask that we may make room for him within ourselves, that we may recognise him also in those through whom he speaks to us: children, the suffering, the abandoned, those who are excluded and the poor of this world,” he said.

He asked for prayers for the people who “live and suffer” in the Holy Land today.

The pope called for peace among Israelis and Palestinians and for the people of Syria, Lebanon and Iraq and prayed that “Christians in those lands where our faith was born may be able to continue living there, that Christians and Muslims may build up their countries side-by-side in God’s peace.”

The Vatican is concerned about the exodus from the Middle East of Christians, many of whom leave because they fear for their safety. Christians now comprise five percent of the population of the region, down from 20 percent a century ago.

According to some estimates, the current population of 12 million Christians in the Middle East could halve by 2020 if security and birth rates continue to decline.

At noon (1100 GMT/6 AM ET) the pope will deliver his twice-yearly “Urbi et Orbi” (to the city and the world) blessing and message from the central balcony of St Peter’s Basilica.

(Reporting By Philip Pullella; Editing by Myra MacDonald)

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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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Gifts That Keep Giving (if Not Exploding)

Gregory Tobias/Chemical Heritage Foundation Collections

A Chemcraft set from the mid-1950s. More Photos »

Ask scientists of a certain age about their childhood memories, and odds are they’ll start yarning about the stink bombs and gunpowder they concocted with their chemistry sets. Dangerous? Yes, but fun.

“Admittedly, I have blown some things up in my time,” said William L. Whittaker, 64, a robotics professor at Carnegie Mellon University who unearthed his first chemistry set, an A. C. Gilbert, in a junkyard around age 8. By 16, he was dabbling in advanced explosives. “There’s no question that I burned some skin off my face,” he recalled.

Under today’s Christmas tree, girls and boys will unwrap science toys of a very different ilk: slime-making kits and perfume labs, vials of a fluff-making polymer called Insta-Snow, “no-chem” chemistry sets (chemical free!), plus a dazzling array of modern telescopes, microscopes and D.I.Y. volcanoes. Nothing in these gifts will set the curtains on fire.

“Basically, you have to be able to eat everything in the science kit,” said Jim Becker, president of SmartLab Toys, who recalled learning the names of chemicals from his childhood chemistry set, which contained substances that have long since been banned from toys.

Some scientists lament the passing of the trial-and-error days that inspired so many careers. “Science kits are a lot less open-ended these days,” said Kimberly Gerson, a science blogger who lives outside Toronto. “Everything is packaged. It’s either ‘yes’ or ‘no.’ If you don’t get the right result, you’ve done it wrong and you’re out of chemicals.”

Others, though, say the new crop of science toys — even with their cartoonish packaging and heavy emphasis on neon goo — actually represent progress. More entertaining, educational and accessible than earlier products, which relied heavily on a child’s inner motivation, these toys may actually help democratize the learning of science and introduce children to scientific methods and concepts at an earlier age.

“I grew up in the 1960s, and a lot of the chemistry sets were kind of boring,” said William Gurstelle, a science and technology writer. “You’d go through the book, and at the end of the experiment you’d get some light precipitate at the bottom of the beaker. Maybe at most it changes color or something.”

Mr. Gurstelle’s books, which include “Whoosh Boom Splat” and “Backyard Ballistics,” teach people how to make dangerous projectiles, like a potato cannon that uses hair spray as launching fluid. But he had high praise for commercial science kits, which show children (among other things) how to make slime.

Jeff Swensen for The New York Times

William L. Whittaker at the Planetary Robotics Lab at Carnegie Mellon University surrounded by the robots he has created.

“Well, that’s a pretty cool thing to have when you’re done,” Mr. Gurstelle said. “You’re not going to really learn to be a chemist from a chemistry set when you’re in seventh grade; you’re just going to be inspired. The point is that new chemistry sets and new toys are just better, because the manufacturers have figured out how to make them more fun.”

Some toy makers, like SmartLab, Mr. Becker’s company, have used this philosophy to give classic toys a makeover. One of SmartLab’s takes on a chemistry set, for instance, is the Extreme Secret Formula Lab, which comes with “squishy-lidded bubble test tubes” and “an abundance of glow-in-the-dark powder.” The game of Mousetrap has been re-envisioned as the Weird and Wacky Contraption Lab, meant to bring out children’s Rube Goldberg talents. And the slot car tracks that Mr. Becker recalls snapping together in his youth have been translated into a robot called ReCon 6.0, which children can program to roam around.

Mike Kane for The New York Times

Jim Becker of SmartLab Toys.

“What we do is give kids the opportunity to learn through problem solving,” Mr. Becker said.

Of course, technology has also remade the experience of learning science. Children may be more likely to click on a science app than to go play outside.

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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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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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Newtown Mourns Last of Its Children Killed in Massacre

NEWTOWN, Conn. — This community laid to rest on Saturday the last of the children killed in a schoolhouse massacre.

In a town devastated by violence, besieged by worldwide attention from the news media and struggling to move forward, the burial of Josephine Grace Gay, 7, brought to an end a bleak procession of funerals that began not long after Adam Lanza killed 20 children and 6 staff members at Sandy Hook Elementary School.

“This has been a challenge for us,” Msgr. Robert E. Weiss said during his homily at Josephine’s funeral Mass at St. Rose of Lima Roman Catholic Church.

Funeral after funeral, wake after wake, he said, it had been faith, family and friendship that held the community together.

He recalled the terrible hours after the shooting stopped on Dec. 14, when he waited with families at the firehouse near the school, with parents clinging to the hope that their children had made it out unharmed.

At 3 p.m. that day, he said, Josephine’s parents were told that she had not survived.

“It does not make sense,” Monsignor Weiss said, adding that the children did not die in vain. “If these 20 cannot change the world, then no one can,” he said.

He added that it was now up to everyone to bring out the best in themselves and one another.

“You should be angry,” Monsignor Weiss said. “But don’t hold onto it.”

The shootings have resonated around the world, and have set off an intense national discussion on gun control, mental health and other issues.

That discussion continues, yet the focus here Saturday was not on questions of policy or new laws. It was on a first grader known to family and friends as Joey, who had turned 7 days before she was killed.

Her father, Bob Gay, noted that though she had autism and was unable to speak, “you don’t need words to say, ‘I love you.’ ”

Mr. Gay and Josephine’s mother, Michele Gay, shared with the congregation some of the “life lessons” they learned from their daughter.

“You can’t really appreciate a movie until you have watched it 300 times,” Ms. Gay said, before mentioning another lesson: “iPhones are not waterproof.”

Josephine’s father said that she had taught him not to “sweat the small stuff; it’s all small stuff.” And this: “Even the smallest of us can do great things.”

In a town that was plunged into unimaginable shock and sorrow a little more than a week before, there seemed to be a determination at the funeral to be upbeat. Many people wore purple, Josephine’s favorite color.

There were two other funerals for children killed at Sandy Hook on Saturday, both held outside of Newtown.

Ana Marquez-Greene, 6, was mourned at a private ceremony in Bloomfield, Conn. She was the daughter of the jazz saxophonist Jimmy Greene, who posted a short tribute to his daughter on his Facebook page.

“As much as she is needed here and missed by her mother, her brother and me, Ana beat us all to paradise,” he wrote the day after the shootings. “I love you, sweetie girl.”

Her mother, Nelba Marquez-Greene, in a statement, recalled her budding musical talent.

“In a musical family, her gift for melody, pitch and rhythm stood out remarkably,” she said.

In Ogden, Utah, Robbie and Alyssa Parker buried their 6-year-old daughter, Emilie.

Mr. Parker was one of the first parents of a child killed at the school to speak out publicly, at an emotional news conference one week ago.

Choking back tears, he vowed not to let what happened “turn into something that defines us, but something that inspires us to be better, to be more compassionate and more humble people.”

Those sentiments were echoed in the notes and posters left at memorials across Newtown.

The piles of stuffed animals and flowers and toys have grown each day, but there was a hope that with the final funeral, the people here could begin to grieve outside of the constant glare of media attention.

Gov. Dannel P. Malloy, who had ordered all flags in the state to be flown at half-staff after the massacre, said it was time to raise them once again.

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