Bengals clinch playoff spot, edge Steelers 13-10

PITTSBURGH (AP) — Andy Dalton and A.J. Green have the Cincinnati Bengals back in the postseason.

Dalton hit Green for a 21-yard pass in the final moments, setting up Josh Brown's 43-yard field goal with 4 seconds remaining. That lifted the Bengals over the Pittsburgh Steelers 13-10 on Sunday, sending Cincinnati into the playoffs for a second straight season.

It's the first time since 1981-82 that Cincinnati made the playoffs in consecutive years — and the first time not involving a strike season.

Brown missed a 56-yarder earlier in the quarter. He earned a second chance when Reggie Nelson picked off Ben Roethlisberger and returned it to the Pittsburgh 46 with 14 seconds remaining. Andy Dalton found Green down the right sideline, setting up Brown's winner.

Dalton completed 24 of 41 for 278 yards and two interceptions for the Bengals (9-6), who snapped a five-game losing streak to Pittsburgh (7-8). Green caught 10 passes for 116 yards for Cincinnati.

Roethlisberger completed 14 of 28 passes for 220 yards with a touchdown and two interceptions, including his costly mistake in the final seconds that ended Pittsburgh's playoff hopes. It marked the second straight week a Roethlisberger pick cost the Steelers: He threw an interception on the second play of overtime in last week's loss at Dallas.

The Steelers needed to win out to play into January, but couldn't manage any momentum against a Cincinnati defense that gave Roethlisberger problems all afternoon. The Bengals sacked Roethlisberger four times and allowed Pittsburgh to complete just 2 of 14 third downs.

Cincinnati wasn't much better, managing all of 14 yards rushing against the NFL's top-ranked defense. But Dalton and Green worked just enough magic.

Pittsburgh did a decent job of keeping Dalton and Green in check, forcing a season-high three turnovers and making a season-high six sacks. But the offense couldn't take advantage.

Still, the Steelers had one last chance when they took over with 44 seconds left. Roethlisberger rolled right and tried to hit Mike Wallace down the sideline. The ball sailed over Wallace's head and into the arms of Nelson, who had dropped an earlier pick.

It was just enough time for Dalton and Green to get together one last time and help Cincinnati take one more step away from its mediocre past.

The Steelers, meanwhile, head into next week's season finale trying to avoid their first losing season under coach Mike Tomlin after falling for the fifth time in six games.

Both teams squandered opportunities earlier in the fourth quarter.

The Bengals drove into Pittsburgh territory before stalling at the Steelers 38. Cincinnati coach Marvin Lewis sent out Brown to attempt a 56-yard field goal into the tricky Heinz Field winds.

The kick was never close, giving the Steelers premium field position with 3:18 left.

Pittsburgh, however, had its own kicking issues. The Steelers moved to the Cincinnati 36, then brought out Shaun Suisham for a 53-yard attempt that was short all the way.

The Steelers spent the week insisting they play their best when backed into a corner, then spent most of the first half getting pushed around by the Bengals. Roethlisberger, who had been critical of offensive coordinator Todd Haley after the loss to Dallas, struggled getting into a rhythm.

The quarterback had voiced concern over the inability to get the ball to tight end Heath Miller against the Cowboys and tried to make up for it early. Cincinnati was waiting.

Leon Hall stepped in front of a crossing pass to Miller late in the first quarter and sprinted 17 yards for a touchdown to give the Bengals the lead. Pittsburgh, fueled by the return of running back Rashard Mendenhall following a one-game suspension for conduct detrimental to the team, drove deep into Cincinnati territory only to have Suisham shank a 24-yard field goal wide left following a botched snap.

The Bengals eventually went up 10-0 on a 41-yard field goal by Brown late in the second quarter before the Steelers finally found some life. Brown streaked down the sideline for a 60-yard touchdown catch to pull Pittsburgh within 10-7.

___

Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL

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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..

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..

Is the Christmas card dead?

Author Nina Burleigh says the holiday photo is dead — and the internet killed it

Every year around the holidays, countless Americans sit down at their dining room tables to thoughtfully scribble pen-and-paper updates about how they are and what they’ve been doing with their lives to a select number of friends. These messages are usually written on the back of a recent family photograph (sometimes with Santa hats), before they’re sealed, stamped, and mailed around the country, where they’re displayed like a trophy over someone else’s fireplace.

Could that all be changing? This year, especially, there seems to be a dearth of dead-tree holiday cheer filling up mailboxes across the country. In a recent column for TIME, author Nina Burleigh says the spirit once distilled inside the Christmas card is dying, and a familiar, if fairly obvious perpetrator killed it: The internet. “There’s little point to writing a Christmas update now, with boasts about grades and athletic prowess, hospitalizations and holidays, and the dog’s mishaps, when we have already posted these events and so much more of our minutiae all year long,” she writes. “The urge to share has already been well sated.”

[Now] we already have real-time windows into the lives of people thousands of miles away. We already know exactly how they’ve fared in the past year, much more than could possibly be conveyed by any single Christmas card. If a child or grandchild has been born to a former colleague or high school chum living across the continent, not only did I see it within hours on Shutterfly or Instagram or Facebook, I might have seen him or her take his or her first steps on YouTube. If a job was gotten or lost, a marriage made or ended, we have already witnessed the woe and joy of it on Facebook, email and Twitter.

Burleigh says the demise of the Christmas card is deeply saddening. “It portends the end of the U.S. Postal Service,” she writes. “It signals the day is near when writing on paper is non-existent.” It’s true, says Tony Seifart at Memeburn — “my mantle is empty this year. In fact I haven’t received one Christmas card yet.”

SEE ALSO: The perks and perils of our newly indexed society

Let’s not get too nostalgic just yet, says Alexis Madrigal at The Atlantic. Research firm IBISWorld anticipates that purchases of cards and postage will be the highest it has been in five years — $ 3.17 billion total. And Hallmark, the industry’s biggest player, has seen revenue hold steady since the early 2000s despite the financial crisis. We could also think about this another way: That desire to share, the willingness to inform, could just be extending itself beyond the physical form of the holiday photo. 

No matter what time of the year, people now write contemplative letters with weird formatting to an ill-defined audience of “friends”; these are Christmas letters, whether Santa is coming down the chimney or not. There are reindeer horns on pugs in July. And humblebrags about promotions in April. There are dating updates in November. And you can disclose that you were voted mother of the year any damn day you please… For good or for ill, perhaps we’re seeing not the death of the holiday card and letter, but its rebirth as a rhetorical mode. Confessional, self-promotional, hokey, charming, earnest, technically honest, introspective, hopey-changey: Oh, Christmas Card, you have gone open-source and conquered us all. 

The spirit of the Christmas card is indeed alive and well. It’s just not necessarily in a Christmas card.

SEE ALSO: Poison pens and lipstick guns: 8 real-life spy weapons

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The Lede Blog: Rorschach in Hebron: Grainy Footage Fails to End Arguments Over Fatal Shooting

Video of a fatal shooting last week at a checkpoint in the West Bank city of Hebron, released by Israel’s military.

When the Israel Defense Forces released 49 seconds of grainy, black-and-white video this week, showing some of what happened at a checkpoint in the West Bank city of Hebron before the fatal shooting of a Palestinian teenager by an Israeli officer, a military spokesman expressed confidence that the security-camera footage proved that the killing was justified.

As The Lede reported last week, the officer who shot and killed Muhammad al-Salameh on his 17th birthday said that the boy had subdued her partner and pressed a real-looking toy gun to his head, leaving her no alternative but but to fire. The I.D.F. spokesman Capt. Barak Raz said that the video left no doubt that the young female officer had acted correctly.

(Cont’d) Watch security tape and ask yourself how you would react if this was your partner: https://t.co/JYHOE7Bz

— Captain Barak Raz (@CaptainBarakRaz) 17 Dec 12

Looking at the footage posted on the I.D.F.’s Arabic-language YouTube channel though, some Palestinian activists and skeptical Israeli journalists asked why the video was edited, omitting part of the encounter, and also seemed not to match the initial account of the incident provided to the Israeli media by the officer who fired the fatal shots.

Parsing the clip on the Israeli news blog +972, the journalist Noam Sheizaf observed that the video appeared to show that the boy who was killed did throw the first punch in a fistfight with an officer at the checkpoint. But, he added, that officer seemed to have broken free of the boy before any shots were fired by the second officer, identified in Israeli media accounts as N.

It is hard to tell what’s going on – Muhammad and a soldier can be seen exchanging blows, and it seems that the Palestinian is the first to try and hit the soldier (0:33). The alleged gun cannot be spotted, but the clip – which is slightly edited (0:24) – is very dark. The second soldier comes out to the street and when the soldier and the Palestinian are away from each other, she shoots Muhammad (0:48). Unless the teen was indeed holding a gun, the soldiers don’t seem to be under threat at that moment.

The Palestinian blogger Abir Kopty argued that the video appeared to show that the fight between the young Palestinian and the officer at the checkpoint was also different in several respects to all of the accounts of the incident provided to the Israeli media by the military.

The army claims that at one point Salaymeh was pointing a gun at the soldier, in another he knocked the soldier down and pointed a gun at him, and in a third version that he placed the gun at the soldier’s temple. The video does not show any of these versions. It seems like Salaymeh was fist fighting with his hands without any gun.

Another Israeli journalist, Larry Derfner, catalogued the questions not answered by the clip:

We don’t know if Salameh pulled a realistic-looking cigarette-lighter gun during the fight, which was N.’s stated justification for shooting him; you can’t see such an object in the video, although again, the video is dark and not very distinct, as if done in “night vision.”

We don’t know what happened just before Salameh went up to a border policeman and attacked him with his fists – there’s a cut in the 54-second video at 0:24. We also don’t know why the I.D.F. waited four days before making the video available to the public.

Although no one doubts that the video was recorded during the incident, questions have been asked in the past about the Israeli military’s use of editing in footage uploaded to YouTube.

Mr. Derfner also reported that a Palestinian witness who told the Israeli rights group B’Tselem “that the border policemen saw Salameh approaching the checkpoint with a gun that looked real, and either confiscated it or tried to, and that Salameh was shouting, ‘It’s mine, it’s mine’ during the fight, and was either trying to grab the gun back from the border policeman or stop him from taking it.”

Sarit Michaeli, a spokeswoman for B’Tselem, the Israeli Information Center for Human Rights in the Occupied Territories, told The Lede in an e-mail that a witness to the incident “told us that Salameh had the gun-shaped lighter on him (not drawn). The checkpoint is near his family home. The Border Police officers discovered the gun, tried to or did indeed confiscate it, which sparked an altercation, and he managed to get it back. That’s when he was heard shouting ‘mine.’ Our witness described a fight between Salameh and the officers, in which they exchanged blows, and was then shot.”

She added:

The fight is seen in the security camera footage but the confiscation is not. The footage released is an incomplete film though, a sequence was cut out of it. I haven’t seen an official explanation of what was cut and why. It seems like a very odd decision to me, releasing edited footage is only bound to spark more controversy instead of quashing it.

Video of the tense scene at the checkpoint just after the shooting, which includes a brief glimpse of the dead boy’s body, was posted on YouTube by B’Tselem last week.

A second Palestinian witness, who arrived at the checkpoint shortly after the shooting, provided B’Tselem with photographs of the young man’s body and the toy gun. The boy’s father told reporters from the Israeli newspaper Haaretz that he had never seen the toy gun before but it might have been given to his son that day as a birthday present.

---

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Temple upsets No. 3 Syracuse 83-79

NEW YORK (AP) — Khalif Wyatt had never been in Madison Square Garden let alone played there.

The Philadelphia native left the building on Saturday after scoring a career-high 33 points and being the key to Temple beating No. 3 Syracuse 83-79 in the first Chevrolet Gotham Classic.

"I always wanted to play here because all the great players had a chance to play here," the 6-foot-4 senior said. "This was a chance for us to show everyone that Temple is a real program."

Anthony Lee had a career-high 21 points for the Owls (9-2), who were coming off a 10-point home loss to Canisius.

"I don't think we would have won today without the loss in the last game," Temple coach Fran Dunphy said. "Our guys did a great job today. I wish it was worth more than one victory."

This is the fifth straight season Temple has beaten a top 10 team while being unranked.

The latest win in that stretch game with the combination of Wyatt from the outside and Lee inside.

"We wanted to go inside and out and that meant me going up strong and fighting for rebounds," said Lee, who had nine rebounds, five offensive, and worked the baseline again and again against Syracuse's vaunted zone. "That's playing the Temple game."

Dunphy said Wyatt challenged himself after a poor game against Canisius.

"He made some really good plays when we were struggling to score and had to stay in the game," Dunphy said.

The Orange led by two at halftime but never took a lead in the second half even though there were four ties, the last at 59-59 with 10:23 to play.

C.J. Fair had a career-high 25 points for Syracuse (10-1), which had its 52-game regular-season nonconference winning streak snapped. Jim Boeheim remained at 900 wins, two behind Bob Knight for second place all-time among Division I men's coaches. Duke's Mike Krzyzewski has 938 wins.

Wyatt made all 15 of his free throw attempts and Lee was 11 of 14 as the Owls were 29 of 36 overall.

Syracuse was 19 of 34 from the line including missing four in the final 6 minutes when it was mostly a one-possession game and point guard Michael Carter-Williams finished 7 of 15.

"They made free throws, we didn't," Boeheim said. "You don't like to say it comes down to that, but when you miss 15 free throws it's tough to win any game."

Carter-Williams took the heat.

"If I make free throws we win the game," he said.

Temple hit three 3-pointers in an 11-3 run that gave it the lead for good. Scootie Randall started the run with a 3 that broke the 59-all tie. He closed the run with another 3, his only points of the game.

The 3-point line also hurt the Orange, who were 2 of 12 from behind the arc while Temple was 8 of 24.

"It was one of those nights when it wouldn't fall," said Fair, whose only 3-point attempt of the game brought the Orange within 74-72 with 3:01 left but the Owls went 11 of 15 from the free throw line over the final 2:30.

Temple's last field goal was an offensive rebound by Quenton DeCosey with 5:41 left that gave the Owls a 72-66 lead.

Rahlir Hollis-Jefferson had four points and 10 rebounds for the Owls.

Brandon Triche had 17 points for Syracuse. Baye Moussa Keita added 12 and Carter-Williams, who leads the nation in assists at 10.7 per game, had 13 points and six assists.

"Wyatt was able to create a lot of contact and that got him to the free throw line," Carter-Williams said. "They didn't play off me and I have to get used to that. We have to learn from this. It's a long season."

Temple missed 10 of its first 12 shots in falling behind 19-10. The Owls, behind Wyatt who had 20 points in the first half, started hitting shots against the Orange's zone defense and they made nine of their next 14 shots and tied the game at 35. Syracuse scored five straight points but Wyatt capped his big half with a 3-pointer with 17 seconds left and Temple was within 40-38 at halftime.

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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..

News Analysis: Has Lego Sold Out?

FOR generations of American children and their parents, Legos were the ultimate do-it-yourself plaything. Little plastic bricks, with scant instructions, just add imagination.

In a wired world, they would now seem the ultimate anachronism, the only click being the sound of blocks snapping together. This holiday season, though, Lego is again among the hottest brands, and not just for the blocks, but a raft of Lego-related video games, children’s books and a TV spinoff — many of which are hugely popular in their categories.

In leading this revival of Lego, and creating a multimedia juggernaut, executives have shown great imagination. But some parents and researchers worry that the company’s gain has come at a cost to its tiny consumers: diminishing the demand for their imagination, the very element that made the Lego brand famous in the first place.

Even when actual bricks are involved, today’s construction sets are often tied to billion-dollar franchises like “Star Wars” and “Lord of the Rings” — and the story lines therein — and invite users to follow detailed directions, not construct their own creations from whole brick. It’s less open-ended, some parents and researchers say, and more like paint-by-numbers.

“When I was a kid, you got a big box of bricks and that was it,” said Tracy Bagatelle-Black, 45, a public relations consultant in Santa Clarita, Calif., north of Los Angeles. “What stinks about Lego sets now is that they’re not imaginative at all.”

Not that she can resist the hue and cry from her children. For Hanukkah, Molly, her 11-year-old daughter, got two Lego products, neither of them blocks; her son, Alex, 5, got even more, including a Lego Darth Vader Clock, a Lego board game, a Lego sticker book — at the top of his list — and a Lego “Ninjago” video game.

Oh, yes, and he also got some traditional Legos, sort of: a Lego Super Hero Captain America and Lego Marvel Super Heroes set, both of which come with detailed instructions.

For their part, officials at Lego — a privately held, Denmark-based company — say their efforts in books, television and video games are still creatively minded and aimed at driving kids “back to the playroom.”

According the company’s research, parents “don’t mind the video games, they don’t mind the books, they don’t mind the TV series because it’s intensifying their child’s desire to build,” said Michael McNally, the director of brand relations for Lego’s American operations, based in Enfield, Conn. “And they love watching their kids build.”

And so does the Lego Group, which nearly melted down financially in the middle of the last decade, with layoffs and huge losses. The company has since turned things around, reporting a 17 percent increase in revenue in 2011, with product lines based on “Pirates of the Caribbean” and “Harry Potter” performing “considerably above expectations.”

“Lego Batman 2: DC Super Heroes,” for instance, was the No. 1 video game in June, selling 450,000 copies in the United States alone, according to NPD, a market research firm. (Collectively, Lego brand games have been among the top five best-selling game franchises in each of the last five years, according to NPD.)

Then there is Ninjago, with Lego figures as martial arts masters, which was the biggest launch in company history. The animated “Ninjago: Masters of Spinjitzu” series on the Cartoon Network ranked as one of the top cable shows in America last year among boys ages 2 to 11, according to the Nielsen Company, going toe to toe with the likes of SpongeBob SquarePants (which also has a Lego version).

Of course, lots of toy companies have gone the multimedia route (see: Barbie). But for parents and some researchers, there’s a narrative twist with Lego, which engenders such good will from parents because of its education-centric reputation. It was, literally and proverbially, a building block.

“Parents are confusing the brand with the product and, more important, what it delivers” said Dimitri Christakis, director of the Center for Child Health, Behavior and Development at the University of Washington, whose research focuses on the impact of interaction with various media on children’s brains. Regarding the evolution from open-ended toys to multimedia and bricks with specific building plans, he added: “Depending on how far it goes, it could wind up, quite frankly, as the opposite of blocks.”

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Obama Nominates Kerry for Secretary of State

WASHINGTON — President Obama on Friday nominated Senator John Kerry of Massachusetts as secretary of state, choosing an elder of the Democratic Party’s foreign policy establishment and a crucial political ally in the Senate to succeed Hillary Rodham Clinton.

“In a sense, John’s entire life has prepared him for this role,” Mr. Obama said, making the widely expected announcement at the White House. “He’s not going to need a lot of on-the-job training.”

With Mr. Kerry standing at his side, the president praised Mr. Kerry’s combat service in the Vietnam War and his three decades in the Senate, which Mr. Obama said had placed him at the heart of “every major foreign policy debate for the past 30 years.”

Mr. Kerry, the president said, had also earned the respect of his Senate colleagues and he expressed confidence that Mr. Kerry would be quickly confirmed. In recent weeks, Senator John McCain, the Arizona Republican, has jokingly referred to his colleague as “Mr. Secretary.”

Mr. Obama’s first choice for the job, Susan E. Rice, the ambassador to the United Nations, asked Mr. Obama to withdraw her name last week after Mr. McCain and other Republicans threatened to block her nomination because of statements she made after the lethal attack on the American mission in Benghazi, Libya.

In addition to Mr. Kerry’s foreign-policy credentials, Mr. Obama noted that he had supported the president’s political career at key moments — not least, he said, by inviting a “young Illinois state senator to address the Democratic National Convention in 2004.”

Mr. Kerry, 69, was his party’s presidential candidate in that election, losing to George W. Bush. He is chairman of the Senate Foreign Relations Committee and has carried out several diplomatic missions for the Obama administration, helping to persuade President Hamid Karzai of Afghanistan to agree to a runoff election in 2009. Early in the administration, he also tried to engage President Bashar al-Assad of Syria, who has waged a brutal crackdown on his own people as he fights to cling to power.

During the last campaign he also played the role of Mitt Romney in Mr. Obama’s debate preparations.

“Nothing brings two people closer together than two weeks of debate prep,” the president joked. “John, I’m looking forward to working with you rather than debating you.”

Mr. Kerry has long coveted the job of secretary of state.

Mrs. Clinton, who is recovering from the effects of a concussion, did not appear at the White House announcement.

“Hillary wanted very much to be here today, but she continues to recuperate,” the president said. “I had a chance to talk to her earlier today, and she is in good spirits and could not be more excited about the announcement that I’m making.”

Mr. Obama still has to fill two other key openings in his national security team, finding replacements for Secretary of Defense Leon E. Panetta, who intends to resign; and David H. Petraeus, director of the Central Intelligence Agency, who resigned in November because of an extramarital affair.

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Douglas wins AP female athlete of the year honors

When Gabby Douglas allowed herself to dream of being the Olympic champion, she imagined having a nice little dinner with family and friends to celebrate. Maybe she'd make an appearance here and there.

"I didn't think it was going to be crazy," Douglas said, laughing. "I love it. But I realized my perspective was going to have to change."

Just a bit.

The teenager has become a worldwide star since winning the Olympic all-around title in London, the first African-American gymnast to claim gymnastics' biggest prize. And now she has earned another honor. Douglas was selected The Associated Press' female athlete of the year, edging out swimmer Missy Franklin in a vote by U.S. editors and news directors that was announced Friday.

"I didn't realize how much of an impact I made," said Douglas, who turns 17 on Dec. 31. "My mom and everyone said, 'You really won't know the full impact until you're 30 or 40 years old.' But it's starting to sink in."

In a year filled with standout performances by female athletes, those of the pint-sized gymnast shined brightest. Douglas received 48 of 157 votes, seven more than Franklin, who won four gold medals and a bronze in London. Serena Williams, who won Wimbledon and the U.S. Open two years after her career was nearly derailed by a series of health problems, was third (24).

Britney Griner, who led Baylor to a 40-0 record and the NCAA title, and skier Lindsey Vonn each got 18 votes. Sprinter Allyson Felix, who won three gold medals in London, and Carli Lloyd, who scored both U.S. goals in the Americans' 2-1 victory over Japan in the gold-medal game, also received votes.

"One of the few years the women's (Athlete of the Year) choices are more compelling than the men's," said Julie Jag, sports editor of the Santa Cruz Sentinel.

Douglas is the fourth gymnast to win one of the AP's annual awards, which began in 1931, and first since Mary Lou Retton in 1984. She also finished 15th in voting for the AP sports story of the year.

Douglas wasn't even in the conversation for the Olympic title at the beginning of the year. That all changed in March when she upstaged reigning world champion and teammate Jordyn Wieber at the American Cup in New York, showing off a new vault, an ungraded uneven bars routine and a dazzling personality that would be a hit on Broadway and Madison Avenue.

She finished a close second to Wieber at the U.S. championships, then beat her two weeks later at the Olympic trials. With each competition, her confidence grew. So did that smile.

By the time the Americans got to London, Douglas had emerged as the most consistent gymnast on what was arguably the best team the U.S. has ever had.

She posted the team's highest score on all but one event in qualifying. She was the only gymnast to compete in all four events during team finals, when the Americans beat the Russians in a rout for their second Olympic title, and first since 1996. Two nights later, Douglas claimed the grandest prize of all, joining Retton, Carly Patterson and Nastia Liukin as what Bela Karolyi likes to call the "Queen of Gymnastics."

But while plenty of other athletes won gold medals in London, none captivated the public quite like Gabby.

Fans ask for hugs in addition to photographs and autographs, and people have left restaurants and cars upon spotting her. She made Barbara Walters' list of "10 Most Fascinating People," and Forbes recently named her one of its "30 Under 30." She has deals with Nike, Kellogg Co. and AT&T, and agent Sheryl Shade said Douglas has drawn interest from companies that don't traditionally partner with Olympians or athletes.

"She touched so many people of all generations, all diversities," Shade said. "It's her smile, it's her youth, it's her excitement for life. ... She transcends sport."

Douglas' story is both heartwarming and inspiring, its message applicable those young or old, male or female, active or couch potato. She was just 14 when she convinced her mother to let her leave their Virginia Beach, Va., home and move to West Des Moines, Iowa, to train with Liang Chow, Shawn Johnson's coach. Though her host parents, Travis and Missy Parton, treated Douglas as if she was their fifth daughter, Douglas was so homesick she considered quitting gymnastics.

She's also been open about her family's financial struggles, hoping she can be a role model for lower income children.

"I want people to think, 'Gabby can do it, I can do it,'" Douglas said. "Set that bar. If you're going through struggles or injuries, don't let it stop you from what you want to accomplish."

The grace she showed under pressure — both on and off the floor — added to her appeal. When some fans criticized the way she wore her hair during the Olympics, Douglas simply laughed it off.

"They can say whatever they want. We all have a voice," she said. "I'm not going to focus on it. I'm not really going to focus on the negative."

Besides, she's having far too much fun.

Her autobiography, "Grace, Gold and Glory," is No. 4 on the New York Times' young adult list. She, Wieber and Fierce Five teammates Aly Raisman and McKayla Maroney recently wrapped up a 40-city gymnastics tour. She met President Barack Obama last month with the rest of the Fierce Five, and left the White House with a souvenir.

"We got a sugar cookie that they were making for the holidays," Douglas said. "I took a picture of it."

Though her busy schedule hasn't left time to train, Douglas insists she still intends to compete through the Rio de Janeiro Olympics in 2016.

No Olympic champion has gone on to compete at the next Summer Games, but Douglas is still a relative newcomer to the elite scene — she'd done all of four international events before the Olympics — and Chow has said she hasn't come close to reaching her full potential. She keeps up with Chow through email and text messages, and plans to return to Iowa after her schedule clears up in the spring.

Of course, plenty of other athletes have said similar things and never made it back to the gym. But Douglas is determined, and she gets giddy just talking about getting a new floor routine.

"I think there's even higher bars to set," she said.

Because while being an Olympic champion may have changed her life, it hasn't changed her.

"I may be meeting cool celebrities and I'm getting amazing opportunities," she said. "But I'm still the same Gabby."

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AP Projects Editor Brooke Lansdale contributed to this report.

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