The special and sexy talent of Amy G

Amy G shows us her very special talent, with her panties down!

The Waldo Ultimatum - The Imponderables

Nominated for Best Web Clip in the 2008 Canadian Comedy Awards. Vote for this clip here: http://ccavoting.com/register.php
Brought to you by the incredibly talented sketch group, The Imponderables: http://theimponderables.com

See more hilarious videos on http://www.justforlaughs.com

Some Funny Puns!

1. The roundest knight at king Arthur's round table was Sir Cumference. He acquired his size from too much pi.

2. I thought I saw an eye doctor on an Alaskan island, turned out he was an optical Aleutian.

3. She was only a whisky maker, but he loved her still.

4. A rubber band pistol was confiscated from algebra class because it was a weapon of math disruption.

5. The butcher backed into the meat grinder and got a little behind in his work.

6. No matter how much you push the envelope, it'll still be stationery.

7. A dog gave birth to puppies near the road and was cited for littering.

8. A grenade thrown into a kitchen in France would result in Linoleum Blownapart.

9. Two silk worms had a race. They ended up in a tie.

10. Time flies like an arrow. Fruit flies like a banana.

11. A hole has been found in the nudist camp wall. The police are looking into it.

12. Atheism is a non-prophet organization.

13. Two hats were hanging on a hat rack in the hallway. One hat said to the other, 'You stay here, I'll go on a-head.'

14. I wondered why the baseball kept getting bigger. Then it hit me.

15. A sign on the lawn at a drug rehab center said: 'Keep off the Grass.'

16. A small boy swallowed some coins and was taken to a hospital. When his grandmother telephoned to ask how he was,
a nurse said, 'No change yet.'

17. A chicken crossing the road is poultry in motion.

18. It's not that the man did not know how to juggle, he just didn't have the balls to do it.

19. The short fortune-teller who escaped from prison was a small medium, at large.

20. The man who survived mustard gas and pepper spray is now a seasoned veteran.

21. A backward poet writes in-verse.

22. In democracy it's your vote that counts. In feudalism it's your count that votes.

23. When cannibals ate a missionary, they got a taste of religion.

24. Don't join dangerous cults: Practice safe sects!

The Psychology of Saving More

Financial planners often suggest clients figure out how much they'll need to retire and save toward that huge number. Utpal "Paul" Dholakia, associate professor of management at Houston's Rice University, thinks people would do better to think about how much they'll save next month. A paper he co-wrote with Leona Tam of Old Dominion University found that those who planned savings for the next month did far better than those who tried to plan further out. In one experiment, people said they'd save an average $287 next month but saved $440. When asked to plan ahead four months, they said they'd save an average $946, but put aside just $123. Amy Feldman spoke with Dholakia.

Did the results surprise you? We were shocked. How can someone tell you they will save $1,000 and then only save $100? It's a gross misprediction of behavior.

So we're better off trying to save for next month than next year? That's it. Don't plan in advance because it makes you overoptimistic. You think: "I might get a windfall or a raise." And not only do people who give a savings estimate for four months from now estimate too high but they become more risk-seeking.

Is this just an American problem? We're working with colleagues in China and Korea to see if this translates. In Korea, the young are Westernized, so we think [their behavior] will look like that of Americans.

-Edited by Suzanne Woolley

Clearing the confusion: Obama vs. Palin

I'm a little confused. Let me see if I have this straight...

* If you grow up in Hawaii, raised by your grandparents, you're
"exotic, different."

* Grow up in Alaska eating moose burgers, a quintessential American
story.

* If your name is Barack you're a radical, unpatriotic Muslim.

* Name your kids Willow, Trig and Track, you're a maverick.

* Graduate from Harvard law School and you are unstable.

* Attend 5 different small colleges before graduating, you're well
grounded.

* If you spend 3 years as a brilliant community organizer, become the
first black President of the Harvard Law Review, create a voter
registration drive that registers 150,000 new voters, spend 12 years
as a Constitutional Law professor, spend 8 years as a State Senator
representing a district with over 750,000 people, become chairman of
the state Senate's Health and Human Services committee, spend 4 years
in the United States Senate representing a state of 13 million people
while sponsoring 131 bills and serving on the Foreign Affairs,
Environment and Public Works and Veteran's Affairs committees, you
don't have any real leadership experience.

* If your total resume is: local weather girl, 4 years on the city
council and 6 years as the mayor of a town with less than 7,000
people, 20 months as the governor of a state with only 650,000 people,
then you're qualified to become the country's second highest ranking
executive.

* If you have been married to the same woman for 19 years while
raising 2 beautiful daughters, all within Protestant churches, you're
not a real Christian.

* If you cheated on your first wife with a rich heiress, and left your
disfigured wife and married the heiress the next month, you're a
Christian.

* If you teach responsible, age appropriate sex education, including
the proper use of birth control, you are eroding the fiber of society.

* If, while governor, you staunchly advocate abstinence only, with no
other option in sex education in your state's school system while your
unwed teen daughter ends up pregnant, you're very responsible.

* If your wife is a Harvard graduate lawyer who gave up a position in
a prestigious law firm to work for the betterment of her inner city
community, then gave that up to raise a family, your family's values
don't represent America's.

* If you're husband is nicknamed "First Dude", with at least one DWI
conviction and no college education, who didn't register to vote until
age 25 and once was a member of a group that advocated the secession
of Alaska from the USA, your family is extremely admirable.

OK, much clearer now.

Sylvester Stallone Doing Rambo 5 And 6 And Hopefully No More

By Stuart Heritage

This year’s Rambo gave the world just what it needed - an unnaturally jacked-up sexagenarian doing gory murder on millions of foreigners.

And, make no mistake, Rambo worked on every conceivable level - as a flat-out action movie, as a piece of issue-based social filmmaking, as a way of utterly obliterating the Burmese tourist industry, as a warning against the use of HGH at an advanced age, as a reminder that nobody looks good with a mullet. We could go on.

But anyway, that’s why we’re thrilled at the news that Sylvester Stallone has just signed on to direct Rambo 5, due to start filming next year. What’s more, Sylvester Stallone is also thought to be writing Rambo 6. Plus Stallone wants Rambo 7 to be an animated cartoon, and Rambo 8 to be a musical, and Rambo 9 to be a stageplay and Rambo 10 to be a remake of Rambo 6 starring children and puppets and Rambo 11 to be an avant-garde Warhol-style close-up of one of his own eyelashes that lasts for 48 hours.

All true. Except for the last 57 words.

Though easy to mock at the time, when Sylvester Stallone revisited one of his most famous cinematic creations for Rocky Balboa, he crafted an elegant, eloquent finale to the series that dropped the overblown posturing of its previous sequels and let the character go with a respect and dignity that nobody really thought possible.

And, right after that, Sylvester Stallone made another Rambo movie, about an old bloke killing everything and running around going “Aaargh!” a lot. So it all balances out.

And, unquestionably, Rambo was a success. It made money. It regained Sylvester Stallone’s position as the daddy of the gormless action movie. It reminded Americans that diplomacy never works and the only to resolve international disputes is to send a mental old pensioner into the woods to tear out peoples’ throats and shred them to pieces with a minigun.

That’s why it’s nothing short of genius that Sylvester Stallone has just signed up to make Rambo 5, while simultaneously writing Rambo 6. Moviehole reports:

The aging action-hero has already written “Rambo 5” – rumoured to be shooting next year in Bulgaria, though set in the United States - and is about to put pen to paper on a sixth installment of the series. Also, the next two films won’t be War films like the original movies… but just straight-up action thrillers.

That’s awesome news - when it comes to near-silent beefcakes mumbling something vaguely philosophical before firing 600 arrows through a guerrilla’s face, nobody does it better than Sylvester Stallone. But let’s not get too ahead of ourselves here - we still have our reservations about Rambo 5 and Rambo 6. For instance:

*Action thrillers? That sounds terrible. Scooby Doo is an action thriller. If Rambo 5 is about Sylvester Stallone investigating a haunted funfair we’re going to be deeply pissed off.

*To make Rambo 5 better than Rambo 4, Stallone clearly needs to up the body count. We’re not sure that’s even physically possible, to be honest, unless the whole film is just a fast-forwarded domino line of shifty-looking south east Asian men getting their faces blown off one after another for a full day.

*If Rambo 5 starts filming next year, Sylvester Stallone will be 63, so he could feasibly be in his late sixties by the time Rambo 6 rolls around. Let’s hope that Sylvester Stallone has already factored that into the script and made sure that Rambo’s biggest enemies in that film are incontinence and an inability to eat soup properly.

*Remember that Sylvester Stallone needed vast quantities of Human Growth Hormone to keep him in shape for Rambo 4. We wouldn’t be surprised if, for Rambo 6, Stallone has to resort to drinking babies’ spinal fluid and injecting himself with unicorn semen.

Other than all that, though, great. We can’t wait.

19 Child Actors Who Went on to Respectable Careers

By Donna Bowman, Amelie Gillette, Sean O'Neal, Keith Phipps, Leonard Pierce, Tasha Robinson, Claire Zulkey
September 15th, 2008

1. Jackie Coogan

As the original kid star (literally: He captured audiences' hearts as the titular sidekick in Charlie Chaplin's The Kid), Coogan was also the first Hollywood actor to become an industry through heavy merchandising. His signature pageboy haircut and droopy overalls adorned everything from dolls to peanut-butter jars to toy whistles in the early 1920s, generating millions of dollars in income before Coogan even hit puberty. Unfortunately, his mother and stepfather blew through it to support heroin and cocaine habits, leaving him nearly penniless. He wasn't successful in taking them to court, but California did institute the still-active Child Actor's Bill, or Coogan Bill, in his honor, protecting the rights of child stars for decades to come. Robbed of early retirement in his teens, Coogan remained in show business until his death at age 69; after a stint in World War II, he even landed a second iconic role (and arguably his most famous today) as Uncle Fester on The Addams Family, whereupon he once again found his face—albeit one nearly unrecognizable under pounds of makeup—plastered across the cultural landscape.

2. Dean Stockwell

Dean Stockwell has so firmly established himself as an aging character actor with a line in playing worldly, wise smart-asses who know more than they're telling that it's odd to think he was ever even a young man, let alone a child star. But Stockwell had a dozen movies under his belt before he was a dozen years old. Before he was 14, he'd played the son of Nick and Nora Charles, the lead role in Rudyard Kipling's Kim, and the titular weirdo in The Boy With Green Hair. And as odd as it may seem for fans of his sex-crazed, cynical Cylon in Battlestar Galactica to think of him as the cherubic youth from Anchors Aweigh, imagine how people who grew up watching him in Gentleman's Agreement must have felt when they saw him crooning "In Dreams" to a maniacal Frank Booth in Blue Velvet.

3. Drew Barrymore

Drew Barrymore, it can fairly be said, was born to be a star. At one point the darling of an acting dynasty that produced Hollywood legends like John, Ethel, and Lionel Barrymore, she got her first screen role when she was less than a year old, and by the time she was 10, she'd already appeared in Altered States, with star-making turns in Firestarter and E.T.: The Extra-Terrestrial. Unfortunately, she proved equally precocious at movie-star temptations: She started using drugs when she was 9, and checked herself into rehab at 13. Now that's determination! Since her adult comeback, she hasn't always chosen the best roles—her, uh, biggest moneymaking parts were in the Charlie's Angels remakes—but she's at least showed an interest in stretching, as witnessed by appealing turns in Donnie Darko, Confessions Of A Dangerous Mind, and Music And Lyrics.

4. Christian Bale

Many of Christian Bale's memorable youthful roles—Jim Hawkins in a TV-movie adaptation of Robert Louis Stevenson's Treasure Island, his turn as Cowboy Kelly in the inexplicably beloved Disney musical Newsies, his tweener turns in Swing Kids and Little Women—were built on the part that made him a young star: His impressive performance as Jamie Graham, the stand-in for J.G. Ballard in Steven Spielberg's hit-and-miss adaptation of Empire Of The Sun. Only 11 years old when he got the part, and barely 13 when it was released, Bale inhabited the role—only his second big-screen part—as if he'd been acting for decades. Nowadays, Bale has gone on to mega-stardom playing Bruce Wayne in Christopher Nolan's Batman movies, but unlike many child stars, he's never really had any downtime in his transition from child star to adult draw; he's basically been constantly in front of a camera since he was 12.

5. Jodie Foster

Even since her childhood acting days, Jodie Foster maintained a certain dignity that helped her transition from youngster to adult performer without much visible difficulty. Even when she was performing in Disney kid fare such as Freaky Friday, she had a sort of no-nonsense cool that indicated she, like her characters, was already inclined more toward maturity than cuteness. It probably helped that her breakout role at age 14, as an underage prostitute in 1976's Taxi Driver, left very little room for adorability. Since then, an Ivy-League education, a grounded and fiercely-guarded private life, plus good fortune with roles (Oscars for The Accused and Silence Of The Lambs—even Bugsy Malone, one of her kid roles, is a classic) kept her on a track that no one, not even John Hinckley, could distract her from.

6. Natalie Wood

Natalie Wood was acting by age 4, and before she turned sweet 16, she had 20 credits to her name, including a classic role in Miracle On 34th Street and a pivotal turn in The Searchers. When she appeared as James Dean's love interest in Rebel Without A Cause, a performance that earned her an Academy Award nomination for Best Supporting Actress, she marked the transition from child star to all-grown-up actress, and she never looked back. Before her untimely death at age 43, she received two more nominations and appeared in hits and critics' darlings: West Side Story, Splendor In The Grass, The Great Race, Bob & Carol & Ted & Alice. Her string of turkeys in adulthood earned her a Worst Actress Of The Year award from the Harvard Lampoon in 1966; she had the good grace to show up and accept the award in person, surely proof that not all child actors grow up to be spoiled brats.

7. Mickey Rooney

Nobody defines "child star" as thoroughly as Rooney, a tot who entered moviemaking at age 5 as the star of a series of one-reelers. He was a boyish 16 when he was cast in A Family Affair, the first of 14 Andy Hardy movies released in the next nine years. At the same time, he started his longtime collaboration with Judy Garland, and just a year later, he played his first dramatic role, in Boys Town. Although he continued working in television after the war, it wasn't until he became a dwarfish father figure that he returned to popular and critical acclaim, playing wise old coots in films like Requiem For A HeavyweightandThe Black Stallion. As for his yellowface role as Holly Golightly's screechy Japanese neighbor in Breakfast At Tiffany's, we'll just note that the broad ethnic stereotype might have fit his comedic talents, but it certainly wasn't all his idea.

8. Seth Green

Not every child actor gets to jump straight into a John Irving adaptation (The Hotel New Hampshire, 1984) with Jodie Foster. And it didn't exactly happen to Seth Green, who at age 10 appeared in the now-forgotten wacky comedy Billions For Boris,which was released the same year. But Green always managed to land on his feet when bouncing from TV commercials to prestige films like Woody Allen's Radio Days, in which he played a 13-year-old stand-in for Allen's own childhood self. Green segued smoothly from child actor to teenage wisecracker in Buffy The Vampire Slayerand the Austin Powers series, then without missing a beat, reinvented himself as a self-aware adult star (Josie And The Pussycats, The Italian Job) and an auteur (Robot Chicken). It's no accident that he's always seemed smart and in full control of his persona, even as a kid; that impression makes him easy for postmodern viewers to love.

9. Kirsten Dunst

In Interview With The Vampire, Kirsten Dunst played a child vampire, a role that required her to project world-weary experience and frustration through the prism of youth. Not an easy task for an 11-year-old. But Dunst pulled it off, becoming the most memorable vampire in a movie full of them, and not just because of her famous snaggletooth smile. Since then, Dunst has made a career out of balancing roles both light and heavy, straightforward and strange. She can be an excellent comic actress (Dick, or Bring It On), as well as an effectively moving one (The Virgin Suicides). For every misstep (Wimbledon) or turn as Spider-Man's love interest, there's an Eternal Sunshine Of The Spotless Mind. On paper (or the IMDB), her career almost looks schizophrenic, but it's better to be the actress who's allowed to be all over the place than the one stuck in romantic-comedy purgatory. (Hi, Kate Hudson!)

10. Christina Ricci

Christina Ricci got her start playing Cher's daughter in Mermaids, but she's best known for playing creepy/cute Wednesday Addams in the Addams Family movies (and MC Hammer video). That "creepy/cute" quality has informed most of Ricci's best roles, like her turn in The Opposite Of Sex as a cynical, sharp teen con artist. There's a kind of spacey-ness to Ricci's looks—wide, far-set eyes, round kewpie-doll face, large forehead—that can either be dialed up for maximum creepiness (The Ice Storm, Pumpkin) or dialed down until she appears almost child-like and vulnerable (as the girlfriend of a serial killer in Monster, or as a fairy-tale heroine in Sleepy Hollow and Penelope). Dark, yes. Cartoonish, yes. But Ricci could never play conventional.

11. Roddy McDowall

World War II sent young Roddy McDowall to America, where he achieved stardom almost immediately as the lead in John Ford's How Green Was My Valley, a fond-but-unsparing tale of growing up poor and Welsh. From there, he had a couple of high-profile roles working with animals in Lassie Come Home and in My Friend Flicka and its sequel. After sticking largely to television in the '50s, McDowall worked steadily as a character actor up to his death in 1998. Always fragile and boyish in appearance and politely eccentric in demeanor, he worked especially well in black comedies like The Loved One, Lord Love A Duck, Pretty Maids All In A Row, and the smart '80s horror movie Fright Night, a late-career highlight. His most iconic adult role, however, found him hiding his face behind ape makeup as Dr. Cornelius in The Planet Of The Apes.

12. Ron Howard

After growing up in everyone's living room as Opie on The Andy Griffith Show, Ron Howard enjoyed a second act as a young actor thanks to Happy Days. Then he shifted gears for a third act as a highly successful director and producer, first by directing himself in the Roger Corman-produced Grand Theft Auto, then by helming a series of hits that began with Night Shift and have carried on through The Da Vinci Code.

13. Jason Bateman

Howard also memorably provided the narration for Arrested Development, a show starring another former child actor, Jason Bateman. Bateman never really disappeared from acting, working through a fallow period post-child-stardom in the '80s, which found him working onLittle House On The Prairie, Silver Spoons, and The Hogan Family. In the years between, Bateman appeared on one non-starter series after another, but he must have been honing the dry delivery that made him the perfect straight man in Arrested Development, skills he's since brought to work in films like Hancockand Juno.

14. Robert Blake

Young Mickey Gubitosi joined the cast of the Our Gang short series in 1939 when he replaced Eugene "Porky" Lee. It was a time of transition, as the series moved from Hal Roach's studios to MGM. Breakout star Alfalfa soon left, and the quality of the shorts dropped until MGM pulled the plug in 1944. Gubitosi stuck with it, becoming Bobby Blake along the way. Our Gang led the way to parts in Red Ryder Westerns and a memorable, but uncredited, role in The Treasure Of The Sierra Madre. After a stint in the army, Blake began to rebuild his acting career, cementing his stardom in 1967 as one of the killers in In Cold Blood. Then he, um, lived happily ever after.

15. Joaquin Phoenix

The middle child of the Phoenix clan, Joaquin Phoenix had his first TV role at age 8, appearing in a single episode of Seven Brides For Seven Brothers, alongside his older brother River. (That show was River Phoenix's debut as well; he'd just turned 12 when the first of his 21 episodes aired.) River became famous faster, picking up increasingly visible roles in Explorers, Stand By Me, The Mosquito Coast, My Own Private Idaho, and more, while their sisters Rain and Summer had lower-profile careers, and Liberty Phoenix limited her show-biz career to two TV outings. (One was that same Seven Brides episode that introduced Joaquin.) But while River died young, victim of a drug overdose, Joaquin toiled in the trenches, with TV appearances on the likes of Murder, She Wrote, Hill Street Blues, The Fall Guy, and Alfred Hitchcock Presents. Acting under the name Leaf Phoenix—reportedly inspired by his more nature-named siblings—he gradually worked his way up to larger roles, first in the likes of SpaceCamp and Parenthood (where he played the miserable, furtively masturbating son of Diane Wiest), and then in more adult roles, in To Die For, Quills, and Gladiator. By the time of the M. Night Shyamalan films Signs and The Village, he already had a reputation as a deeply committed, serious adult actor, and his Oscar-nominated lead role in Walk The Line just sealed that rep.

16. Elijah Wood

It may be hard to think of Elijah Wood as an adult actor, considering his signature role as digitally tiny-fied, childlike hobbit Frodo Baggins in Peter Jackson's Lord Of The Rings movies. In the first of those films, at age 20, he doesn't look much bigger than he was when he got his start at age 8 in Internal Affairs, or the older of two abused brothers in the underrated Radio Flyer. Still, while he's spent years playing Frodo, he's made time for a small number of well-chosen, memorable adult rules, including the playing-against-type serial killer in Sin City, the lovelorn Patrick in Eternal Sunshine Of The Spotless Mind, and author Jonathan Safran Foer in the weird, unloved, but striking book adaptation Everything Is Illuminated.

17. Anna Paquin

Given that she'll always be remembered as the girl who won an Oscar at age 11 (though she still isn't the youngest Oscar winner), it's sometimes a little strange to see Anna Paquin all grown up—and sexified up—in the likes of 25th Hour or the new HBO series True Blood. As with many child stars, it may be tempting to think of her as two people—one, the cute little girl from The Piano and Fly Away Home, and the other, the cynical man-manipulator of The Squid And The Whale.

18. Natalie Portman

The same could be said of Natalie Portman, though she contains such multitudes that a simple dichotomy doesn't work. Is she the threatened little girl from Luc Besson's The Professional? (It was her feature debut; she was 12.) The remote, heavily costumed princess-slash-action-heroine of The Phantom Menace and its sequels? The sexy, slightly trampy, ignorant but determined power-player in Closer? The irritating Manic Pixie Dream Girl of Garden State? The abused victim of V For Vendetta and Goya's Ghosts? The domineering bitch-queen of The Other Boleyn Girl? Does her starring role in Mr. Magorium's Wonder Emporium explain anything? Portman is another actor who effectively grew up onscreen, but even watching her develop up close year after year since her childhood hasn't made it any easier to predict how good she'll be in a given role, or how good the film around her will be. Still, she's usually an arresting presence, if she gets material worth working with.

19. Elizabeth Taylor

McDowall's lifelong friend Elizabeth Taylor enjoyed an even smoother transition to adult roles. After breaking out at the age of 12 in National Velvet, she inched into grown-up parts incrementally, co-starring in Life With Father at 15, Little Women at 17, and playing a young bride at the age of 18 in 1950's Father Of The Bride. That hit doubled as a coming-out party, and Taylor spent the '50s and '60s as an international star, thanks to films like A Place In The Sun, Cat On A Hot Tin Roof, and Who's Afraid Of Virginia Woolf?, which paired her with her most famous on- and offscreen partner, Richard Burton. By the '70s, however, her most iconic roles were behind her. Growing up onscreen was easy. Growing old onscreen wasn't.

Cigar Aficionado Interviews Rocky Patel

Rocky Patel, 47, has quickly become one of the best-known faces in the world of premium cigars. The owner of Rocky Patel Premium Cigars Inc. spends most of his life on the road, either in the factories in Honduras and Nicaragua that make his cigars, in the tobacco fields of Central America or in the many cigar shops that sell his wares.

Recently, his 10th Anniversary smoke, the Rocky Patel Decade Torpedo, was rated a classic, scoring 95 out of 100 points in Cigar Insider and Cigar Aficionado tastings. In April, Patel sat down with senior editor David Savona to speak about the impact of that rating, the impressive growth of his company and his efforts to confront the challenges that face the American cigar industry in the form of prohibition and exorbitant taxes.

David Savona: So let's just talk about where you are and where you've come from. You're just coming off the success of the Decade. What's it like after more than 10 years in the business?
Rocky Patel: It's actually our 12th year now. It took us a while to find that perfect cigar to celebrate our 10-year anniversary, or decade, in the business. In order to commemorate our 10 years, we came up with the blend for the Decade. We probably went through about 120 different blends until I finally said we've got a cigar that's got a lot of flavor, it's got spice, richness, nuttiness, but balance. And we tried to do the same thing with more of a Nicaraguan puro in the ITC 10 Year.

Q: Wasn't the blend that became the ITC 10 originally going to be your Decade?
A: The original blend for the Decade was the ITC 10 Year. We liked that because it had a lot of character, it had a lot of body, it had a lot of spiciness. Then I came up with the blend we have now for the Decade, and decided that the Decade had that elegance and that balance, so we kind of flip-flopped. The original Decade was going to be the ITC, and the ITC was going to be the Decade.

Rest of the informative lengthy interview.

Angel Dust the inspiration for new Schizophrenia Drug

When scientists learned that PCP, also known as angel dust, can cause every single symptom of schizophrenia, they wondered if chemicals that have the opposite effect could fight mental disorders. That insight led to them to discover a new class of antipsychotic medications.

To understand how the recreational drug plays tricks on the mind, neuroscientists gave it to lab rats. Those researchers could counteract the strange behavior of their furry assistants by stimulating brain proteins called glutamate receptors. Big drug companies, including Eli Lilly, took note of that discovery and started searching for molecules that can push the same psychological buttons in humans.

In the Sep 15 issue of Chemical and Engineering News, Carmen Drahl told that story, along with the tales of three other experimental medications that could turn the tide against schizophrenia. Each compound operates in a completely different way, and all of them have been tested on human volunteers.

That is really big news because doctors have been stuck using the same class of pills -- dopamine blockers -- since the 1950's.

Drahl got the scoop on the new treatments during a special seminar about schizophrenia, which took place last month during the American Chemical Society meeting in Philadelphia.

LY404039 was discovered by Eli Lilly and works by activating glutamate receptors. It is furthest along in the approval process. Unlike other schizophrenia drugs, it does not cause excessive weight gain.
DCCCyB was developed by Merck, and it does the job by blocking glycine transporters
PF-2545920 was tested by Pfizer, and it gums up a phosphodiesterase enzyme.
TC-5619 was invented at Targacept and it excites nicotine receptors with far more precision than the finest cigarettes. Schizophrenics tend to medicate themselves by smoking, and new drug may offer them a similar kind of relief without the serious health risks that come from tobacco products.

If these drugs are approved by the FDA, the social implications could be profound: A great deal of homelessness is caused by psychological problems. Perhaps some of these new substances will allow people with serious mental illness to become functional and live somewhat normal lives.

Aluminum MacBooks possibly already shipping from manuf.

If we take the word of Citigroup analyst Richard Gardner, the much rumored new aluminum MacBooks are already winging their way from China to Apple's secret underground storage facility. This fits with speculation that we'll see a notebook refresh from Apple some time in October.

Gardner's "field checks" (read: crystal ball) have told him that the new MacBooks will have a “very thin aluminum casing, an LED-backlit display and an aggressive entry-level price point."

Aluminum makes sense. Everything else in the lineup is turning into aluminum (except the iPhone's rear case). LED backlighting also makes sense. And the "aggressive entry-level price point", combined with the iPod price drops, could be the mysterious "product transition" we keep hearing about.

Other parts of the internet will surely cry "fake", saying that new MacBooks would have been released for the back-to-school season. We say no. What better way to clear old inventory than to sell it off to the kids?

Shipments Have Begun On New MacBooks [Barrons via MacRumors]

See also:

Fake Mock-Ups of Aluminum-Clad MacBooks With Multitouch [Gadget Lab]

Spy-Shots Show Possible MacBook Pro Redesign [Gadget Lab]

WaMu lowered to junk by S&P

NEW YORK (CNNMoney.com) -- Washington Mutual's stock slumped as the market opened Tuesday, after Standard & Poor's lowered the savings-and-loan's credit rating lowered to junk amid continuing weakness in the housing market.

WaMu (WM, Fortune 500) shares plunged 15% after the opening bell, but the losses softened after a few minutes. About half an hour after the open, the stock was down 8%.

The Standard & Poor's action followed downgrades of the nation's largest S&L by Fitch Ratings and Moody's last week, as WaMu tries to reassure nervous investors that it has the ability to survive the credit crunch.

"Increasing market turmoil and the related impact from managing its concentrated mortgage franchise in this troubled housing and credit cycle led to the downgrade of WaMu," said Victoria Wagner, an S&P credit analyst, who lowered the bank's rating to BB- with a negative outlook.

Last week, Fitch Rating lowered WaMu to BBB- with a negative outlook, while Moody's took it down into junk territory with a Baa3 rating with a negative outlook.

S&P's announcement followed another brutal day for the bank on Wall Street. Shares plummeted nearly 27% to close at $2.

Investors are concerned that potential sources of capital have disappeared in the upheaval this weekend on Wall Street that saw Lehman Brothers (LEH, Fortune 500) file the nation's largest bankruptcy and Bank of America (BAC, Fortune 500) scoop up Merrill Lynch (MER, Fortune 500).

After this weekend's turmoil, however, WaMu has fewer places to turn if it needs another injection of capital beyond the $7 billion it raised in April. No one stepped in to save Lehman, and Bank of America will now be busy digesting Merrill. Meanwhile, JPMorgan Chase (JPM, Fortune 500) and Goldman Sachs (GS, Fortune 500) are reportedly trying to arrange $75 billion in loans for troubled insurer American International Group (AIG, Fortune 500).

WaMu is one of the largest players in the mortgage market, which brought it prosperity during the housing boom and may lead to its downfall during the bust.

Seeking to reassure investors, the bank said late Thursday that it had sufficient capital and liquidity to see it through these tough times. It reported that it plans to set aside $4.5 billion in the quarter for loan losses, down from $5.9 billion in the prior period but more than two times expected charge-offs, or uncollectable loan losses.

Reserves for loan losses should build to $10.3 billion, up from $8.5 billion.

The growth of net charge-offs is expected to slow to less than 20% in the quarter. In the prior period, charge-offs soared nearly 60%.

The bank said it expects its capital ratio, a measure of its ability to withstand loan losses, to remain "significantly above the levels for well-capitalized institutions." It has about $50 billion of liquidity from "reliable" funding sources.

Responding to S&P's downgrade, WaMu said: "S&P attributed its action to worsening market conditions, and not to any material change in the evaluation of Washington Mutual's financial condition. S&P's ratings for Washington Mutual Bank remain investment grade."

Analysts had mixed reaction to the report. Fitch Ratings and Moody's subsequently downgraded WaMu, concerned about its ability to raise capital, while other analysts voiced concerns about depositors' reactions.

"The biggest risk for WM is a run on deposits," said Chris Brendler, analyst with Stifel Nicolaus & Co. "With all the negative headlines and recent IndyMac failure, WM's retail deposit franchise is a huge concern to us, as a significant outflow of consumer deposits could lead to devastating liquidity problems since the company has apparently already lost access to the capital markets."

But some analysts said the report should restore some confidence in the company. They were heartened by the fact that the company feels it can put less aside for loan losses.

Even in downgrading the stock, S&P said it recognizes that the company has enough liquidity to meet all its fixed obligations through 2010 and is operating with enough capital from a regulatory perspective.

Other analysts agreed.

"Although not out of the woods yet, WM appears to be moving in the right direction on credit and 2008 is likely to be the peak year for provisioning," Fox-Pitt Kelton analysts wrote in a note to clients.

Goldman earnings sink 70%, stock down 10%

NEW YORK (CNNMoney.com) -- Goldman Sachs reported a sharp decline in profits Tuesday that beat Wall Street's forecasts. But revenues missed analysts' estimates and the stock plunged in early trading.

The New York City-based investment bank said its profits fell 70% to $845 million, or $1.81 a share, during the third quarter ending in August. Just a year ago, the company reported a profit of from $2.85 billion, or $6.13 a share.

Wall Street was expecting a profit of $1.71 a share.

Net revenue tumbled more than 50% to $6.04 billion from $12.3 billion during the same period last year, missing projections of $6.2 billion.

With investment banking activity at a virtual standstill and financial markets in disarray, few were expecting a banner quarter for Goldman.

After suffering through one of their worst drops of the year on Monday as the Dow fell more than 500 points, Goldman (GS, Fortune 500) shares continued to decline, falling more than 12% morning trading.

Investors were watching Goldman's results carefully in light of the rapidly changing financial landscape.

Fellow investment bank Lehman Brothers (LEH, Fortune 500) filed for bankruptcy Monday, marking the biggest ever in U.S. corporate history.

Merrill Lynch (MER, Fortune 500), a Wall Street icon known for its famous bull logo, also announced plans to be acquired for some $50 billion by Bank of America (BAC, Fortune 500), after enduring billions of dollars in losses as a result of ambitious bets on the U.S. mortgage market.

Goldman rival Morgan Stanley (MS, Fortune 500) is slated to report its quarterly results Wednesday.

Lloyd Blankfein, Goldman Sachs' chairman and CEO, described the quarter as challenging, blaming Tuesday's results on a decrease in client activity and declining asset valuations.

"Despite the deteriorating market conditions, the focus of our people and strength and breadth of our client franchise produced a solid performance in a tough environment," Blankfein said in a statement.

He added that the company remains "well-positioned to meet the needs of our clients and identify and act on the right market opportunities."

Investment banking, a cornerstone of the Goldman's business, was one of the hardest hit divisions of the company. Revenues in the division plunged 40% as advisory and underwriting activity stalled during the quarter.

But it was Goldman's trading and principal investment division, which includes the company's equity, fixed income, currency and commodities businesses, that suffered the most. Revenues fell by two thirds during the quarter to $2.7 billion.

Analysts warned ahead of Tuesday's earnings announcement that the division could see signs of strain since Goldman Sachs ties more of its business to the stock market than any of its peers.

Bucking the trend was the company's asset management and securities business, which reported a 4% increase in revenue during the quarter.

Despite this quarter's woes, Goldman continues to remain relatively well capitalized. The company said its Tier 1 capital ratio - a widely used measure of a bank's ability to absorb losses - stood at 11.6%, up from 10.8% in the previous quarter.

A Tier 1 capital ratio of above 8% is generally considered a good sign for financial institutions.

Pentagon researcher illustrates possiblity of World of Warcraft based Terror Plot

The American military and intelligence communities are increasingly worried that would-be bin Ladens might gather in a virtual world, to plan a real-life attack. But the spies haven't given many details, about how it might be done. Now, a Pentagon researcher has laid out how such a terror plot might unfold. The planning ground is World of Warcraft. The main target of this possibly nuclear strike: the White House.

There's been no public proof to date of terrorists hatching plots in virtual worlds. But online spaces like World of Warcraft are making some spooks, generals and Congressmen extremely nervous. They imagine terrorists rehearsing attacks in these worlds, just like the U.S. military trains with commercial shoot-em-up games. They worry that the massively multiplayer games make it incredibly easy to gather plotters from around the world. But, mostly, virtual worlds are nerve-wracking to spies because they're so hard to monitor. The accounts are pseudonymous. The access is global. The jargon is thick. And most of the spy agencies' employees aren't exactly level-70 shamans.

In a presentation late last week at the Director of National Intelligence Open Source Conference in Washington, Dr. Dwight Toavs, a professor at the Pentagon-funded National Defense University, gave a bit of a primer on virtual worlds to an audience largely ignorant about what happens in these online spaces. Then he launched into a scenario, to demonstrate how a meatspace plot might be hidden by in-game chatter.

In it, two World of Warcraft players discuss a raid on the "White Keep" inside the "Stonetalon Mountains." The major objective is to set off a "Dragon Fire spell" inside, and make off with "110 Gold and 234 Silver" in treasure. "No one will dance there for a hundred years after this spell is cast," one player, "war_monger," crows.

Except, in this case, the White Keep is at 1600 Pennsylvania Avenue. "Dragon Fire" is an unconventional weapon. And "110 Gold and 234 Silver" tells the plotters how to align the game's map with one of Washington, D.C.

The fictional plot was originally developed by Dan Arey, for the Director of National Intelligence's Summer Hard Problems workshop, or SHARP. And its details are a little fuzzy. The terminology doesn't match World of Warcraft lingo, all that precisely. There is no "White Keep" in World of Warcraft; "Dragon Fire" is a spell in EverQuest, the old-school role-playing game, not WoW. But the banter is reminiscent enough of World of Warcraft talk, to give outsiders an idea of how such a conversation might go down -- and how hard it would be to identify.

Steven Aftergood, the Federation of the American Scientists analyst who's been following the intelligence community for years, wonders how realistic these sorts of scenarios are, really. "This concern is out there. But it has to be viewed in context. It's the job of intelligence agencies to anticipate threats and counter them. With that orientation, they're always going to give more weight to a particular scenario than an objective analysis would allow," he tells Danger Room. "Could terrorists use Second Life? Sure, they can use anything. But is it a significant augmentation? That's not obvious. It's a scenario that an intelligence officer is duty-bound to consider. That's all."

Toavs, for one, believes that spies will have to spend more time in virtual worlds like WoW, if they want to have a hope of keeping tabs on what goes on inside 'em. Which means, some day soon, we might find secret agents in World of Warcraft, along with the druids and orcs and night elves.

HP cuts 25,000 Jobs

SAN FRANCISCO (AP) -- When Hewlett-Packard Co. announced five months ago it was acquiring technology-services firm Electronic Data Systems Corp., Wall Street expected big layoffs from the combined company.

But the size of the job cuts - 24,600 jobs over the next three years, nearly 8 percent of HP's 320,000-employee work force - came as a shock when HP laid out its plans Monday for integrating EDS.

The surprise could provide a lift for Palo Alto-based HP's stock price Tuesday because of the potential cost savings from the dramatic reduction in staff and HP Chief Executive Mark Hurd's track record for wringing more profits out of lean operations.

"Today's story is kind of an eyebrow-raiser - I was surprised at the magnitude of the cuts," said analyst Bob Djurdjevic with Annex Research.

Djurdjevic added that EDS had been cutting jobs before HP bought it, and some investors were concerned those cutbacks weren't addressing a key problem for EDS in the need to ink more profitable deals. That challenge now falls to HP.

The cuts represent HP's most aggressive cost-cutting move yet under Hurd, who engineered the $13.9 billion acquisition to challenge IBM Corp. for more of the lucrative, long-term business of helping companies manage their computing infrastructure.

Most of the cuts will come from within EDS's ranks, and nearly half will be jobs in the U.S., HP announced Monday after the stock market closed. HP said it plans to eventually add about half the positions back as different jobs in different departments within the company.

Some of the areas expected to get hit include the finance, human resources and legal departments, areas where there are traditionally overlapping duties within combined companies.

HP had not previously detailed how many employees of the combined company would lose their jobs. Before the acquisition, HP had 178,000 people and EDS had 142,000.

HP expects to save $1.8 billion per year from the cuts once the restructuring is complete. The company will incur a $1.7 billion charge in the current three-month period, its fiscal fourth quarter, for a goodwill adjustment and other costs connected to the restructuring.

At a conference with financial analysts Monday, HP Chief Financial Officer Cathie Lesjak said the EDS deal is expected to add to HP's net profit in the 2010 fiscal year.

Until then, HP is planning for the acquisition to reduce net income by 17 cents to 19 cents a share in the current quarter, which ends Oct. 31, and 6 cents to 11 cents per share in the 2009 fiscal year, Lesjak said at the conference in San Francisco.

As huge as the reductions are, they're not the biggest in tech history.

In the early 1990s, Armonk, N.Y.-based IBM shed more than 150,000 workers over a five-year stretch as it racked up nearly $16 billion in losses and faced questions about its survival.

With the addition of EDS, HP hopes to challenge IBM's core services business in a bigger way.

HP and EDS had a combined $38.8 billion in services revenue last year. The combined sales eclipsed HP's revenues from its personal-computer division, HP's biggest business unit for that period. HP is the world's No. 1 seller of PCs worldwide.

IBM had $51.4 billion in total technology and business-services revenue in 2007.

Competition for services contracts is intensifying as businesses look for ways to offload some of their information-technology chores. Rising energy prices and demand for more computing power has made deploying new technology more costly and complicated, a combination that makes outsourcing those duties increasingly attractive for companies looking to cut costs.

The turmoil on Wall Street has actually increased demand for those services in some sectors because it's often viewed as an investment that can help companies save money over the long term.

One of the biggest challenges facing Hurd has been finding new ways to improve sales at a company that last year cracked $100 billion in revenue for the first time while keeping Wall Street happy with improving profit margins.

Hurd has been aggressive about cutting costs since he was hired in 2005. His first big act was a major restructuring that eliminated nearly 15,000 jobs.

Hurd's changes have helped HP wring more profits from its businesses even as the personal-computer industry as a whole grapples with shrinking profit margins, and HP's crown-jewel business - printer ink - faces intensifying competition from lower-cost competitors.

HP shares fell $1.64, or 3.5 percent, to $45.33 in regular-session trading. In after-hours trading, the stock gained 37 cents to $45.70.

Algal Jet Fuel Closer to Reality

Commercial airlines won't stop using petroleum anytime soon, but a California startup says it has produced the world's first microbial-derived jet fuel, and independent tests show it behaves just like the stuff refined from oil.

Solazyme says analysis of its algal jet fuel by the Southwest Testing Institute showed it didn't freeze at high altitude -- a common problem with biofuels -- and it had the same density, stability and flashpoint of conventional jet fuel. In all, the algal fuel met 11 of the most challenging standards, known as D1655, for aviation fuels set by the ASTM. That's a significant step toward commercial viability of an alternative fuel that can meet the rigorous demands of the aviation industry.

"The Solazyme algae-based aviation kerosene has passed the biggest hurdles needed to successfully develop a commercial and military jet fuel fully consistent with existing engines and infrastructure," the company says.

That doesn't mean your next flight will be aboard a plane fueled by pond scum.

Several companies are experimenting with bio-jet fuels derived from soybeans and other feed stocks, but Solazyme makes fuel by growing algae in fermentation tanks without sunlight, satisfying the eukaryotic organism's sweet tooth by feeding it a steady diet of sugar. The process has already led to algal fuel for cars, called Soladiesel, that works like conventional diesel fuel. Solazyme hopes to begin mass-producing it at a competitive price within three years. That could be optimistic, but Chevron is sufficiently impressed to join Solazyme in the endeavor.

Solazyme isn't alone in pursuing algal jet fuel. Seattle-based Inventure Chemical is building a test plant and Texas-based PetroSun has dedicated part of its 1,100-saltwater-pond network to developing an algae-derived aviation fuel. Airlines and aircraft manufacturers, anxiously watching petroleum prices wreak havoc on their finances, are eager to give these new alternatives a try. Virgin Atlantic ran a biofuel test flight in February, while KLM, Continental, JetBlue, and Air New Zealand have announced plans to work with Boeing or Airbus on trials of their own. Darpa and the Air Force also are keenly interested in finding alternatives to kerosene.

The news from Solazyme is good, but don't plan to buckle yourself into an algae-powered jet anytime soon. While the innovation is there, the ability to scale up isn't. Company CEO Jonathan Wolfson says the company could produce millions of gallons of algal kerosene if it had the equipment, but the "capital involved in owning that equipment is massive." And then there's the fact algal kerosene still costs more than the stuff refined from petroleum.

Photo by Flickr user Micah A. Ponce.

Pressure mounts on AIG with Downgrades- Fed asks Goldman JP Morgan for help

NEW YORK (CNNMoney.com) -- The pressure on American International Group reached fevered pitch on Monday night as the troubled insurer was hit by a series of credit rating downgrades.

The cuts could prove deadly to AIG, the nation's largest insurance company, which is scrambling to raise much-needed capital.

Late Monday night, Moody's Investors Service and Standard & Poor's Ratings Services each said they had lowered their ratings.

A few hours earlier, Fitch Rating had also downgraded AIG, saying the company's ability to raise cash is "extremely limited" because of its plummeting stock price, widening yields on its debt, and difficult capital market conditions.

The downgrades will make it more expensive for AIG to issue debt and harder for it to regain the confidence of investors.

Fitch said AIG could be required to post $10.5 billion of additional collateral if it was downgraded one notch by one of the other major rating agencies and $13.3 billion of collateral if downgraded by both, Fitch said in a statement, citing AIG's July 31 estimates.

The grim assessments came after a day in which state and federal officials raced to help the insurer gain access to much needed cash.

The company has lost more than $18 billion in the past nine months.

The credit downgrades could doom its business.

AIG did not immediately reply to a request for comment on the late-night downgrades.

New York State gave AIG, the nation's largest insurer, the power to transfer $20 billion in assets from its subsidiaries to use as collateral for daily operations, said Gov. David Paterson. In exchange, the parent company will give the subsidiaries less-liquid assets.

"It is simply giving AIG (AIG, Fortune 500) in effect the ability to provide a bridge loan to itself," said Paterson, stressing the company is financially sound and that no taxpayer dollars are involved.

Meanwhile, the Federal Reserve asked Goldman Sachs (GS, Fortune 500) and JPMorgan Chase (JPM, Fortune 500) to make $70 billion to $75 billion in loans available to AIG, the Wall Street Journal reported.

However, any discussions are very preliminary, a source close to the matter told CNNMoney.com.

Also, the Fed has hired Morgan Stanley (MS, Fortune 500) to examine alternatives for AIG and determine whether the government should help the insurer, a source said.

JPMorgan and the Fed declined to comment, while Goldman and Morgan Stanley did not immediately return requests for comment.

Shares plummet 61%

Wall Street had expected AIG to issue a restructuring plan that would address its capital crunch and boost investor confidence. But the company, a component of the benchmark Dow Jones industrial average, remained silent.

Investors punished the stock, sending it down 61% to close at $4.76 Monday. The company, which has been rocked by the subprime crisis, has seen its stock price fall more than 91% so far this year.

The New York Times reported late Sunday night that the company is seeking a $40 billion bridge loan from the Federal Reserve. A source close to the firm said that if AIG does not raise cash and is downgraded by ratings agencies, it may have only 48 to 72 hours to survive.

The restructuring plan was expected to include the sale of assets, including its annuities unit and its domestic auto insurance business, the Journal reported Sunday. It may also look to dispose of its aircraft-leasing arm, International Lease Finance Corp., which has a fleet of more than 900 airplanes valued at more than $50 billion.

AIG spokesman Nicholas Ashooh told CNNMoney.com on Monday that the company is "still evaluating alternatives."

The ailing company, which had planned to announce a turnaround strategy on Sept. 25, is being forced to accelerate the announcement after investors fled the stock last week.

The company is likely to sell its personal insurance and annuities businesses and the aircraft leasing unit, wrote Joshua Shanker, a Citigroup analyst, who believes the company might have to mark down another $30 billion in assets.

"We believe AIG will survive, but we have little indication of how many business lines will ultimately need to be sold and how dilutive to shareholders future capital raising efforts will be," Shanker wrote.

AIG, which already raised $20 billion in fresh capital earlier this year, has been pummeled by three quarters of huge losses and writedowns.

Its troubles stem from its sales of credit default swaps - insurance-like contracts that guarantee against a company defaulting on its debt - and from its subprime mortgage-backed securities holdings.

AIG has written down the value of the credit default swaps by $14.7 billion, pretax, in the first two quarters of this year, and has had to write down the value of its mortgage-backed securities as the housing market soured.

The insurer could be forced to immediately come up with $18 billion to support its credit swap business if its ratings fall by as little as one notch, wrote John Hall, an analyst at Wachovia.

But the company has many attractive businesses it could sell to raise capital, he said.

"We think investors need to divorce themselves of the notion that the AIG which emerges from these problems will resemble the insurance titan of the past," Hall wrote.

This year's results have also included $12.2 billion in pretax writedowns, primarily because of "severe, rapid declines" in certain mortgage-backed securities and other investments.

What happens to AIG now depends on its ability to sell assets and to unleash the assets in its subsidiaries, Fitch said.

AIG has struggled all year as the Wall Street credit crunch took its toll.

In June, the company tossed out its chief executive, Martin Sullivan, who had been charged with turning the company around after directors removed longtime CEO Hank Greenberg in 2005. Greenberg was the target of one of then-Attorney General Eliot Spitzer's investigations.

The board named AIG chairman Robert Willumstad, who joined AIG in 2006 after serving as president and chief operating officer of Citigroup (C, Fortune 500), to replace Sullivan as chief executive officer.

Though AIG's problems have been apparent for months, it is coming under fire now because of Wall Street's increasing skittishness over Lehman Brothers, also a big player in credit default swaps, said Chip MacDonald, partner in the capital markets group at Jones Day, a law firm.

"It's the lack of transparency and clarity about their business," MacDonald said. "In today's environment, everyone is assuming the worst so they are forcing AIG to come out with a plan sooner rather than later."

However, MacDonald noted, AIG is not in as vulnerable a position as other financial institutions because of its core insurance business. Customers cannot simply withdraw their deposits, as they can at a bank.

"It's a little harder to make a run on an insurance company," MacDonald said.

DNA in Real Time

Super sequencing: The small rectangle sitting on the center of the glass slide is Pacific Biosciences’ sequencing chip. It contains thousands of tiny wells, each 10 nanometers in diameter, which house individual sequencing reactions. Laser light shined from below can penetrate only the bottom 20 to 30 nanometers of each well, illuminating a tiny window in which to observe a single base being added to a strand of DNA. Credit: Pacific Biosciences

In a nondescript office park in the northeast side of Menlo Park, CA, the next genomics revolution may be taking place. There, 12 prototypes of a new sequencing machine developed by startup Pacific Biosciences are churning out reams of DNA sequence as fast as built-in cameras can record it. The deep freezer-size boxes, covered for the time being in red plastic sheeting, are performing a novel feat: reading single strands of DNA in real time. The machine's creators hope that innovation will result in a process that operates fast and cheaply enough to make sequencing a routine component of medical care.

The company, founded in 2004, made a splashy debut almost a year ago, showcasing its technology to the scientific community for the first time at a sequencing conference in Florida. Steve Turner, the company's founder and chief technology officer, wowed the audience with a video of single molecule sequencing in progress, the product of a proof-of-principle experiment reading a 150-base-pair length of DNA. Since then, the startup has garnered $100 million more in funding--for a total of $178 million to date.

Pacific Biosciences' central innovation is a small chip composed of a 100-nanometer-thick metal film deposited on a silicon-dioxide substrate and dotted with thousands of tiny wells, each only tens of nanometers in diameter. Before sequencing begins, an enzyme called DNA polymerase is immobilized at the bottom of the well, along with the strand of DNA to be read. Fluorescently labeled bases--each of the four DNA letters labeled with a different marker--are then flooded onto the plate, randomly diffusing into each well. When the correct base diffuses into the bottom of a well, the enzyme attaches it to the growing strand of DNA.

The wells are so small that fluorescent light shined through the bottom of the plate penetrates only the lower 20 to 30 nanometers of each well, meaning that only the bases being actively attached to the DNA molecule light up. That allows a camera to capture the sequencing reaction as it happens, leaving any irrelevant chemical activity in the dark. "The waveguide is the first technology to allow observation of the polymerase in action at physiologically relevant concentrations," says Turner.

In a video showing the sequencing reactions in action, a series of lights scattered across the screen burst and fade in quick succession. (A computer detects which base is added with each burst by its position within a well.) The machines can currently sequence 12 million bases of DNA per hour, about one-third of a percent of a human genome. The video must actually be slowed to be viewed: the reactions occur too fast to be visible to the human eye.

Despite its early success, it's not yet clear whether the company's innovative approach will surpass "next generation" sequencing technologies already in use. Pacific Biosciences plans to release a commercial product in 2010 and will announce the target sequencing capacity for that machine early next year. New types of sequencing machines, such as those developed by Roche Applied Sciences and Illumina, have already revolutionized genomics, allowing scientists to sequence huge volumes of DNA and reportedly dropping the cost of a human genome to less than $100,000.

But Turner is confident that his method has advantages, especially in the clinical diagnostics market. The most advanced sequencing approaches currently on the market stop the sequencing reaction after the addition of each base, wash away extra bases, snap a picture, and then repeat. Real-time sequencing is faster and uses fewer chemicals, making it much cheaper. "In the long run, the reagent cost dominates in sequencing," says Chad Nusbaum, codirector of the Genome Sequencing and Analysis program at the Broad Institute, in Cambridge, MA.

DNA detection: This illustration shows a single 10-nanometer well, one of thousands on Pacific Biosciences’ chip. A DNA polymerase enzyme (shown in white) is immobilized at the bottom, with a piece of single-stranded DNA (shown in purple). Fluorescently labeled bases, each marked with a different color (shown here as gray shapes with red, orange, blue, or green circles), randomly diffuse into the well. When the polymerase enzyme detects that the correct base is present, it attaches the fluorescent molecule to the growing strand of DNA. Fluorescent light shines from below, illuminating that reaction, which is captured by a camera. The polymerase then moves to the next position on the strand. Credit: Pacific Biosciences

Both Roche and Illumina have ramped up speed by running a massive number of sequencing reactions in parallel. However, these methods generate relatively short lengths of sequence, about 50 to 200 bases pairs, which must then be computationally assembled into a complete sequence. The shorter the piece, the more computationally difficult it is to sew them together. "With a 35 base read, you can't assemble 25 percent of the genome," says Turner.

Pacific Biosciences has already generated what Turner believes to be "the longest sequencing trace ever made." In a proof-of-principle experiment, scientists continuously sequenced the same 135 base circle of DNA 12 times--it was like repeatedly driving around a rotary. While the company hasn't yet repeated the feat with natural DNA, the ability to generate long reads could be especially important when sequencing unknown DNA or stretches with a highly repetitive series of bases. "Many of the dynamic regions of the genome that are associated with disease consist of duplicated and complex repetitive sequences that cannot be accurately assessed at present," says Evan Eichler, a geneticist at the University of Washington, in Seattle. "Long-sequence reads are necessary to comprehensively understand human genetic variation."

Pacific Biosciences' machine may also enable scientists to generate more accurate sequences. Existing methods generate a consensus sequence by reading the same section of multiple copies of DNA, which may have some copying errors, and pooling the results. "All short-read technologies are less accurate than traditional methods," says Nusbaum. With Pacific Biosciences technology, scientists would theoretically be able to sequence the same piece of DNA multiple times. "That means we'll be able to detect rare mutations with unprecedented accuracy, orders of magnitude better than others," says Turner.

He adds that the long reads, high accuracy, and quick turnaround time make the technology ideal for diagnostics, such as those for cancer, which involves long stretches of repetitive sequences, and infectious disease, in which small sequence changes may drastically change the infectiousness and virulence of a pathogen.

Perhaps the biggest excitement comes from Turner's predictions for the future. He says that it will be easy to further improve the company's technology with higher-resolution cameras, faster DNA polymerases, and more densely packed chips. Currently, each chip has thousands of wells, only about one-third of which are used. (The remaining two-thirds house either no enzyme molecules or more than one, and thus fail to generate useful information.) But the chips, which are created using semiconductor fabrication methods, have the capacity to hold 10 million wells.

Turner calculates that with a camera that can track one million wells, a polymerase that operates at about 50 bases per hour (the current rate is 10), and full use of all the wells on the plate, Pacific Biosciences technology could read 100 gigabases an hour. That translates to full coverage of a human genome--the same genome sequenced 15 times--in just 15 minutes.

"I'm pretty excited about the possibilities of this technology, but I remain to be convinced," says Nusbaum. "They still have some significant technical hurdles ahead of them."

Nanoflowers Improve Ultracapcitors

Nanoflower power: A transmission electron microscope image shows a flowerlike manganese oxide nanoparticle deposited at the junction of crossed carbon nanotubes. Used as an electrode material, this nanotube-manganese-oxide composite could improve the energy-storage ability of ultracapacitors, which show promise as powerful, long-lasting replacements for batteries. Credit: American Chemical Society

Imagine a cell-phone battery that recharges in a few seconds and that you would never have to replace. That's the promise of energy-storage devices known as ultracapacitors, but at present, they can store only about 5 percent as much energy as lithium-ion batteries. An advance by researchers at the Research Institute of Chemical Defense, in China, could boost ultracapacitors' ability to store energy.

A capacitor consists of two electrodes with opposite charges, often separated by an insulator that keeps electrons from jumping directly between them. The researchers have developed an electrode that can store twice as much charge as the activated-carbon electrodes used in current ultracapacitors. The new electrode contains flower-shaped manganese oxide nanoparticles deposited on vertically grown carbon nanotubes.

The electrode design promises to deliver more power, says Hao Zhang, lead author of the Nano Letters paper describing the new work. The electrode's longevity also compares with that of activated-carbon electrodes, Zhang says: discharging and recharging the electrodes 20,000 times reduced the capacitor's energy-storage capacity by only 3 percent.

In a typical ultracapacitor, two aluminum electrodes are suspended in an electrolyte. A voltage applied to the electrodes separates the positive and negative ions in the electrolyte, which get attracted to the oppositely charged electrodes. How much energy the ultracapacitor can store largely depends on the electrodes' surface area: the more area, the more space to store charge. Coating the electrodes with activated carbon increases their surface area, since a teaspoonful of the porous, spongelike material has about the surface area of a football field. Ultracapacitors can store millions of times more energy than the tiny capacitors used in electronic circuits.

But their performance still pales beside that of batteries, which store energy using chemical reactions. "If I gave you a cell phone with an ultracapacitor battery, you'd never replace the battery, and you could recharge it in a few seconds, but it would only last half an hour," says Joel Schindall, an electrical-engineering professor at MIT.

So far, ultracapacitors have been limited to niche applications that require high power and quick, repetitive recharging. For example, the devices provide quick bursts of power to buses, trucks, and light-rail trains over short stretches, and braking replenishes them. If they could store more energy, however, they could be a powerful, long-lasting replacement for batteries in hybrid-electric vehicles and portable electronics.

Researchers have long sought to boost energy storage in ultracapacitors by improving electrode design. Schindall and his colleagues are trying to make electrodes coated with carbon nanotubes, which have a greater surface area than activated carbon and are excellent conductors. Other research groups are using better charge-storing materials, such as manganese oxide and conducting polymers.

The new electrode combines the advantages of these two methods. First, the researchers grow an array of carbon nanotubes on a foil made from the metal tantalum, which is commonly used in capacitors. Then they grow 100-nanometer-wide flower-shaped nanoparticles directly on the array. The nanotubes grow more or less vertically, but they're not very stiff and tend to fall across each other. The nanoflowers grow mostly at the junctions of multiple nanotubes and have a large surface area (236 square meters per gram) compared with typical particles of manganese oxide.

"Each manganese oxide nanoflower is connected directly with the tantalum foil by two or more electron superhighways, the carbon nanotubes," says Gaoping Cao, Zhang's coleader on the project. "This superior conducting network allows for efficient charge transport." When current flows through the tantalum foil, charges quickly get transferred to and stored in the manganese oxide: the electrode stores twice as much charge as the same volume of activated carbon. The nanotubes' high conductivity could also give them a greater power output than current ultracapacitors have, the researchers say.

"The way of growing manganese oxide on carbon nanotube arrays is new and has produced beautiful structures," says Yury Gogotsi, a materials-science and engineering professor at Drexel University. Gogotsi says that combining the high conductivity of the carbon nanotubes with the charge-storage capacity of manganese oxide is an attractive approach. But, he adds, "it is not practical for large volume, such as automotive applications, because the use of carbon nanotube arrays and tantalum foil makes them expensive."

Indeed, says Schindall, cost could be the main barrier to ultracapacitors with nanostructured electrodes. "They've found a way to grow these structures," he says, "but now they've got to be able to grow them densely enough and economically enough to be practical."

Judge says Feds violated 10th Amendment by subverting state marijuana laws

As It Stands by Dave Stancliff/For the Times-Standard

A landmark decision for all Californian's quietly made history on August 20th in a Santa Cruz courtroom.

For the first time since 1996, when the Compassionate Use Act was passed, the federal authorities have been charged with violating the 10th Amendment for harassing medical marijuana patients and state authorities.

The case of Santa Cruz vs. Mukasey, was heard by U.S. District Court Judge Jeremy Fogel, who said the Bush Administration's request to dismiss a lawsuit by Santa Cruz city and county officials, and the Wo/Men's Alliance for Medical Marijuana (WAMM), wasn't going to happen.

In a recent telephone interview with Alan Hopper, an ACLU counsel familiar with the case, I asked him what came next?

”The plaintiff will get a get a court-ordered discovery document that will allow them to get documents, and even depositions, from the federal authorities to support their claims,” he explained.

So now it's the city, county, and WAMM's turn to prove their case against the federal government. The court has recognized a concerted effort by the federal government to sabotage state medical marijuana laws, which violates the U.S. Constitution. The significance of this ruling, the first of its kind, cannot be overstated.

California voters may finally get what they asked for a dozen years ago. When the court said that the federal government had gone out of its way to arrest and prosecute some of the most legitimate doctors, patients, caregivers, and dispensary owners that had been working with state and local officials, it finally drew a line-in-the sand.

An example of the federal authorities violations was their pursuit of WAMM. This non-profit group has been around for many years, and has been fully supported by the city and county of Santa Cruz. They have been referred to, by officials, as the model medical marijuana patient's collective.

The group was functioning so smoothly that the city even allowed them to hold regular meetings to distribute marijuana to its patients on the steps of city hall! The federal agents still went after them, which brought about this court decision.

When the ACLU filed this lawsuit to stop them from targeting medical marijuana providers and patients, they opened a door that may finally lead to no federal interference in California's medical marijuana law.

We must not forget that medical marijuana brings in about $100 million each year in tax revenue. Conferring total legitimacy to the law will allow this cash flow to continue, and hopefully, increase over time.

When the judge ruled the feds were threatening physicians who recommended marijuana, he set the stage for regaining patient's rights. The ruling clearly pointed out that the feds were also threatening government officials who issue medical marijuana cards, and interfered with municipal zoning plans.

In the summation, the court found that, “There was a calculated pattern of selective arrests and prosecutions by the federal government with the intent to render California's medical marijuana laws impossible to implement and therefore forced Californian's and their political subdivisions to re-criminalize medical marijuana.”

In a recent column, I mentioned California's Attorney General Jerry Brown had passed out an 11-page directive that all law agencies were to go by. I expressed concern that the federal authorities would ignore those guidelines, but upon finding out about this recent ruling I now have some cause for hope.

It sure sounded like Hopper was looking forward to the next phase, and he seemed confident that positive change lay ahead. Asked which presidential candidate would be more amenable to upholding medical marijuana laws, he cleverly replied that he thought they both would be willing to work for change. He could be right too. This is a year of change.

This on-going battle with the federal authorities ignoring California's laws has been well-documented in the past. Why hasn't there been more coverage for such an epic ruling? Its potential as breakthrough legislation is something all Californian's should know about in my opinion.

The war against medical marijuana hasn't been won yet, but this could be the breakthrough everybody's waited for. At the core of the war waged by the federal government against the voter's will, is the failed War on Drugs by the Bush Administration. It's about time someone told them to back off.

As It Stands, we can score this as a successful round for state's rights.

872,721 marijuana arrests in 2007, up 5.2% from 2006

Record number of Americans arrested for marijuana

The FBI has released its annual report on Crime in the United States 2007. Once again, the number of people in the United States arrested for marijuana has gone up. 872,721 Americans were arrested for marijuana in 2007, and of those arrests, 89% or 775,138 were arrests for simple possession - not buying, selling, trafficking, or manufacture (growing).

This represents an increase in marijuana arrests of 5.2% from the previous year and the fifth straight year marijuana arrests have increased from the previous year. Now a marijuana smoker is arrested at the rate of 1 every 37 seconds and almost 100 marijuana arrests per hour.

Marijuana possession is increasingly the bulk of the “War on Drugs”

More arrests for marijuana are for simple possession than for any other drug. While only 11% of marijuana arrests involve buying, selling, trafficking, or manufacture, that rate for heroin and cocaine is 27% and that rate for synthetic drugs is 31%.

While arrests for marijuana sales/manufacturing increased by 7.6% over 2006, heroin and cocaine sales/manufacturing arrests dropped by 3.8% and synthetic drugs sales/manufacturing arrests dropped 2.6%.

While arrests for marijuana possession rose by 4.9%, heroin and cocaine possession arrests fell by 8.1% and synthetic drugs possession arrests fell by 5.4%.

Overall, while arrests for marijuana increased by 5.2%, arrests for all other drugs combined dropped from 1,060,183 to 968,461, a decline of 8.7%. Last year, marijuana arrests made up 43.9% of all drug arrests. This year, marijuana accounts for 47.4% of all drug arrests. Almost half of the war on drugs is waged on marijuana.

The West is the Best

The FBI breaks their data down into four regions: Northeast, Midwest, South, And West. Arrests for marijuana make up more than half of all drug arrests in two out of four regions and almost half in a third. The Midwest leads the charge with 60.8% of its drug arrests for marijuana, followed by the South with 52.5% of its arrests and the Northeast with 49.9% of its arrests. In the West, marijuana arrests only make up a little more than one-third of the drug arrest total at 34.3%.

This is the first time most of the country is dedicating most of its drug arrests toward marijuana. In the previous year, only the Midwest, at 57%, surpassed 50%, with the South coming in at 49.8%, the Northeast at 47.9%, and the West at 30%.

Accounting for population of these regions, marijuana users in the South are most at risk, where there are 318 marijuana possession arrests for every 100,000 Southerners. Midwesterners face a 292-to-100,000 ratio, in the Northeast it is 225-to-100,000, and only 201 per 100,000 Westerners are arrested for marijuana possession.

Over past five years, more arrests for marijuana than all violent crime combined

Perhaps most disturbing is comparing marijuana arrests to violent crime. This year, while 775,138 Americans were arrested for mere marijuana possession, only 597,447 people were arrested for all violent crimes combined, which includes murder, non-negligent manslaughter, forcible rape, robbery, and aggravated assault.

While the percentage of marijuana possession arrests rose by 5.2%, arrests for violent crime dropped by 2.3% from the previous year. Now, to be fair, the reported incidents of violent crime did show a slight decrease of 0.7%, from 1,417,745 in 2006 to 1,408,337 in 2007, but that’s only a decrease of 9,408 offenses, compared to a decrease of 14,076 arrests for those offenses.

Over the past five years, there have been more arrests every year for marijuana possession than for all violent crime combined. Over those five years, murders have increased 2.3% and robberies have increased 7.5%. Overall, there were 24,661 more violent crimes in 2007 than in 2003, yet there were only 421 more arrests for violent crime in 2007 compared to 2003. This year there were only 424 arrests for every 1000 violent crimes, which is 7-to-10 fewer arrests per 1000 than each of the previous four years.

Ten Year Trend

Over the past ten years, arrests for just about every crime have declined. Arrests for all violent crimes have dropped by 8.9% and property crime arrests declined 12.5%. Many other miscellaneous crime arrests have seen double-digit percentage declines, like fraud (-30.8%), prostitution (-22%), and offenses against family and children (-16.9%). Meanwhile, in that ten years, the only crimes for which arrests have gone up are robbery (+5.9%), drug law violations (+17.6%), and embezzlement (+26.5%).