Corporate tax rate overhaul may be part of a 'fiscal cliff' deal

WASHINGTON — Amid the wrangling over the so-called fiscal cliff, President Obama and congressional Republicans can agree on something: They want to lower the corporate tax rate.

The U.S. has the highest overall rate of any of the world's developed economies. It took the top spot in March after Japan reduced its rate, mimicking other countries that have lowered taxes to lure new businesses and keep existing companies from leaving.

Negotiations to avert automatic income tax increases and federal spending cuts scheduled to kick in Jan. 1 could provide the impetus for U.S. policymakers to tackle an overhaul of the corporate tax code next year.

The White House wants to put a corporate tax overhaul, along with changes to the individual income tax system, on a fast track as part of any deal to avoid the "fiscal cliff."

The centerpiece of an overhaul would be slashing the 35% corporate tax rate, a goal long sought by corporate executives and lobbyists.

Quiz: How much do you know about the 'fiscal cliff'?

"In the name of global competitiveness, I think that has largely been agreed to," Jim McNerney, chief executive of Boeing Co., said about how both parties view the need for major corporate tax changes.

In February, Obama proposed lowering the federal rate to 25% for manufacturing companies and to 28% for other firms. Rep. Dave Camp (R-Mich.), chairman of the House Ways and Means Committee, has been pushing a plan to lower the rate to 25% for all corporations.

In both cases, the rate cuts would be accompanied by the elimination of some of the numerous tax breaks that allow many companies to pay a much lower effective tax rate — and sometimes to avoid paying any corporate taxes at all.

"The administration's position on this is very much in sync with what Republicans say they want, which is a lower rate and a broader base," said Jared Bernstein, a senior fellow at the Center on Budget and Policy Priorities and the former chief economist for Vice President Joe Biden.

But there still are some obstacles to a deal.

Some Democrats want to use an overhaul to increase the amount of tax revenue coming from corporations, while Republicans want to keep the amount the same. The White House and congressional Republicans also differ on how the U.S. should treat money earned abroad.

And the business community itself is divided. Many small companies file taxes as individuals. They're opposed to any "fiscal cliff" deal that would raise their rates while giving corporations a rate reduction.

Analysts said the obstacles could be overcome because there is consensus around the broader point that the U.S. needs to bring its corporate tax rate in line with other developed nations.

"Regardless of your political persuasion, it is unquestionably the case that the nominal U.S. corporate tax rate is much higher than that of peer countries," said Edward Kleinbard, a USC law professor and former chief of staff of Congress' Joint Committee on Taxation.

The case for corporate tax reform got a boost when the overall U.S. rate of 39.1%, which includes federal, state and local corporate taxes, became the highest this year among the 34 nations in the Organization for Economic Cooperation and Development. Two decades ago, the U.S. was 13th.

"At one time in the '80s, we had a competitive corporate tax rate," said Dorothy Coleman, vice president of tax and domestic economic policy for the National Assn. of Manufacturers. "We've fallen behind by standing still."

Quiz: The year in business

But the rate in the tax code isn't what many companies pay because of a host of deductions and tax credits. In 2011, the effective corporate tax rate in the U.S. was 29.2%, roughly in line with the 31.9% average of the six other largest developed economies, the Obama administration said.

The White House said that parity does not mean the statutory rate shouldn't be reduced. It simply means that many tax breaks should be eliminated, allowing the rate to be lowered without adding to the deficit.

Read More..

Two firefighters die in ambush at blazing New York house

A gunman ambushed four volunteer firefighters responding to an intense pre-dawn house fire Monday morning outside Rochester, N.Y., killing two before ending up dead himself, authorities said. Police used an armored vehicle to evacuate more than 30 nearby residents.

The gunman fired at the firefighters when they arrived shortly after 5:30 a.m. at the blaze near the Lake Ontario shore in Webster, town Police Chief Gerald Pickering said. The first Webster police officer who arrived chased the suspect and exchanged gunfire with him, authorities said.

"It does appear it was a trap" for the first responders to the fire, Pickering said at a news conference.

Authorities didn't say how the gunman died or whether anyone might have died in the fire itself.

One of the dead firefighters was also a town police lieutenant; it wasn't clear whether he returned fire. An off-duty police officer who was driving by was injured by shrapnel, Pickering said.

The fire started in one home and spread to two others and a car, officials said. The gunfire initially kept firefighters from battling the blazes. Police say four homes were destroyed and four damaged.

The West Webster Fire District learned of the fire early Monday after a report of a car and house on fire on Lake Road, on a narrow peninsula where Irondequoit Bay meets Lake Ontario, Monroe County Sheriff Patrick O'Flynn said.

The fire appeared from a distance as a pulsating ball of flame glowing against the early morning sky, flames licking into treetops and reflecting on the water, with huge bursts of smoke billowing away in a brisk wind.

Two of the firefighters arrived on a fire engine and two in their own vehicles, Pickering said. After the gunman fired, one of the wounded men managed to flee, but the other three couldn't because of flying gunfire.

A police armored vehicle was used to recover two of the men, and eventually it evacuated 33 people from nearby homes, the police chief said.

The dead men were identified as Police Lt. Michael Chiapperini, 43, the Webster Police Department's public information officer; and Tomasz Kaczowka, also a 911 dispatcher, whose age was not released.

Pickering described Chiapperini as a "lifetime firefighter" with nearly 20 years with the department, and called Kaczowka a "tremendous young man."

The two wounded firefighters, Joseph Hofsetter and Theodore Scardino, were in guarded condition in the intensive care unit at Strong Memorial Hospital, authorities said. Both were awake and alert and are expected to recover.

Hofsetter, also a full-timer with the Rochester Fire Department, was hit once in the pelvis, and the bullet lodged in his spine, authorities said. Scardino was hit in the chest and knee.

Monday's shooting and fires were in a neighborhood of seasonal and year-round homes set close together across the road from the lakeshore. The area is popular with recreational boaters but is normally quiet this time of year.

"We have very few calls for service in that location," Pickering said. "Webster is a tremendous community. We are a safe community, and to have a tragedy befall us like this is just horrendous."

O'Flynn lamented the violence, which comes on the heels of other shootings including the massacre of 20 students and six adults at Sandy Hook Elementary School in Newtown, Conn.

"It's sad to see that that this is becoming more commonplace in communities across the nation," O'Flynn said.

Webster, a middle-class suburb, now is the scene of violence linked to house fires for two Decembers in a row.

Last Dec. 7, authorities say, a 15-year-old boy doused his home with gasoline and set it ablaze, killing his father and two brothers, 16 and 12. His mother and 13-year-old sister escaped with injuries. He is being prosecuted as an adult.

Read More..

Thousands sign US petition to deport Piers Morgan

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

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

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

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

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

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

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

Read More..

News Analysis: Scientists to Seek Clues to Violence in Genome of Gunman in Newtown, Conn.

In a move likely to renew a longstanding ethical controversy, geneticists are quietly making plans to study the DNA of Adam Lanza, 20, who killed 20 children and seven adults in Newtown, Conn. Their work will be an effort to discover biological clues to extreme violence.

The researchers, at the University of Connecticut, confirmed their plans through a spokeswoman but declined to provide details. But other experts speculated that the geneticists might look for mutations that might be associated with mental illnesses and ones that might also increase the risk for violence.

They could look at all of Mr. Lanza’s genes, searching for something unusual like gene duplications or deletions or unexpected mutations, or they might determine the sequence of his entire genome, the genes and the vast regions of DNA that are not genes, in an extended search for aberrations that could determine which genes are active and how active they are.

But whatever they do, this apparently is the first time researchers will attempt a detailed study of the DNA of a mass killer.

Some researchers, like Dr. Arthur Beaudet, a professor at the Baylor College of Medicine and the chairman of its department of molecular and human genetics, applaud the effort. He believes that the acts committed by men like Mr. Lanza and the gunmen in other rampages in recent years — at Columbine High School and in Aurora, Colo., in Norway, in Tucson and at Virginia Tech — are so far off the charts of normal behavior that there must be genetic changes driving them.

“We can’t afford not to do this research,” Dr. Beaudet said.

Other scientists are not so sure. They worry that this research could eventually stigmatize people who have never committed a crime but who turn out to have a genetic aberration also found in a mass murder.

Everything known about mental illness, these skeptics say, argues that there are likely to be hundreds of genes involved in extreme violent behavior, not to mention a variety of environmental influences, and that all of these factors can interact in complex and unpredictable ways.

“It is almost inconceivable that there is a common genetic factor” to be found in mass murders, said Dr. Robert C. Green, a geneticist and neurologist at Harvard Medical School. “I think it says more about us that we wish there was something like this. We wish there was an explanation.”

Scientists are well aware of the fraught history behind the questions of biology and violence.

In the early 20th century, claims that criminal behavior was inherited arose during the eugenics movement and led to sterilizations of mental patients and felons.

On Christmas Day in 1965, two researchers published a paper saying men with an extra Y chromosome, the chromosome that confers maleness, were “super males” and born criminals. The hypothesis was helped along by the fact that these men “fit the classic Hollywood criminal — big, awkward, thuglike and with low I.Q.’s,” said Dr. Philip Reilly, a lawyer and clinical geneticist who has studied this history.

The idea persisted for about 15 years, Dr. Reilly said, but eventually the epidemiological evidence convinced scientists that it was wrong — that these men were no more violent than men without an extra Y chromosome.

In 1993, in a paper published in the journal Science, researchers reported that a mutation leading to a lack of the enzyme monoamine oxidase caused violence in a Dutch family. Every family member who inherited the mutation was a violent criminal; those without it had no criminal behaviors.

“It was a stunning piece of work,” said James Blair, the chief of the unit on affective cognitive neuroscience at the National Institute of Mental Health. But, he added, it turned out not to be generalizable. For the most part, “it was just this family,” he said.

The National Institutes of Health was embroiled in controversy about 20 years ago simply for proposing to study the biological underpinnings of violence. Critics accused researchers of racism and singling out minorities, especially black men.

Shortly after, the N.I.H. took back financing for a conference at the University of Maryland to examine genetics and criminal behavior. The conference was canceled.

But genetics has come of age in recent years with new and powerful methods to determine DNA sequences and analyze the results. Studies of people at the far end of a bell curve can be especially informative, because the genetic roots of their conditions can be stark and easy to spot, noted J. H. Pate Skene, a Duke University neurobiologist.

“I think doing research on outliers, people at an end of a spectrum on something of concern like violent behavior, is certainly a good idea,” he said, but he advised tempering expectations.

“I would call it a caution, not about whether to do this research but about what to expect,” he added.

Perhaps it will be fruitless to search for one or a few major gene mutations that always lead to extreme violence, Dr. Beaudet said. But what if a significant fraction of the shootings were linked to gene variants? What if scientists were to discover genes that were risk factors, increasing a person’s chance of violent behavior but not foreordaining it?

“If we know someone has a 2 percent chance or a 10 percent chance or a 20 percent chance of violent behavior, what would you do with that person?” Dr. Skene said. “They have not been convicted of anything — have not done anything wrong.”

But a genetic profile might play a role if someone were convicted of violent offenses, Dr. Beaudet countered. Criminals are routinely denied parole based solely on psychiatric evaluations. Perhaps a genetic test could add to the certainty of the decision, he said.

Ultimately, understanding the genetics of violence might enable researchers to find ways to intervene before a person commits a horrific crime. But that goal would be difficult to achieve, and the pursuit of it risks jeopardizing personal liberties. Some scientists shudder at the thought of labeling people potential violent criminals.

“The idea of screening with a view of preventing those kinds of incidents is basically unthinkable,” said Dr. Steven E. Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T. “You would fail. You would stigmatize.”

Some day, he added, it might be important to know the phenotypes — the characteristics — of violent killers and have their DNA, but not for the reasons many think.

“I am always happy to store DNA and phenotype information and freeze cells, thinking that one day we would have usable clues,” Dr. Hyman added. “But that would be biology, not prevention.”

Read More..

Dockworker strike looms at Eastern Seaboard and Gulf Coast ports

The nation's retailers, manufacturers and farmers are bracing for a possible strike that could idle U.S. ports all along the Eastern Seaboard and Gulf Coast.

That walkout could begin as early as Sunday after the midnight Saturday expiration of a 90-day extension of a contract between the International Longshoremen's Assn. and several shipping lines, terminal operators and port associations.

It would be the first strike by the ILA in 35 years.

U.S. military shipments and so-called "bulk" cargo that is not carried in 20-foot to 40-foot long steel cargo containers would not be affected. But the vast majority of the goods sold by U.S. retailers would be affected, as would a portion of the country's agricultural exports.

Until negotiations broke down last week, the union and the U.S. Maritime Alliance Ltd -- a group of ocean cargo shipping lines, cargo terminal operators and port associations at 14 U.S. harbors -- had been trying to iron out terms of a new six-year contract.

One economist who tracks international trade called the dispute a contest of wills between some of the world's biggest cargo operators and one of the nation's strongest labor unions.

The biggest issue of contention involves so-called container royalty fees on cargo, which supplement dockworker wages. Employers want to cap those fees and limit who gets them. The union says the royalty fees should not be changed.

"The shipping industry is trying to take back some of the power," said economist John Husing, founder of Economics and Politics Inc. in Redlands, "but they are up against a union that has abnormal power for its size and one that is in a very strong position."

The ILA says it represents a total of 65,000 dockworkers on the East and Gulf coasts as well as on several major U.S. rivers and the Great Lakes and in Puerto Rico and Eastern Canada.

The impact of a strike would be mitigated by one thing: This is the slowest season for cargo coming by sea into the U.S. Shippers have usually moved their goods for the busy holiday retail season by October.

Even so, a "failure to reach a contract agreement would result in a coast-wide shutdown at 14 containerized ports – from Maine to Texas – which would have serious economy-wide impacts," the retail federation and coalition of national and state organizations said in a letter sent last week to President Obama.

The letter urged the president to take all steps at his disposal to get both sides back to the bargaining table and keep the cargo moving.

Late last month, most of the Port of Los Angeles and half of the Port of Long Beach were shut down during an eight-day strike by the clerical unit of the International Longshore and Warehouse Union.

The ILWU, which represents West Coast dockworkers, is not affiliated with the ILA.

Meanwhile, management at three of the four grain terminal operations at ports in the Pacific Northwest have given union dockworkers a deadline of noon today to accept their final contract offer.

A strike or a lockout at those terminals would strand millions of dollars of U.S. agricultural exports destined for sale overseas.

ALSO:

Herbalife stock still tumbling

Gun sales still surging across U.S.

And the stock market is falling on a short trading day

Read More..

Raging fire guts Kabul market

KABUL, Afghanistan -- Firefighters battled through the night to contain a raging fire that swept through a market in the Afghan capital.

No injuries were reported, but the blaze destroyed hundreds of stores and millions of dollars worth of merchandise, Afghan police and firefighters said at the scene. 

Dealers at the neighboring currency exchange, the city’s largest, said they evacuated cash, computer equipment and records from their shops as the flames approached during the night. But in the morning, the market was jammed with people haggling over thick stacks of notes as smoke billowed overhead.

Col. Mohammed Qasem, general director of the Kabul fire department, said he suspected an electrical short was to blame for the fire. 

Gas canisters used to heat the stores propelled the flames, along with the cloth and clothing sold by many of the vendors, Qasem said. “It made it very big in a short time.”

Firefighters from the Afghan defense department and NATO forces were sent to assist. But the city’s notorious traffic and the market’s narrow lanes made it difficult for responders to maneuver their vehicles, Qasem said.

Abdulrahman, who like many Afghans has only one name, squatted near a fire truck with his head in his hands  as responders aimed a hose at the blackened ruins of a building still smoldering at noon Sunday, more than 12 hours after the fire broke out.

He said the building had contained three shops that he owned and a warehouse full of glassware, crockery and kitchen utensils. 

“I lost everything,” he said.

Shirali Khan complained that police hadn't allowed him to remove the goods from his four clothing stores.

“They thought we were all robbers,” he said.  “There’s only ashes left.”

ALSO:

Pope pardons former butler convicted of theft

Bombing kills local official, 7 other people in Pakistan

Tensions high as vote on proposed Egyptian constitution continues

Special correspondent Hashmat Baktash contributed to this report.

Read More..

'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.

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.

___

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.

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..

Association board can't use email instead of meetings

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

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

Doesn't this violate some kind of law?

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

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

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

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

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

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

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

Read More..

This bus' next stop: doing good

Maybe you want to help others. Maybe you long to lend a hand. But you're not sure where and you're not sure how and you don't know who to call.

You could ask around. Or you could book a seat on the Do Good Bus.

You will pay $25. You will get a box lunch. You will put yourself in the hands of a stranger.

CITY BEAT: Life in the Southland

When the bus takes off, you will not know where you are going — only that when you get there, you will be put to work.

You find yourself on this weekday afternoon one of an eclectic group, gathered a little shyly on an East Hollywood curb.

There's a Yelp marketer, a grad student, an actor, a novelist, a Manhattan Beach mother with her son and daughter, who just got home from prep school and college.

You see a school bus pull up. You step on board. It feels nostalgic, like day camp or a field trip.

Rebecca Pontius welcomes you, wearing jeans and sneakers and a black fleece vest. She looks like the kind of person who would plunge her hands deep into dirt, who wouldn't be afraid of the worms, who could lead you boldly.

The bus takes off, and Pontius stands toward the front, sure-footed. She founded the Do Good Bus, she tells you, to 1) build awareness, 2) build community, 3) encourage continued engagement.

Oh, she says, and to 3a) have fun. Hence the element of mystery, the faux holly branches that decorate some of the rows of seats, the white felt reindeer antlers she's wearing on her head.

She smiles a wide, toothy smile that makes you automatically reciprocate.

So you go along when she asks you to play get-to-know-you games. Even though you're embarrassed, you don't object when she assigns you one of the 12 days of Christmas to sing and act out when it's your turn.

Everyone's singing and laughing as the bus fits-and-starts down the freeway.

Maids-a-milking, geese-a-laying, bus-a-exiting somewhere in South Los Angeles.

It stops outside a boxy blue building — the Challengers Boys and Girls Club — where, finally, Pontius tells you you'll be helping children in foster care build the bicycles that will be their Christmas gifts.

She did it last year, she says. It was great. And she's brought along some powder that turns into fake snow, which the kids will like.

You step inside a large gym, where nothing proceeds quite as expected.

It's the holiday season, so way too many volunteers have shown up. The singer Ne-Yo is coming to lead a toy giveaway. There's a whole roomful of presents the children can choose from, including pre-assembled bikes — which means no bikes will need to be built.

You stand and you sit and you wait. Then the kids come. You try to help where you can — making sure they get in the right lines, handing out raffle tickets.

You see their joy at getting gifts, which is nice. You're in a place you might not ordinarily be, which is interesting. And as the children head out, you offer them snow. You put the powder in their cupped hands. You add water. The white stuff grows and begins to look real. It's even cold.

It makes them go wide-eyed. It makes them laugh. And you feel such moments of simple happiness are something.

It's chilly as you wait to get back on the bus. You get in a group hug with your fellow bus riders, who seem like old friends.

On the trip back in the dark, Pontius plays Christmas music. She serves you eggnog in Mason jars.

And she says she's sorry your help wasn't more needed today.

She promises the January ride will be more hands-on.

Come or don't, she tells you. But whatever you do, find a way to do something.

nita.lelyveld@latimes.com

Follow City Beat @latimescitybeat on Twitter or at Los Angeles Times City Beat on Facebook.

Read More..