LONDON ? Veteran British broadcaster Jimmy Savile, a famously eccentric culture figure, has died at his home in northern England. He was 84.
Savile, known for his garish tracksuits, chunky gold jewelry and boundless enthusiasm for pop music and charity work, was the host of two long-running British television programs and claimed to have been a longtime confidant to Prince Charles and ex-Prime Minister Margaret Thatcher.
Rarely seen without his trademark large cigar, Savile had initially worked in a coal mine as a teenager before embracing music and built a national profile as a disc jockey ? first in Britain's dance halls and later on radio, including the renowned Radio Luxembourg.
West Yorkshire Police confirmed that officers had been called Saturday to Savile's home in the city of Leeds, northern England, and said that there were no suspicious circumstances surrounding his death. The cause of Savile's death is not yet known.
Savile claimed have been the first DJ in the world to use two turntables ? enabling continuous music to be played ? inventing the techniques later embraced by modern dance music, and to have pioneered the use of record, rather than live bands, at nightclubs.
"History has it that I was the very, very first in the whole world" to organize a disco event, he told the BBC in May.
Bestowed with a knighthood for his charity fundraising, Savile was best known as the host of the BBC's "Top Of The Pops" weekly television pop music show, launching the program in 1964 and returning to present its final edition in 2006.
For almost 20 years from 1975, Savile also hosted the hugely popular series "Jim'll Fix It," in which the broadcaster responded to children's letters by arranging for their wishes to be realized.
Savile championed a host of good causes ? frequently running marathons to raise money ? and led work to collect 20 million pounds ($32 million) for the creation of a national spinal injuries center at Stoke Mandeville Hospital in southern England.
"He was a very energetic character," friend and fellow radio presenter David Hamilton told Britain's Sky News television. "But most of all, I remember him as just a totally flamboyant, over the top, larger than life character and as he was on the air, he was just the same off."
Savile never married and lived alone in his native Leeds, in northern England, reserving part of his home as shrine to his later mother.
His guarded, and sometime curious, private life was the subject of a much watched television documentary in 2000 by film maker Louis Theroux, son of author Paul Theroux.
The Obama administration has ordered an independent review of loans made by the Energy Department to energy companies ? a clear response to the controversial and now-bankrupt Solyndra Inc. solar energy company.
It?s the latest step in the face of growing criticism over the $528 million government loan to Solyndra, which was part of the administration?s economic stimulus package meant to advance green energy. Last month, FBI agents and investigators from the Department of Energy's Office of Inspector General searched Solyndra headquarters in California for documents and other information.
Heading the review announced Friday is former Treasury official Herbert Allison, who oversaw the Troubled Asset Relief Program, part of the 2008 Wall Street bailout.
"Today we are directing that an independent analysis be conducted of the current state of the Department of Energy loan portfolio, focusing on future loan monitoring and management," White House chief of staff Bill Daley said Friday afternoon ? the traditional time for burying announcements. "While we continue to take steps to make sure the United States remains competitive in the 21st century energy economy, we must also ensure that we are strong stewards of taxpayer dollars."
Announcement of the internal review of procedures dealing with Solyndra was not enough to satisfy congressional critics.
Leaders of the Energy and Commerce Committee subcommittee on oversight and investigations say they?ll meet this coming week to consider a resolution authorizing the issuance of a subpoena for internal White House communications relating to the Solyndra loan guarantee.
?Subpoenaing the White House is a serious step that, unfortunately, appears necessary in light of the Obama administration?s stonewall on Solyndra,? Fred Upton (R) of Michigan and Cliff Stearns (R) of Florida said in a statement. ?Since we launched the Solyndra investigation over eight months ago, the Obama administration has unfortunately fought us every step of the way, even forcing us to subpoena documents from [the White House Office of Management and Budget].?
Apparently, White House officials weren?t the only ones pushing special consideration for green energy.
Sen. Orrin Hatch (R) of Utah, who has criticized the Obama administration?s backing of Energy Department loan guarantees to Solyndra, pushed for more than $20 million in government funding for a clean energy firm in his home state, reports USA Today.
?Hatch aides [said] earlier this month that the Republican lawmaker had never pushed for taxpayer money to be used for Raser Technologies, which operated a geothermal power plant in southern Utah and also developed hybrid plug-in vehicles,? the newspaper reported Friday. ?But on Friday, Hatch spokesman Matthew Harakal said that after an internal audit following publication of the USA Today story on Hatch's support for Raser, the Utah senator's office found that Hatch actually requested seven earmarks for more than $20 million from 2006 to 2008 to help fund research and development projects for the automotive wing of the company.?
None of the requests were funded, and Raser Technologies filed for bankruptcy in April.
Meanwhile, the Solyndra scandal ? if that?s what it is ? has indirectly touched at least one Republican presidential hopeful.
?Mitt Romney is facing scrutiny this week for associating himself with a lobbyist whose firm worked for failed California solar panel company Solyndra,? The Hill newspaper in Washington reported this week. ?Lobbyist Alex Mistri co-hosted a Romney fundraiser Wednesday that included a number of lobbyists and members of Congress, held at the American Trucking Association near Capitol Hill.?
Also attending the Romney fundraiser co-hosted by lobbyist Mistri was Rep. Darrell Issa (R) of California, chairman of the House Committee on Oversight and Government Reform investigating Solyndra.
Material from the Associated Press was used in this report.
New Orleans Saints tight end Jimmy Graham (80) is tackled by St. Louis Rams cornerback Al Harris (31) during the first quarter of an NFL football game on Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Jeff Roberson)
New Orleans Saints tight end Jimmy Graham (80) is tackled by St. Louis Rams cornerback Al Harris (31) during the first quarter of an NFL football game on Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Jeff Roberson)
St. Louis Cardinals baseball manager Tony La Russa puts on a St. Louis Rams jersey before the start of an NFL football game between New Orleans Saints and the Rams Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Tom Gannam)
St. Louis Rams head coach Steve Spagnuolo, left, talks to St. Louis Cardinals baseball manager Tony La Russa before the start of an NFL football game between New Orleans Saints and St. Louis Rams Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Tom Gannam)
St. Louis Cardinals baseball players stand during the national anthem before an NFL football game between New Orleans Saints and St. Louis Rams on Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Tom Gannam)
St. Louis Rams quarterback A.J. Feeley (4) throws under pressure from New Orleans Saints' Aubrayo Franklin (99) during the first quarter of an NFL football game Sunday, Oct. 30, 2011, in St. Louis. (AP Photo/Kii Sato)
ST. LOUIS (AP) ? Perhaps inspired by the hometown Cardinals' stunning surge to the World Series title, the St. Louis Rams pulled off a shocker of their own.
Steven Jackson scored twice in his first 100-yard game in three seasons as the lowly Rams earned their first win this season, a 31-21 upset of the New Orleans Saints.
Drew Brees barely kept alive his touchdown pass streak on a meaningless score in the final seconds a week after throwing five in a 62-7 rout of the winless Indianapolis Colts. Brees was intercepted twice, too, with Darian Stewart's pick and 27-yard return putting the game away with 2:51 to go.
The NFC South-leading Saints (5-3) average a league-best 35 points, but never got on track against a defense ranked near the bottom of the league. The Rams (1-6) had a season-high six sacks after entering the game with just 11, three by Chris Long.
Saints pass catchers were bottled up by a secondary minus its top three players.
The Rams wore throwback jerseys in a nod to their 1999 Super Bowl championship team. Then there was the pregame appearance by the Cardinals, who brought their World Series trophy with them to help fire up a crowd growing accustomed to disappointment from the Rams. The game was sold out, but there were hundreds of empty seats.
Manager Tony La Russa donned a Sam Bradford jersey and Game 7 winner Chris Carpenter went out for the coin toss wearing a Jackson jersey.
Rams players attended Game 3 of the World Series in Texas last week ? Albert Pujols' three-homer game ? the night before their 34-7 loss to the Cowboys in Dallas.
All three Saints losses have come on the road. But they were favored by nearly two touchdowns against a franchise that has been staggeringly awful on both sides of the ball. Like the Colts a week earlier, the Rams were starting their backup quarterback.
A.J. Feeley made his second straight start in place of Bradford (high left ankle sprain), and had a touchdown pass in a mistake-free outing.
Jackson had 159 yards on 25 carries, including a 32-yard jaunt on fourth-and-2 to set up his second touchdown that made it 24-0 in the third quarter.
Jonathan Vilma got the Saints on the board after recovering Feeley's fumble on a sack by Malcolm Jenkins, and Pierre Thomas scored with 10 minutes left to cut the gap to 10.
The first quarter was scoreless, a victory in itself for the Rams, given they've been outscored 59-13 in the opening period. Then, shockingly, they took control.
They capitalized on a pair of turnovers to go up 17-0 at the break. Jackson scored on a 3-yard run two plays after rookie Robert Quinn's blocked punt, the first in three NFL seasons against Thomas Morstead. Josh Gordy's interception at the Saints 38 gave St. Louis another short field that led to Brandon Lloyd's 8-yard catch.
NEW YORK ? Before Smoking Man, there was Obama Girl. And who can forget JibJab?
A new ad featuring Herman Cain's smoking campaign manager Mark Block is the latest political video to become an overnight Web sensation. The ad, with Block taking a drag on a cigarette while Cain flashes a Cheshire cat grin, has had close to 1 million clicks on Cain's website since its debut.
Not long ago, paid television ads were the only way for candidates to be noticed. But now online viral videos have become a staple of American politics.
Some widely disseminated videos have been harmless fun, such as the ad produced by digital studio JibJab in 2004 showing rivals George W. Bush and John Kerry singing a hilarious rendition of "This Land."
Others have had a deeper impact, including Tina Fey's scathing depiction of 2008 Republican vice presidential nominee Sarah Palin as an ill-informed lightweight. Those sketches first appeared on NBC's "Saturday Night Live" but were widely shared online.
Cain, a little-known former pizza chain executive before joining the 2012 GOP race, has seen his popularity spike recently after a series of debates and his much-discussed tax plan. The smoking man ad, with its low production values and quirky imagery, has added to the sense of novelty about Cain's candidacy.
The Obama Girl video, in which a fetching young woman sang about her crush on the then-Illinois senator, went viral early in the campaign and reinforced the notion of Barack Obama as the cool and sexy alternative to his more established Democratic rival, New York Sen. Hillary Rodham Clinton.
But, Ken Goldstein, whose Campaign Media Analysis Group tracks political advertising, said that while online videos had the power to influence a race, paid television advertising still carried much more overall impact.
"The Internet preaches to the choir," Goldstein said. "It's a great way to raise money and mobilize supporters to work harder, which are not trivial things. But viral videos are not a way to mobilize passive and undecided voters, which television ads do."
Google Plus has added Instagram-like controls to its photo section. The service has always had basic editing, and because Google Plus shares its photo albums with Picasa any edits made there would propagate back from there. But building them in makes things so much easier. The new controls only work in the desktop version, and is [...]
by Alia Beard Rau - Oct. 27, 2011 12:00 AM The Arizona Republic
The Arizona Legislature may have to go back to the drawing board if it wants voters in 2012 to kill the state's public-funded Clean Elections campaign-finance program.
Maricopa County Superior Court Judge Dean Fink on Wednesday threw out a ballot measure the Legislature approved this year, saying it violated the requirement that constitutional amendments focus on a single subject.
Senate Concurrent Resolution 1025 would have asked voters to ban the spending of public funds for candidates participating in the state's Clean Elections program, as well as in Tucson's public campaign-finance program. It also would have transferred any funds remaining in either of those programs to the state's general fund, even though Tucson's program is funded with city money.
Fink said that while most of the resolution covers issues that "share a common purpose," sweeping Tucson's money is a separate subject entirely.
"The principle implicated in depriving municipal taxpayers of money they had chosen to spend on campaign funding is very different from the principle that public funding of campaigns should be prohibited," Fink said in his ruling.
Clean Elections gives a lump sum of public funds to participating statewide and legislative candidates who get a required number of $5 donations and agree not to accept money from special-interest groups. It draws its money primarily from voluntary donations made on tax-return forms and a surcharge tacked onto civil, criminal and traffic fines.
The Arizona Advocacy Network Foundation and other voter-advocacy groups challenged the resolution in court.
"Once again, those who believe elections should be bought by the highest bidder over-reached in their attempt to eliminate Clean Elections, the reform that allows statewide and legislative candidates to run without ties to Big Money special interests," foundation executive director Linda Brown said via e-mail. "This is another example of an attempt by the Legislature to grab power from cities and towns."
The state and other defendants could appeal the ruling to the Arizona Supreme Court. The Legislature also could consider a revised resolution next session and still have time to get it on the November 2012 ballot.
Goldwater Institute attorney Clint Bolick, who represented supporters of the resolution in court, said an appeal was unlikely.
"We won the most significant issue, which was whether a referendum could ban public campaign financing on a statewide basis. The funds diversion issue really is not very significant," Bolick said. "Given that we have lots of time with the Legislature to reshape the bill, that's probably the direction we'll go."
ROME ? A new mother herself, Penelope Cruz says her current film role as a single mom is one of the most beautiful characters she has ever played.
Cruz made a cameo appearance in Rome on Wednesday night on the eve of the Rome Film Festival. She had been in Bosnia recently filming Sergio Castellitto's "Venuto al Mondo" about a single woman who brings her teenage son to Sarajevo, where the boy's father died during the 1990s Bosnian conflict.
She told reporters being a mother is the strongest experience a woman can have. Cruz and husband actor Javier Bardem became parents of a baby boy in January. Cruz, stunning in a somber black suit, says every experience in life makes you change and grow.
HARTFORD, Conn. ? A Connecticut man whose murder conviction was overturned but later reinstated has died of colon cancer while awaiting a new appeal trial.
Ronald Taylor's lawyer issued a statement Wednesday saying Taylor died Tuesday in Cheshire after a two-year cancer fight.
Taylor and co-defendant George Gould were convicted of killing a New Haven grocery shop owner in 1993 and sentenced to 80 years in prison. Both were freed in April 2010 after a state judge ruled they were victims of "manifest injustice" and declared them "actually innocent." The judge's ruling came after a key witness recanted her trial testimony.
In July, the state Supreme Court reinstated the murder convictions, saying the judge was wrong to overturn them. Gould was sent back to prison; Taylor was allowed to remain out on bail.
New York ? Occupying lower Manhattan isn't for everyone. Here, suggestions for people seeking another focus for their frustrations
Recent polls show that anywhere from 32 percent to 54 percent of Americans are fans of the Occupy Wall Street movement, suggesting that at least 46 percent of us aren't excited about camping out in New York City's financial district. Luckily, this is a big country, and there are lots of places to "Occupy." Here are five suggestions:
1. Occupy Hollywood "The Great Recession is not Johnny Depp's fault," says Mary Elizabeth Williams at?Salon. "Johnny Depp did not decimate your 401K" or foreclose on your house. But he's definitely part of the 1 percent, and there's no way he and his fellow celebrities deserve tens of millions of dollars to make another stupid movie, especially while the "bloated and reckless" studios are laying off hundreds of employees: "It's time to Occupy Hollywood." That would serve those anti-capitalist Hollywood liberals right, says Lurita Doan at?Townhall. Nobody has done more than those Robin Hood-loving "pie-in-the-sky idealists" to demagogue businessmen and entrepreneurs.?
2. Occupy the Media It might be time to "forget about occupying Wall Street" and "occupy newsrooms" instead, says David Carr in The New York Times. "As newspapers all over the country struggle to divine the meaning of the Occupy protests," their marauding bosses at dying news empires like the Tribune Company and Gannett are engaging in the same financial shenanigans that "have left protesters enraged." Slashing newsroom jobs while paying themselves fat bonuses is great for media bosses, but bad for America.
3. Occupy Sesame Street Occupy Wall Street deserves more media attention, but that won't happen if we don't engage children, says Tauntr. "Kids drive the market and therefore the media," and they won't tune in unless you "pepper spray Snuffleupagus." So if you want OWS to succeed, "Occupy Sesame Street." I'm in, says Cory Doctorow at?BoingBoing. "After all, most of us learned how to think about concepts like 'fairness' from these characters." But Sesame Street already is occupied, by a new hunger-plagued, impoverished Muppet?named?Lily, says Alexandra Petri at?The Washington Post. "If the recession can penetrate to Sesame Street, then nothing is safe."
4. Occupy Art Galleries A splinter group left Occupy Wall Street's base camp in Zuccotti Park this weekend for a SoHo art gallery called Artists Space, says Colin Moynihan in The New York Times. The group, called Take Artists Space, pointed out that its "newly acquired space" had the advantages of a "luxurious bathroom and central heating." But they also had a gripe: The art world has become all about profits, not aesthetics, treating paintings and sculpture as little more than capital. The protesters were ejected on Sunday night, after a laptop was stolen. "Let's occupy something else," the group said Monday. "How can the rest of New York City remain unoccupied? It can't. We will occupy everything."
5. Occupy Your Mind "I don't blame the protesters for their anger at the system," but it's misdirected, says Michael Radkay at?International Business Times. "You don't need to occupy Wall Street," you need a job. And that means "you need to occupy your mind and use the energy you applied" to making signs and planning a giant protest to finding gainful employment. It's not like the protesters don't have skills: Employers love workers with the "ability to create a buzz" and leverage social media for free publicity.
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NEW ORLEANS?? More than six years after Hurricane Katrina's rampage, authorities have taken only halting steps toward identifying weaknesses in a nationwide patchwork of levees intended to protect millions of Americans' lives and property during potentially catastrophic floods.
The U.S. Army Corps of Engineers, accused of building substandard levees and floodwalls that failed when Katrina swamped the Gulf Coast in 2005, has spent $56 million since then developing the initial phase of a national levee inventory as required by Congress. The Corps on Thursday was releasing a database with information about nearly 14,000 miles of levees under its jurisdiction.
But the inventory doesn't include what is believed to be more than 100,000 additional miles of levees not covered by the Corps' safety program. Some are little more than mounds of earth piled up more than a century ago to protect farm fields. Others extend for miles and are made of concrete and steel, with sophisticated pump and drainage systems. They shield homes, businesses and infrastructure such as highways and power plants.
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The National Committee on Levee Safety, established after the Katrina disaster to evaluate the system and recommend improvements, issued a report in 2009 calling for the Corps to catalog and inspect every levee so deficiencies could be fixed. But Corps officials say Congress has not provided enough authority or money to add non-federal levees to the database, a massive undertaking that would take years.
"The reality is, we don't know how many levees are out there," said Eric Halpin, the Army Corps' special assistant for dam and levee safety and vice chairman of the levee safety committee. He acknowledged the inventory presently includes only about 10 percent of the likely total.
"I think we've done a great job putting forward a state-of-the-art tool," Halpin said. "It's a first step. It will be much more powerful once we can get all the data in there."
For each levee system, the database will include its location, design and rating following one or more safety inspections.
Inspection ratings from nearly 700 of the roughly 2,000 levee systems under the Corps' jurisdiction have been added to the database thus far, said spokesman Pete Pierce.
Of those, 77 percent had ratings of "minimally acceptable," meaning they have "minor deficiencies" that make the levees less reliable but are not expected to seriously impair their performance. An additional 11.6 percent were rated "unacceptable," or likely to fail during a flood, while 11.3 percent were graded as "acceptable," or without deficiencies.
Experts say the government is moving too slowly to complete the inventory.
"We need to be really candid with the American people," said Sam Riley Medlock, policy counsel for the Association of State Floodplain Managers and a member of the levee safety panel. "This is yet another class of infrastructure that is aging and posing risks and we're going to have to do something about it."
Levee network receives a D- Gerald Galloway, a former Army Corps district engineer and University of Maryland engineering professor, told a Senate committee this month the levee network has "significant" problems and received an overall grade of "D minus" from the American Society of Civil Engineers in 2009. The group estimated that $50 billion worth of improvements was needed over five years.
"So today hundreds of levees, whose integrity is in question, are in place in front of communities and properties with little realistic hope of funding for inspection, repair or upgrade," Galloway said.
Concern about the levees dates to the 1920s and 1930s, when killer floods on the Ohio and Mississippi rivers led Congress to order construction of more levees. Many were designed for the biggest flood likely to strike a particular area within 500 years or even 1,000 years.
Video: Hurricane Katrina: From the archives (on this page)
But starting in the late 1960s, federal policies have inadvertently encouraged the building of levees according to a less protective standard, the safety committee report said. One required financially strapped local governments to help cover levee building and maintenance costs.
Relatively low death tolls from major floods in recent decades also fed complacency that ended with Hurricanes Katrina and Rita, the report said. Together, they killed more than 1,800 people and caused $200 billion in damages, spurring calls for a nationwide levee inventory and upgrades.
The portion of the inventory developed thus far includes data on about 13,500 of the 14,700 miles of levees covered by the Army Corps' safety program. Data on the rest will be added by the end of the year, officials said. Many of the levees are operated and maintained by the Corps, or were built by the Corps and turned over to local officials.
John Paul Woodley Jr., who served as assistant secretary of the Army for public works during the George W. Bush administration, said the Corps has made good progress on the levee inventory but acknowledged "we're definitely behind where everybody had hoped we'd be."
? 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
I was in the grocery story last night in a rather long line behind someone you all know in the media ? Eleanor Clift.? We were talking and somehow got on the topic about our mutual love for pets?and she mentioned what a fellow member of the US media did while in Afghanistan covering the war.? I insisted she give me the name of the website (below).? As soon as I got the website (see below), I donated.? Of course I have a job and I know these are tough economic times, and I know there are many pet organizations here in the USA, but you might want to donate to this one.? It was created by an American and it is doing much for the pets in Afghanistan.?
If you all donated $10 or $20 or even $30, it would go far since there are so many of us.? If you can?t donate, I sure understand since I do know these are tough times for everyone.?
By the way, that black and white dog is named Sugar.
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Our Mission
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The Afghan Stray Animal League is a private non-profit organization in the U.S. that operates and supports a shelter and low-cost veterinary clinic for homeless, abandoned, sick or injured small animals in Afghanistan.The shelter is located in a refurbished house in Kabul, the Afghan capital, which has a large population of neglected street dogs and cats as well as thousands of backyard animals such as goats and donkeys whose owners cannot afford treatment for them.
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The shelter has been open full-time since the fall of 2004. It can comfortably house about 20 dogs and about 30 cats, and we have helped more than 400 animals so far. The shelter has a full-time Afghan staff including a veterinarian, an assistant veterinarian and manager. It has a fully stocked pharmacy and a small surgical clinic. The shelter staff accepts any animal that is brought to the door for help, including treatment of injuries, vaccinations, deworming, bathing and treatment of skin diseases. We have a car and driver to pick up any small animal that is injured, sick or found by someone who cannot bring it to the shelter.
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One of our major goals is to reduce the population of unwanted street animals. We offer both neutering and spaying of cats and dogs, in consultation with international veterinarians who visit the shelter or work with the national university veterinary school. No fees are charged for any services, although any foreign pet owners who come for vet care are asked for donations to cover the cost of vaccines and medicines. Our policy on euthanasia is that this should be used only as a last resort in the case of severe trauma or untreatable illness.
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Our primary mission is to care for needy small animals, restore them to health and find them loving homes. Most of those who adopt our animals are foreigners, and we are able to arrange to ship their rescued pets home if needed. We are also working to foster and encourage a culture of companion animal ownership in Afghanistan. The country has been devastated by war and poverty, and there is widespread neglect, abuse and fear of animals. We provide free dog houses, food, vaccines and other supplies to any Afghan who adopts a pet, and we conduct home visits to ensure the animal is being well treated. We also offer free talks at local non-profit children?s programs about the humane treatment of animals.
Forget relying solely on touch to control your Apple device. On future iPads, you may be able to control your tablet from across the room using 3D gestures, such as a swirl or swipe of the hand, if Apple's latest patent unearthing is anything to go by.
There is an increasing need for pharmacological tools for biomedical and translational research applications. The field of diversity-oriented synthesis (DOS) has been very fruitful in providing access to numerous new molecules with diverse shapes and chemical structures in order to discover candidate molecules for therapeutic use. Boston University researchers, in a paper published in the journal Nature Chemistry [23 OCTOBER 2011 | DOI: 10.1038/NCHEM.1178], present a new approach to accessing new, biorelevant structures by "remodelling" natural products. In this case, they demonstrate how the natural product derivative fumagillol can been remodelled to access a collection of new molecules using highly efficient chemical reactions.
"Overall, these studies should pave the way for work to identify pharmacological tools for use in CNS research, oncology, and as anti-infective agents," said John A. Porco, Jr., professor of chemistry at Boston University. "These studies also will enable future studies to remodel additional natural product scaffolds to access novel therapeutic agents."
In the search for novel biologically active molecules, DOS strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as useful starting points for DOS, wherein stereochemically rich core structures may be reorganized into chemotypes that are distinctly different from the parent structure. Ideally, to be suited to library applications, such transformations should be general and involve few steps.
With this objective in mind, Porco and colleagues including Professor John Snyder and postdoctoral fellow Dr. Brad Balthaser successfully remodelled the highly oxygenated natural product fumagillol in several ways using a reaction-discovery-based approach. In reactions with amines, excellent selectivity in a bis-epoxide opening/cyclization sequence was obtained using the appropriate metals catalysts forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles were further remodelled to other complex structures including novel benzoxazepines.
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Boston University Medical Center: http://www.bmc.org
Thanks to Boston University Medical Center for this article.
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You are what you eat: Low fat diet with fish oil slowed growth of human prostate cancer cellsPublic release date: 25-Oct-2011 [ | E-mail | Share ]
Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences
A low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed down the growth of prostate cancer cells -- the number of rapidly dividing cells -- in human prostate cancer tissue compared to a traditional, high-fat Western diet.
Done by researchers at UCLA's Jonsson Comprehensive Cancer Center, the short-term study also found that the men on the low-fat, fish oil supplement diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, though further studies are needed, said Dr. William Aronson, the study's first author and a researcher with UCLA's Jonsson Comprehensive Cancer Center.
The study also found that blood obtained from patients after the low-fat, fish oil diet program slowed the growth of prostate cancer cells in a test tube as compared to blood from men on the Western diet, which did not slow cancer growth.
"The finding that the low-fat, fish oil diet reduced the number of rapidly dividing cells in the prostate cancer tissue is important because the rate at which the cells are dividing can be predictive of future cancer progression," Aronson said. "The lower the rate of proliferation, the lesser the chances that the cancer will spread outside the prostate, where it is much harder to treat."
The study appeared Oct. 25, 2011 in Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research.
The study, which evaluated blood samples before and after the diet commenced and examined tissue from the removed prostate, validated previous studies by Aronson and others done on cell lines and in animal models. Aronson said the study using human blood and tissue also proved that the changes prompted by what the men were eating were clearly evident in their prostate tissue - the "treatment" was indeed reaching the targeted organ because of the changes in the prostate cell membrane's fatty acid composition.
"You truly are what you eat," said Aronson, a clinical professor of urology, who also serves as chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center. "Based on our animal studies, we were hopeful that we would see the same effects in humans. We are extremely pleased about our findings, which suggest that by altering the diet, we may favorable affect the biology of prostate cancer."
Aronson measured proliferation, or the rate of prostate cancer cell division, by staining tissue obtained from the radical prostatectomy specimens with an antibody against Ki-67, a protein involved in the cell-cycle progression and growth.
"The percentage of prostate cancer cells that stained for Ki-67 was determined by the pathologist, and this gave us an objective measurement of the percentage of cells that were actively dividing and therefore more aggressive," said Aronson. "Previous studies found that patients with higher levels of Ki-67 in their prostate cancer tissue were more likely to have their prostate cancer progress to advanced stages, and were more likely to die from their prostate cancer. Thus, we are extremely encouraged by our findings that a low-fat diet with fish oil lowered Ki-67 levels and may have the potential to slow the progression of prostate cancer."
Diet studies often are difficult to evaluate because getting patients to comply with dietary changes can be challenging. However, the food eaten by men in both arms of this study was precisely controlled, Aronson said. The meals were prepared by chefs in the UCLA Clinical Translational Research Center and delivered in bulk to study participants several times a week. Participants also met with a dietician, kept food diaries and were required to return uneaten food.
"The key to this study was having the meals prepared and delivered to the study participants," Aronson said. "This resulted in a very high rate of compliance, making the study very well controlled."
The Western diet consisted of 40 percent of calories from fat, generally equivalent to what many Americans consume today. The fat sources also were typical of the American diet, and included high levels of omega-6 fatty acids from corn oil and low levels of fish oil that provide omega-3 fatty acids.
The low-fat diet consisted of 15 percent of calories from fat. Additionally, the men on this diet took five grams of fish oil per day in five capsules, three with breakfast and two with dinner, to provide fish oil omega-3 fatty acids. Omega-3 fatty acids have been found to reduce the incidence of heart disease and fight inflammation, and inflammation has been associated with certain cancers.
"Preclinical studies suggest that lowering dietary omega-6 fatty acids from corn oil and increasing omega-3 fatty acids from fish oil decreases the risk of prostate cancer development and progression," the study states. "We found this diet intervention resulted in a decrease in omega-6 vs. omega-3 fatty acid ratios in benign and malignant prostate tissue and a decrease in malignant cell proliferation."
Aronson cautioned that he could not recommend dietary changes based on this study because of its short duration and small sample size. However, based on these results he is organizing a much larger study of 100 men with prostate cancers who have elected active surveillance, meaning they're not getting any treatment for their disease but are getting regular biopsies and check-ups.
The future study will randomly divide the men into a low-fat, fish oil supplement group and a traditional Western diet group and follow them for a year to evaluate the diet effects on prostate cancer proliferation.
###
This study was funded in part by the National Cancer Institute, the Veterans Administration and the Ruby Family Foundation.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
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You are what you eat: Low fat diet with fish oil slowed growth of human prostate cancer cellsPublic release date: 25-Oct-2011 [ | E-mail | Share ]
Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences
A low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed down the growth of prostate cancer cells -- the number of rapidly dividing cells -- in human prostate cancer tissue compared to a traditional, high-fat Western diet.
Done by researchers at UCLA's Jonsson Comprehensive Cancer Center, the short-term study also found that the men on the low-fat, fish oil supplement diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, though further studies are needed, said Dr. William Aronson, the study's first author and a researcher with UCLA's Jonsson Comprehensive Cancer Center.
The study also found that blood obtained from patients after the low-fat, fish oil diet program slowed the growth of prostate cancer cells in a test tube as compared to blood from men on the Western diet, which did not slow cancer growth.
"The finding that the low-fat, fish oil diet reduced the number of rapidly dividing cells in the prostate cancer tissue is important because the rate at which the cells are dividing can be predictive of future cancer progression," Aronson said. "The lower the rate of proliferation, the lesser the chances that the cancer will spread outside the prostate, where it is much harder to treat."
The study appeared Oct. 25, 2011 in Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research.
The study, which evaluated blood samples before and after the diet commenced and examined tissue from the removed prostate, validated previous studies by Aronson and others done on cell lines and in animal models. Aronson said the study using human blood and tissue also proved that the changes prompted by what the men were eating were clearly evident in their prostate tissue - the "treatment" was indeed reaching the targeted organ because of the changes in the prostate cell membrane's fatty acid composition.
"You truly are what you eat," said Aronson, a clinical professor of urology, who also serves as chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center. "Based on our animal studies, we were hopeful that we would see the same effects in humans. We are extremely pleased about our findings, which suggest that by altering the diet, we may favorable affect the biology of prostate cancer."
Aronson measured proliferation, or the rate of prostate cancer cell division, by staining tissue obtained from the radical prostatectomy specimens with an antibody against Ki-67, a protein involved in the cell-cycle progression and growth.
"The percentage of prostate cancer cells that stained for Ki-67 was determined by the pathologist, and this gave us an objective measurement of the percentage of cells that were actively dividing and therefore more aggressive," said Aronson. "Previous studies found that patients with higher levels of Ki-67 in their prostate cancer tissue were more likely to have their prostate cancer progress to advanced stages, and were more likely to die from their prostate cancer. Thus, we are extremely encouraged by our findings that a low-fat diet with fish oil lowered Ki-67 levels and may have the potential to slow the progression of prostate cancer."
Diet studies often are difficult to evaluate because getting patients to comply with dietary changes can be challenging. However, the food eaten by men in both arms of this study was precisely controlled, Aronson said. The meals were prepared by chefs in the UCLA Clinical Translational Research Center and delivered in bulk to study participants several times a week. Participants also met with a dietician, kept food diaries and were required to return uneaten food.
"The key to this study was having the meals prepared and delivered to the study participants," Aronson said. "This resulted in a very high rate of compliance, making the study very well controlled."
The Western diet consisted of 40 percent of calories from fat, generally equivalent to what many Americans consume today. The fat sources also were typical of the American diet, and included high levels of omega-6 fatty acids from corn oil and low levels of fish oil that provide omega-3 fatty acids.
The low-fat diet consisted of 15 percent of calories from fat. Additionally, the men on this diet took five grams of fish oil per day in five capsules, three with breakfast and two with dinner, to provide fish oil omega-3 fatty acids. Omega-3 fatty acids have been found to reduce the incidence of heart disease and fight inflammation, and inflammation has been associated with certain cancers.
"Preclinical studies suggest that lowering dietary omega-6 fatty acids from corn oil and increasing omega-3 fatty acids from fish oil decreases the risk of prostate cancer development and progression," the study states. "We found this diet intervention resulted in a decrease in omega-6 vs. omega-3 fatty acid ratios in benign and malignant prostate tissue and a decrease in malignant cell proliferation."
Aronson cautioned that he could not recommend dietary changes based on this study because of its short duration and small sample size. However, based on these results he is organizing a much larger study of 100 men with prostate cancers who have elected active surveillance, meaning they're not getting any treatment for their disease but are getting regular biopsies and check-ups.
The future study will randomly divide the men into a low-fat, fish oil supplement group and a traditional Western diet group and follow them for a year to evaluate the diet effects on prostate cancer proliferation.
###
This study was funded in part by the National Cancer Institute, the Veterans Administration and the Ruby Family Foundation.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
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LOS ANGELES ? Prosecutors concluded their case Monday against the doctor charged with Michael Jackson's death after questioning 33 witnesses, including an expert who said the physician committed numerous violations of medical practices that could have led to the singer's serious injury or death.
Defense attorneys quickly called their first witness ? Dona Norris, a records custodian for the Beverly Hills Police Department who discussed the 911 call received on the day Jackson died.
She was one of 15 defense witnesses expected over the next few days.
The final prosecution witness against defendant Dr. Conrad Murray was Dr. Steven Shafer, an expert on the anesthetic propofol that authorities say killed Jackson.
Shafer told jurors that it's difficult to know the precise effects of the drug on the singer because he had been given so much of it in the months before he died.
Shafer made the statement while being cross-examined by lead defense attorney Ed Chernoff, who noted the risk that Jackson would stop breathing should have been low after the first few minutes the drug was administered on the day he died.
Chernoff based that conclusion on models and research done by Shafer.
"In Mr. Jackson's case, it's harder to have that certainty," Shafer replied. "There's very little, almost no precedent for this level of propofol exposure."
Shafer, a Columbia University researcher and professor, said Jackson had been receiving propofol almost every night for more than two months, according to a police statement by Murray. The Houston-based cardiologist has pleaded not guilty to involuntary manslaughter.
Shafer previously testified that he thinks a propofol overdose killed Jackson. But he said Murray kept no records about how much of the drug he gave the singer.
Shafer has said the only possible explanation for Jackson's death based on the evidence was that Murray put the singer on an IV drip of propofol then left the room after the singer appeared to be asleep.
Murray's attorneys will try to counter four weeks of damaging testimony from prosecution witnesses who have cast Murray as an inept, distracted and opportunistic doctor who repeatedly broke legal, ethical and professional guidelines.
Murray's attorneys have not publicly revealed whether they will call him to testify.
Jurors have heard from the doctor through a more than two-hour interview with police, and it seems unlikely his attorneys would subject their client to what would be blistering questioning from prosecutors.
Shafer has not retreated from his position that Murray is solely responsible for Jackson's death and that the cardiologist committed 17 egregious violations of medical practices that each could have either led to Jackson's serious injury or death.
Out of sight of the jury, the defense's theory has shifted in recent months from arguing that Jackson swallowed propofol and gave himself the fatal dose and more recently that the singer had swallowed several pills of the sedative lorazepam, which led to his death.
They might also argue that Jackson somehow gave himself a shot of propofol after Murray left the room, killing him quickly.
___
AP Special Correspondent Linda Deutsch contributed to this report.
___
McCartney can be reached at http://twitter.com/mccartneyAP
ERCIS, Turkey (Reuters) ? More than 200 people were confirmed killed and hundreds more feared dead after an earthquake hit parts of southeast Turkey Sunday with rescue teams working through the night to free trapped survivors.
Early Monday Interior Minister Idris Naim Sahin said the 7.2 magnitude quake killed 100 in the city of Van and 117 in the badly hit town of Ercis, 100 km (60 miles) further north. The death toll was expected to rise.
Overseeing emergency operations in Ercis, Sahin said a total of 1,090 people were known to have been injured. Hundreds remain unaccounted for.
Rescue efforts struggled to get into full swing following the quake, with electricity cut off as darkness fell on the towns and villages on the barren Anatolian steppe near the border with Iran.
Survivors and emergency service workers searched frantically through broken concrete, using hands, shovels and torches or working under floodlights powered by mobile generators.
Prime Minister Tayyip Erdogan said there were an unknown number of people unaccounted for under the collapsed buildings of the stricken towns, and he feared the worst for villagers living in outlying rural areas, who had still to be reached.
"Because the buildings are made of adobe, they are more vulnerable to quakes. I must say that almost all buildings in such villages are destroyed," Erdogan told a televised news conference in Van shortly after midnight Sunday.
Scores of strong aftershocks have jolted the region in the hours since the quake struck at 6:41 a.m. EDT Sunday.
"BE PATIENT"
In Van, a bustling and ancient city on a lake ringed by snow-capped mountains and with a population of 1 million, cranes shifted rubble off a crumpled six-storey apartment block where bystanders said 70 people were trapped.
Erdogan visited Ercis earlier by helicopter to assess first hand the scale of the disaster. With 55 buildings flattened, including a student dormitory, the level of destruction in Ercis, a town of 100,000, was greater than in Van, where fewer came down.
"We don't know how many people are in the ruins of collapsed buildings, it would be wrong to give a number," he said.
Reuters television images from Ercis showed rescuers trying to clam one young boy, aged about 10, pinned beneath a concrete slab.
"Be patient, be patient," they pleaded as the boy whimpered. The lifeless hand of an adult, with a wedding ring, was visible just a few centimeters (inches) in front of his face.
The military issued a statement saying two battalions had been sent to assist the relief operations.
Soldiers were deployed in the town to help rescuers and digging machines had also arrived to help. There was a constant wail of ambulance sirens ferrying the injured to hospitals.
Dogan news agency reported that 24 people were pulled from the rubble alive in the two hours after midnight.
Reuters photographer Osman Orsal earlier described seeing dead body after body being pulled from the debris.
"Ambulances, soldiers, emergency teams everywhere now, working on getting people out of collapsed buildings. I have seen many dead bodies being taken out, the teams are trying to find people alive," Orsal said.
One nurse told CNN Turk news channel the town's hospital was so badly damaged that staff were treating injured in the garden, and bodies were being left outside the building,
After visiting the quake zone, Erdogan returned to Ankara, where he is expected to chair a cabinet meeting to discuss the response to the disaster.
He said Turkey was able to meet the challenge itself, but thanked countries that had offered help, including Armenia and Israel, two governments that have strained relations with Ankara.
In Van province officials scrambled to provide shelter for people rendered homeless or too afraid to go home while the aftershocks continued with alarming regularity.
"We are working on supplying people with places to spend the night, find shelter. One hundred tents are being erected in the city stadium now, and 700 more will be put up in the municipality stadium," Sahin told Reuters in Ercis.
(Writing by Simon Cameron-Moore; Editing by Matthew Jones)
On the nanoscale, particles flow in unexpected waysPublic release date: 24-Oct-2011 [ | E-mail | Share ]
Contact: Charles E. Blue cblue@aip.org 301-209-3091 American Institute of Physics
Researchers studying how fluids travel through nanoscale channels were surprised to discover that the fluids don't flow equally well in all directions. Contrary to the behavior in the macroscale world, the researchers discovered that methyl alcohol, when it was placed in a network of nanoscale channels in a mineral known as a zeolite, diffused 1,000 times faster in one direction than another. This is the first known evidence of such highly unequal diffusion of molecules in a nanoporous material. This highly lopsided flow occurred despite the fact that the diameters of the respective channels are quite similar. In the mineral, two types of nanoscale channels are present: 8-ring and 10-ring channels. The numbers refers to the relative size of the pores in the material, though they are extremely close in size with only subtle differences in geometry. The methyl alcohol molecules were stored initially inside an optical cell.
At the beginning of the experiment, the pressure in the surrounding atmosphere is increased instantaneously and kept constant for the rest of the experiment. The methanol molecules then enter the zeolite voluntarily since they naturally prefer to be in the zeolite than in the gas phase. Once inside the mineral, the researchers measured the particle concentration at various points along the pores. From these profiles, they were able to calculate the particle flux (number of particles that cross a certain area in a certain time) and observed the highly biased flow.
Earlier research reported that the diffusivity of a guest molecule inside a pore network is extremely sensitive to the ratio of the pore window and molecule diameter, particularly if both quantities are close to each other, as was the case with the zeolite channels and the methyl alcohol atoms. The researchers in this study speculate that since the 8-ring window is slightly smaller than the 10-ring window, a smaller diffusivity (and therefore a smaller flux) might be expected. Another reason might be the different pore geometry (straight in the case of the 10-ring channels versus windows and cavities in the 8-ring channels).
Presented in the AIP's Journal of Chemical Physics, this apparently counterintuitive discovery has far-reaching implications for the understanding, development, and exploitation of novel microscopic materials, including nanotubes and "intelligent" cell membranes for purposeful drug delivery, the functionality of which is based on an extreme direction dependence of molecular mobilities.
###
Article: "Micro-imaging of transient guest profiles in nano-channels" is accepted for publication in the Journal of Chemical Physics.
Authors: F. Hibbe (1), V.R.R. Marthala (2), C. Chmelik (1), J. Weitkamp (2), and J. Krger (1).
(1) Faculty of Physics and Earth Sciences, University of Leipzig, Germany
(2) Institute of Chemical Technology, University of Stuttgart, Germany
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
On the nanoscale, particles flow in unexpected waysPublic release date: 24-Oct-2011 [ | E-mail | Share ]
Contact: Charles E. Blue cblue@aip.org 301-209-3091 American Institute of Physics
Researchers studying how fluids travel through nanoscale channels were surprised to discover that the fluids don't flow equally well in all directions. Contrary to the behavior in the macroscale world, the researchers discovered that methyl alcohol, when it was placed in a network of nanoscale channels in a mineral known as a zeolite, diffused 1,000 times faster in one direction than another. This is the first known evidence of such highly unequal diffusion of molecules in a nanoporous material. This highly lopsided flow occurred despite the fact that the diameters of the respective channels are quite similar. In the mineral, two types of nanoscale channels are present: 8-ring and 10-ring channels. The numbers refers to the relative size of the pores in the material, though they are extremely close in size with only subtle differences in geometry. The methyl alcohol molecules were stored initially inside an optical cell.
At the beginning of the experiment, the pressure in the surrounding atmosphere is increased instantaneously and kept constant for the rest of the experiment. The methanol molecules then enter the zeolite voluntarily since they naturally prefer to be in the zeolite than in the gas phase. Once inside the mineral, the researchers measured the particle concentration at various points along the pores. From these profiles, they were able to calculate the particle flux (number of particles that cross a certain area in a certain time) and observed the highly biased flow.
Earlier research reported that the diffusivity of a guest molecule inside a pore network is extremely sensitive to the ratio of the pore window and molecule diameter, particularly if both quantities are close to each other, as was the case with the zeolite channels and the methyl alcohol atoms. The researchers in this study speculate that since the 8-ring window is slightly smaller than the 10-ring window, a smaller diffusivity (and therefore a smaller flux) might be expected. Another reason might be the different pore geometry (straight in the case of the 10-ring channels versus windows and cavities in the 8-ring channels).
Presented in the AIP's Journal of Chemical Physics, this apparently counterintuitive discovery has far-reaching implications for the understanding, development, and exploitation of novel microscopic materials, including nanotubes and "intelligent" cell membranes for purposeful drug delivery, the functionality of which is based on an extreme direction dependence of molecular mobilities.
###
Article: "Micro-imaging of transient guest profiles in nano-channels" is accepted for publication in the Journal of Chemical Physics.
Authors: F. Hibbe (1), V.R.R. Marthala (2), C. Chmelik (1), J. Weitkamp (2), and J. Krger (1).
(1) Faculty of Physics and Earth Sciences, University of Leipzig, Germany
(2) Institute of Chemical Technology, University of Stuttgart, Germany
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