‘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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Kraft's new recipe for sales: Updating products for men, millennials

The pot pie kit comes with pouches of Velveeta cheese, biscuit topping, vegetables and seasoning. The cook sautes chicken until done, then adds milk, vegetables and seasoning, and cooks for another minute. The chicken mixture goes into a baking dish and gets topped with the cheese. Finally, the biscuit mix, to which more milk has been added, goes on the very top. The Velveeta Cheesy Casserole is ready in about 18 minutes at 425 degrees.

Then there's Oscar Mayer's pulled pork that's sold in a clear plastic tub. It's precooked, shredded and seasoned. Kraft is selling the meat without the sauce so cooks can choose their own and add as much as desired.

These and other new products are part of Kraft Foods Group's efforts to attract new customers: millennials and men. The recession disproportionately affected men, who are now doing about 40 percent of the cooking, according to the U.S. Bureau of Labor Statistics.

Northfield-based Kraft has found that both groups are cooking more and looking for flexible recipes, ways to customize their food and have fun in the kitchen. So Kraft is updating its stable of mature brands in ways that appeal to them.

Millennials, age 18 to early 30s, are beginning to cook and don't want to do things like their parents did. So Kraft is offering more products that require some effort. Just not too much effort.

A Kraft study showed younger men cooking even more than their older counterparts — 42 percent of millennial men do all the cooking in the household, while 76 percent do at least some cooking. They also like to experiment with their dishes.

"Now they'll talk about cooking like guys would talk about a hobby 20 years ago," said Barry Calpino, vice president of breakthrough innovation at Kraft. "It's an adventure, it's an experience, it's fun, they talk about 'their signature.'"

Men feel they have more latitude as cooks, according to Robin Ross, associate director of culinary at Kraft. "Women want to please their families and for everyone to like what they make,'' she said. Men, she said, tend not to feel the same pressure. "Men have more of a free hand."

Kraft Foods, a $19 billion a year packaged North American grocery business, was spun off in October from Deerfield-based Mondelez International. Kraft CEO Tony Vernon promised mid-single-digit operating income growth rates for the company, and acknowledged it needs to develop new, more modern products for its brands and increase advertising support to make customers aware of them.

While Vernon hasn't released targets for his ad budget, Kraft has lagged competitors, investing the equivalent of 3 percent of sales toward advertising and marketing, compared with 4.5 percent of sales at competitors, according to the company.

During the company's most recent earnings call, Vernon underscored double-digit sales growth for Lunchables, Velveeta, and MiO, a liquid concentrate used to flavor water, citing new products and subsequent advertising. However, he acknowledged work to do with Jell-O, to capitalize on "yogurt's explosive growth," and with Planters "to re-establish category leadership and profitable growth."

On Friday, Kraft shares closed at $45.53, up 2 percent from the Oct. 1 spinoff.

Simply being a smaller company, Calpino said, means Kraft can lavish attention on brands like Velveeta, which hadn't seen much attention in decades.

"Five or six years ago, I'm not sure we'd do innovation reviews" on Velveeta, Calpino said. "It wasn't even on the list."

Phil Lempert, a supermarket industry expert, said the millennial generation poses challenges for big food companies, which are not known for rapid change. Companies like Kraft, he said, have to "keep it fresh, keep it changing." Young people, he said, "never want to wake up and have the same meal in an entire lifetime.'' He also said that unlike their predecessors, millennials are more interested in "ethnic foods and adventure than ever before."

Lempert said a lot of millennials' tastes are "being driven by food trucks,'' serving products like tacos with a few different meats with a level of high quality and bold flavors. In turn, that has raised millennials' expectations on everything from a restaurant meal to a box of Kraft Macaroni and Cheese.

Lynn Dornblaser, director of innovation and insight at Mintel International, said the fact that Kraft offers some of its new products like easy-to-use, three-pack sauce packets should be a hit because millennials love to cook, but hate to clean.

"Cleaning is a barrier to cooking from scratch," she said. It's the same for male cooks. Even making a white sauce for pasta, Dornblaser said, "you've got dishes to wash, measuring to do, steps to follow."

So products like Kraft's new Velveeta casseroles, pulled pork, Fresh Take cheese and bread crumb mixtures and Velveeta Toppers cheese sauce pouches "offer the ability for consumer to be a little creative with what they're cooking but without too much bother," she said.

Last year, Velveeta launched Cheesy Skillets dinner kits, the brand's biggest launch in more than 20 years. It's a stark departure for a brand best known for Shells & Cheese and its ability to melt over nachos. Consumers saute beef, add cheese sauce from a pouch, cook the pasta, mix, and add hamburger toppings such as shredded lettuce and diced tomato.

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Alderman calls fire that claimed the lives of 2 children 'senseless'

A 3-year-old boy and 2-year-old girl died this morning after they and two other children were left home alone in the Englewood neighborhood, officials say. (Posted Dec. 22nd, 2012)

Hours before a fire swept through their bedroom, killing their younger sister and cousin, Darnell and Marquis were watching Batman cartoons as their mother and aunt were dressing for a night out, the boys said in an interview.

But in the middle of the night, before the two adults returned home to check on the four children, a hot plate being used to heat the room fell onto some clothes, igniting a fire, the boys and authorities said.

Darnell, 7, and Marquis, 4, managed to run out a back door with the help of their aunt to escape the fire in their West Englewood home, they said.

But a 2-year-old boy, identified at the Cook County medical examiner’s office as Javaris Meakens, and a 3-year-old girl, Jariyah Meakens, perished in the blaze that was contained in a bedroom of the house.

“When the fire started, everything shut off,” said Darnell, who said it was his sister and cousin who were left in the house. “Auntie came to get us.
“When (she) saw the fire, she called all our names. When I opened the door, she told me, ‘Come on, the fire’s getting closer.’”

On Saturday, the children’s mothers were being questioned by Chicago police, but no charges had been filed. The two surviving children told authorities they were left alone in the house when the fire broke out.

The children were interviewed as they sat with four adult women, but they did not want to use their last names. Because their parents have not been charged, police would not release the names of the children’s mothers.

The fire occurred about 3:30 a.m. in the 6400 block of South Paulina Street, officials said.

When firefighters arrived, there were flames shooting out of the middle bedroom, and smoke throughout the first floor apartment, said James Mungovan, the Deputy District Chief for District 5 with the Chicago Fire Department.

At first, firemen concentrated on getting water to the blaze, Mungovan said. Once the fire was extinguished, they learned the two children did not survive, he said.

“We got here in a timely matter. We got water on the fire and we made our searches, which revealed two deceased people,” he said. “The fire had advanced to the stage where it was open, free-burning.”

The cause of the fire is still under investigation, Mungovan said.

But authorities are looking closely at the hot plate that was found in the bedroom, said Larry Langford, a spokesman for the Fire Department.
 
“There is no official cause yet,” Langford said. “We did not find one working smoke detector in that building.”
 
On Saturday morning, a crew of firemen went door to door on the block offering free smoke detectors to neighbors and talking to them about fire safety.

Ald. Toni Foulkes, 15th, said she arrived to the house about an hour after the fire was reported.

Officials from the Fire Department told her the blaze apparently was started by a hot plate that was being used to heat a bedroom, she said.

“This was senseless,” Foulkes said, shaking her head as she stood outside the two-story grey-stone building. “The oldest (boy), he was just terrified. It bothers me.”

Earlier that morning, as firefighters battled the blaze, neighbors Michelle Washington and Tiffany Williams saw the two boys standing outside without coats and shoes, they said.

They invited the boys into their home to keep warm.

Darnell and Marquis told the women their mother and aunt went to a party at the “haunted house” and told them to go to sleep, Washington said. When the boys woke up, they saw the fire and smoke.

“They looked shaken and scared,” Washington said.

It was at Washington's home that investigators from the Bomb and Arson unit and the Office of Fire Investigations interviewed the boys, the women said.

The children were later taken into protective custody by the Department of Children and Family Services.

News of the younger children’s deaths shook up the West Englewood block and riled up neighbors, who said they often saw Darnell walking home alone from school.

Some neighbors said there was no gas service at the house, which is why the family was using the hot plate to keep warm.

The family had lived on the block for about a year and a half, said neighbor Ken Allison. Neighbors often saw the women with their children, he said, but they were not well known.

“There’s no way they should have left those kids alone,” he said, his voice rising with indignation. “There’s no room to half-step as a parent. There’s too much going on.”

When firefighters arrived around 3:30 a.m., they weren't able to get into the home because of intense heat and fire, a Chicago Fire Department official said. Fire was heavy throughout the basement and first floor, he said.

Firefighters cut through burglar bars on the windows, he said.

Firefighters eventually found the two children cuddled up in a bed, fire officials said at a news conference.

The basement windows were all shattered. A white Christmas tree, smudged with smoke, stood near front room window.

A neighbor told an investigator that the second-floor tenants recently moved out of the brick and stone two-flat.

pnickeas@tribune.com

Twitter: @PeterNickeas

lbowean@tribune.com
Twitter: @lollybowean

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Americans answer D.C.’s siren song of employment, strong economy

WASHINGTON (Reuters) – Thirteen years ago the band The Magnetic Fields crooned that the U.S. capital city is “the greatest place to be,” in the indie love song “Washington, D.C.”

Recently, a growing number of Americans are singing along as they move to the District in search of jobs, economic opportunity and cultural attractions.

In a study on migration provided exclusively to Reuters that is set to be released next month, United Van Lines found the District of Columbia tops all 50 states for the number of people moving in during 2012.

The city has held that spot for five years running, with 64 percent of the household moves in Washington coming from outside the city in 2012.

United Van Lines is the largest moving company in the country for households.

Oregon ranked second, followed by Nevada, North Carolina and South Carolina. Washington is a city that does not belong to a state, but is subject to loose control from the federal government.

“Washington, D.C., is unique because over the last five years its unemployment rate was not hit as hard by the Great Recession,” said Michael Stoll, chair and professor of public policy at the University of California at Los Angeles about the study. “But I think the other thing is that the city has remade itself from the one we knew 10 to 15 years ago.”

Washington has shed its reputation as the crime capital of the country, and it has developed a high technology corridor and other businesses that are both stable and hiring, said Stoll.

Also, many members of the Baby Boom generation are moving in as they retire, taking advantage of the free museums, monuments and cultural events the city has to offer, he said.

The rising popularity could yield a result also unthinkable less than two decades ago.

“D.C. will not just be a place of tourism. It will be a major economic engine, which many of us haven’t thought of it as being before,” Stoll said.

A U.S. Census report released on Thursday also showed the city is gaining new residents. Washington’s population increased 2.15 percent between July 2011 and July 2012, a rise second only to North Dakota.

The District’s population increase of 5.1 percent from 2010 to 2012 was the biggest in the country, the Census found. It had had 632,323 residents as of July 1.

The city has a large international community, largely due to the presence of foreign embassies and organizations such as the World Bank. The Census found people from other countries made up 32 percent of the net migration from 2011 to 2012.

According to a Labor Department report released on Friday, the District’s unemployment rate fell in November to 8.1 percent from 10.1 percent the year before. Local political leaders point to a development boom and one of the highest median incomes in the country – $ 63,124 – as other draws to the city.

On a national level, Stoll said, the migration patterns show Americans are seeking economic opportunity in places where new manufacturing and technology enterprises are building up. The patterns reveal a swelling group of aging people who are retiring and looking for affordable and comfortable places to live, as well.

He added that many people who wanted to move to California, but were put off by the state’s economic woes, turned their moving vans north to Oregon.

New Jersey topped states for outward moves, in 2012, the United Van Lines study showed, largely due to a shrinking factory sector. It was followed by Illinois, West Virginia, Michigan and New York.

Washington’s popularity surge recently created a paradox in the city’s economic success story. Last month, the Brookings Institution concluded three U.S. metropolitan areas are in economic recovery, but did not include Washington because its population burst drove down its gross domestic product on a per capita basis.

(Reporting By Lisa Lambert; Editing by Leslie Adler)

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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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Emanuel explores Midway privatization

Mayor Rahm Emanuel's administration will explore the possibility of privatizing Midway Airport but will take a shorter-term, more tightly controlled approach than was employed by former Mayor Richard Daley's team on the city's first go-round.

Chicago's last try, a 99-year lease that would have brought in $2.5 billion, died in 2009 when the financial markets froze up.

The city's latest intentions are expected to be formally announced Friday, ahead of a Dec. 31 deadline for deciding whether to retain a slot for Midway in the Federal Aviation Administration's airport privatization pilot program. The city put off this decision several times previously.

The move, preliminary as it is, is sure to be politically charged, given the anger over the way Daley's 75-year parking meter privatization deal has played out, with proceeds used to plug operating deficits and meter rates rising sharply.

With that historical backdrop, Emanuel is suggesting a more conservative approach. It includes a shorter-term lease of less than 40 years; a "travelers' bill of rights" aimed at ensuring any changes will benefit passengers; and a continuing stream of revenue for the city, giving it a shot to capture some growth.

And unlike the parking meter and Chicago Skyway lease deals, a new Midway transaction would not allow proceeds to be used to plug operating deficits or to pay for operations in any way, Emanuel said in an interview Thursday.

"I will not let the city use it as a crutch to not make the tough decisions on the budget," he said.

But while a shorter lease and greater city control may play well locally, those sorts of terms may not appeal to investors, experts said in interviews this month.

"The shorter the lease term, the lower the bid prices are going to be — that's just the math," said Steve Steckler, chairman of the Infrastructure Management Group, a Bethesda, Md.-based company that advises infrastructure owners and operators. "I'd be shocked if investors offered more than $2 billion for a 40-year lease," Steckler said.

Emanuel said: "Nobody knows until you talk to people. … I'm the mayor and I'm not agreeing to … 99 years. I'm saying it's either 40 years or less." His office has not offered an estimate of what such a deal could bring in, saying it would be premature.

"No final decisions have been made, but we can't make a decision until we evaluate fully if this could be a win for Chicagoans," Emanuel said.

A private operator would take over management of such revenue-producing activities as food, beverage and car rental concessions and parking lots. The FAA would continue to provide air traffic control, while the Transportation Security Administration would continue to provide security operations. The city would retain ownership.

Few details were provided about how privatization would affect travelers and Midway employees. Emanuel said specifics will emerge over time.

By year's end, the city will send the FAA a preliminary application, a timetable and a draft "request for qualification," a document the city will put out early next year to identify qualified bidders for the project. A review of the potential bidders will be conducted in the spring.

Last year, Emanuel expressed hesitation in pursuing a private lease for Midway unless a careful vetting process was in place, saying taxpayers were correct to be wary, given the city's history.

The evaluation process will be deliberate and open to public view, he said Thursday.

He pledged to create a committee of business, labor and civic leaders that will provide updates to the public on a regular basis and that will select an independent adviser to vet the transaction. The committee will deliver a report to the City Council, and there will be a 30-day review period before any vote.

"I set up a different process and a different set of principles that stand in stark contrast to what was discussed or done in the past," Emanuel said.

The FAA pilot program frees cities from regulations that require airport revenue to be used for airport purposes. It allows money to be withdrawn for other uses.

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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)

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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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About New York: One Boy’s Death Moves State to Action to Prevent Others

Prompted by the death of a 12-year-old Queens boy in April, New York health officials are poised to make their state the first in the nation to require that hospitals aggressively look for sepsis in patients so treatment can begin sooner. Under the regulations, which are now being drafted, the hospitals will also have to publicly report the results of their efforts.

The action by New York has elated sepsis researchers and experts, including members of a national panel who this month formally recommended that the federal government adopt standards similar to what the state is planning.

Though little known, sepsis, an abnormal and self-destructive immune response to infection or illness, is a leading cause of death in hospitals. It often progresses to severely low blood pressure, shock and organ failure.

Over the last decade, a global consortium of doctors, researchers, hospitals and advocates has developed guidelines on early identification and treatment of sepsis that it says have led to significant drops in mortality rates. But first hints of the problem, like a high pulse rate and fever, often are hard for clinicians to tell apart from routine miseries that go along with the flu or cold.

“First and foremost, they need to suspect sepsis,” Dr. Mitchell M. Levy, a professor at Brown University School of Medicine and a lead author of a paper on the latest sepsis treatment guidelines to be published simultaneously next month in the United States in a journal, Critical Care Medicine, and in Europe in Intensive Care Medicine.

“It’s the most common killer in intensive care units,” Dr. Levy said. “It kills more people than breast cancer, lung cancer and stroke combined.”

If started early enough, the treatment, which includes antibiotics and fluids, can help people escape from the drastic vortex of sepsis, according to findings by researchers working with the Surviving Sepsis Campaign, the global consortium. The tactics led to a reduction of “relative risk mortality by 40 percent,” Dr. Levy said.

Although studies of 30,000 patients show that the guidelines save lives, “the problem is that many hospitals are not adhering to them,” said Dr. Clifford S. Deutschman, director of the sepsis research program at the Perelman School of Medicine at the University of Pennsylvania and the president of the Society of Critical Care Medicine.

About 300 hospitals participate in the study, and the consortium has a goal of having 10,000. “The case is irrefutable: if you take these sepsis measures, and you build a program to help clinicians and hospitals suspect sepsis and identify it early, that will mean more people will survive,” Dr. Levy said.

At a symposium in October, the New York health commissioner, Dr. Nirav R. Shah, said that he would require state hospitals to adopt best practices for early identification and treatment of sepsis. Gov. Andrew M. Cuomo intends to make it a major initiative in 2013, said Josh Vlasto, a spokesman for the governor. “The state is taking unprecedented measures to prevent and effectively treat sepsis in health care facilities across the state and is looking at a wide range of additional measures to better protect patients,” Mr. Vlasto said.

In April, Rory Staunton, a sixth grader from Queens, died of severe septic shock after he became infected, apparently through a cut he suffered while playing basketball. The severity of his illness was not recognized when he was treated in the emergency room at NYU Langone Medical Center. He was sent home with a diagnosis of an ordinary bellyache. Hours later, alarming laboratory results became available that suggested he was critically ill, but neither he nor his family was contacted. For an About New York column in The New York Times, Rory’s parents, Ciaran and Orlaith Staunton, publicly discussed their son’s final days. Their revelations prompted doctors and hospitals across the country to seek new approaches to heading off medical errors.

In addition, Commissioner Shah in New York convened a symposium on sepsis, which included presentations from medical experts and Rory’s parents.

At the end of the meeting, Dr. Shah said that he had listened to all the statistics on the prevalence of the illness, and that one had stuck in his memory: “Twenty-five percent,” he said — the portion of the Staunton family lost to sepsis.

He said he would issue new regulations requiring hospitals to use best practices in identifying and treating sepsis, actions that, he said, he was taking “in honor of Rory Staunton.”

The governor’s spokesman, Mr. Vlasto, said that “the Staunton family’s advocacy has been essential to creating a strong public will for action.”

Dr. Levy said New York’s actions were “bold, pioneering and grounded in good scientific evidence,” adding, “The commissioner has taken the first step even before the federal government.”

Dr. Deutschman said that initiatives like those in New York were needed to overcome resistance among doctors. “You’re talking about a profession that has always prided itself on its autonomy,” he said. “They don’t like to be told that they’re wrong about something.”

The availability of proven therapies should move treatment of sepsis into a new era, experts say, comparing it to how heart attacks were handled not long ago. People arriving in emergency rooms with chest pains were basically put to bed because not much could be done for them, said Dr. Kevin J. Tracey, the president of the Feinstein Institute for Medical Research at North Shore-Long Island Jewish Health System. Dr. Tracey, a neurosurgeon, has made major discoveries about the relationship between the nervous system and the runaway immune responses of sepsis.

If physicians and nurses were trained to watch for sepsis, as they now routinely do for heart attacks, many of its most dire problems could be headed off before they got out of control, he said. The Stauntons have awakened doctors and nurses to the possibility of danger camouflaged as a stomach bug.

“We are with sepsis where we were with heart attack in the early 1980s,” Dr. Tracey said.

“If you don’t think of it as a possibility, this story can happen again and again. This case could change the world.”

E-mail: dwyer@nytimes.com

Twitter: @jimdwyernyt

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