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Evolving Concepts in G Protein-Coupled Receptor Endocytosis: The Role in Receptor Desensitization and Signaling

CiteULike: Borelli's watchlist

- 21 hours and 1 minutes ago

Pharmacological Reviews, Vol. 53, No. 1. (1 March 2001), pp. 1-24.

G protein-coupled receptors (GPCRs) are seven transmembrane proteins that form the largest single family of integral membrane receptors. GPCRs transduce information provided by extracellular stimuli into intracellular second messengers via their coupling to heterotrimeric G proteins and the subsequent regulation of a diverse variety of effector systems. Agonist activation of GPCRs also initiates processes that are involved in the feedback desensitization of GPCR responsiveness, the internalization of GPCRs, and the coupling of GPCRs to heterotrimeric G protein-independent signal transduction pathways. GPCR desensitization occurs as a consequence of G protein uncoupling in response to phosphorylation by both second messenger-dependent protein kinases and G protein-coupled receptor kinases (GRKs). GRK-mediated receptor phosphorylation promotes the binding of Î²-arrestins, which not only uncouple receptors from heterotrimeric G proteins but also target many GPCRs for internalization in clathrin-coated vesicles. Î²-Arrestin-dependent endocytosis of GPCRs involves the direct interaction of the carboxyl-terminal tail domain of Î²-arrestins with both Î²-adaptin and clathrin. The focus of this review is the current and evolving understanding of the contribution of GRKs, Î²-arrestins, and endocytosis to GPCR-specific patterns of desensitization and resensitization. In addition to their role as GPCR-specific endocytic adaptor proteins, Î²-arrestins also serve as molecular scaffolds that foster the formation of alternative, heterotrimeric G protein-independent signal transduction complexes. Similar to what is observed for GPCR desensitization and resensitization, Î²-arrestin-dependent GPCR internalization is involved in the intracellular compartmentalization of these protein complexes.
Stephen Ferguson

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Last Weekend at Emerald City 2010 (or, the Cartooning Class Reunion)

Eco-luxury hotel in the Maldives

Guardian Unlimited

- 23 hours and 52 minutes ago

Can a luxury resort ever be green? A new hotel on the Maldivian island of Hadahaa is a true eco-paradise

With great pride, our "butler" Atheef is describing the utter deliciousness, the supreme sweetness, the irresistible flavour and vast superiority of the Maldivian mango. When I offer the Indian mango in comparison, he snorts with derision: the Maldivian variety is clearly in a much higher league. It's also only available in this island paradise for two months of the year, and as Atheef speaks I have a flashback to childhood and the giddy excitement of strawberries coming into season â€“ a delight wholly unknown to my own children, for whom such exotic delicacies are these days pedestrian staples thanks to the global food market.

The Maldives, however, is not the place to get radical about eating only local, or indeed seasonal, foodstuffs: these idyllic islands rely on imported produce, and working out how to feed themselves while striving to become the first carbon-neutral nation on earth is one of the many conundrums facing the inhabitants of this breathtaking collection of islands. There are 1,190 of them in all, scattered among some of the most pristine coral reefs in the Indian Ocean, and at two metres above sea level this vacation paradise is one of the most threatened nations on earth. The most pessimistic estimates suggest that they will be underwater by the beginning of the next century, a danger their energetic new president, Mohamed Nasheed, is striving to publicise to the international community â€“ last October the entire cabinet donned scuba gear and met underwater.

As a result of the very real threat on their doorstep, words like "sustainability", whispered among a very few of the forward-thinking hotels a decade ago, are now littered generously throughout their brochures. The bonanza that took place in the 1980s and 90s, turning the area around the capital, Malé, into a resort metropolis with barely a care for preserving reefs or local livelihoods, has thankfully all but come to a halt.

If the Maldives are a dot on the world map, the island of Hadahaa is a mere grain in an enormous oceanic expanse, as far south as you can go without crossing the equator. It lies in the utterly unspoilt and second largest atoll in the world, Huvadhoo. Until recently the whole area was off limits to visitors, the result of a government policy that sought to protect its ecosystem but also discouraged mingling between tourists and the local population, which put many travellers off these islands because they felt them to be a cultural void.

Since 2007 a small clutch of hotels has been allowed to set up among the native islands under the strictest environmental supervision, bringing employment and visitors to a region previously ignored. The contrast between this gloriously underpopulated, development-free atoll and the frenzy of the resort scene around Malé is extraordinary.

The latest arrivals, such as the one I'm visiting, pay more than lip service to environmental concerns. At Alila Hadahaa, which opened in August, they have their own desalination plant to create drinking water, hold a Green Globe Certification for planning and construction, and use wood certified sustainable from Malaysia. Most commendable of all is the presence of so many local staff; Maldivians make up 65% of the workforce. For a people in search of a homeland â€“ as their president has described them â€“ they couldn't be doing a better job of the audition. Staff such as Atheef â€“ in his roving role of villa butler â€“ and Shamin (snorkeller, babysitter, football expert and purveyor of popcorn) are proud of their country, eager to help you to experience more of it and so good with the kids that I feel surplus to requirements.

For a resort so clearly not imagined with children in mind â€“ from the lavish luxury of the super-chic rooms to the glass and stone-hewn bathrooms â€“ they couldn't cater for them better. Chicken curry sans spices, jelly made to order, babysitting on request and everywhere waiters happy to build "volcano land" in the sand, dive masters who long to take them snorkelling. I virtually have to wrestle the staff to get the children back for a couple of hours a day.

Alila's new resort is certainly architecturally adventurous. The two-storey state-of-the-art restaurant with its Bauhaus severity is slightly wasted on an ageing barefoot boho like myself, but the luxury beach bungalows and water villas make it a positively elemental experience. Of course it's an irony that is hard for the arriving tourist to ignore that the popular wooden water bungalows strung out on stilts above the aquamarine shallows at most resorts could, in the course of our children's lifetime, be all that's left of this island nation.

FOR THOSE WHO stray as far south as Hadahaa, the reward is a pewter evening ocean with a hazy shadow of islands on the far horizon, bearing no sign of human habitation. Ears pump with the complete silence we so rarely get to hear. When I take my four-year-old son snorkelling 5ft off the beach and find a lionfish swaying in the swell, a couple of Moorish Idols guarding the reef and as many small yellowtails as I can count, Dan starts to choke on his snorkel in excitement. To say the ocean is still stocked biblically here would be to underestimate what lies below.

Visiting the local villages is also now actively encouraged, as we discover when we are taken on an afternoon trip to Gadhdhoo, where hand-weaving straw tablemats and fishing offer the only alternative employment to the hotel and tourist sector. Despite obvious poverty and very basic amenities, the village looks like it is auditioning for a Best Kept Town award: no rubbish, well-tended homes with immaculate front yards and trees adorned with colourful strips of the Maldivian flag.

Shamin explains that every evening at sunset the women and children take to street cleaning in order to keep their collective home in good order. If only a similar civic spirit could be nurtured in the UK. During our amble around town an elderly lady in a headscarf (since 9/11 the Maldivians, previously relaxed Muslims with a little bit of local magic thrown in, have increasingly been embracing a stricter Islamic code) stops me to enquire whether Molly and Dan are my only children. When I reply that they are, she looks at me pityingly before declaring that she has produced 14. Patting my meagre contribution to the population on their heads, she wanders off chuckling in amusement at my uselessness as a woman.

This is my fourth trip to the Maldives and the first where I get to meet local people in their own environment and also to eat their cuisine. Along with western delights that include breakfast croissants the finest Parisian pastry chef would be proud of, Alila Hadahaa boasts a local restaurant â€“ sand-floored, trestle-tabled and musically themed â€“ offering the spiciest of curries, the tastiest of pumpkins, the crunchiest papaya and chilli salads on poppadoms, and pancakes with caramel bananas or fresh coconut rice pudding to follow. Where other Maldivian resorts can seem hell bent on ignoring their surroundings, this one is utterly committed to celebrating them.

On our last night, as the great fiery disc of the sun begins its exhausted slide into the sea, we spot a pod of dolphins gliding in and out of water thick as oil, feeding on the plentifully stocked and carefully protected home reef. The children, who have been weaving coconut-frond tapestries with Shamin, run shrieking toward the ocean, dropping clothes along the powder-white sand as they race into the sea in pursuit of each other. The dolphins make a hasty exit to open water, but in their absence a familiar figure steps into the frame: Shamin, waist deep in the ocean, still in uniform shorts and polo shirt, initiating a game with the kids.

It's my abiding image of our brief sojourn on this entrancing island. Thanks not to the cutting-edge design of the resort nor the fantastic food but to the seductive charm of the local staff, the five nights here number among the best vacations of my life.

HOW TO GET THERE... Elegant Resorts (01244 897 515; elegantresorts.co.uk) is offering seven nights at Alila Villas Hadahaa for the price of five, from £2,280 per adult, £2,070 per child (based on four sharing), including breakfast, British Airways flights and all transfers.

Visit guardian.co.uk/travel for more advice and travel suggestions

CARBON NEUTRAL... BUT WHAT ABOUT THE FLIGHTS?

The Maldives is engaged in an ambitious plan to become the world's first carbon-neutral country. By 2020 all its power will come from the wind and the sun, plus a biomass plant burning coconut husks. But the Maldives' biggest industry is tourism, so what about all the carbon emitted by the flights? There is no magic solution, but the government's plans include offsetting the emissions of all flights. Several offsetting methods are being examined, including buying "European emissions permits" which reduce pollution from Europe's factories. Until the scheme is operational, tourists have to arrange their own offsets. Mariella Frostrup did so with Climate Care (jpmorgan climatecare.com).

Maldives

Mariella Frostrup guardian.co.uk © Guardian News & Media Limited 2010 | Use of this content is subject to our Terms & Conditions | More Feeds

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'A sandwich with your nose job?'

Guardian Unlimited

- 23 hours and 52 minutes ago

Lunch-hour cosmetic surgery â€“ 45-minute boob jabs, nonsurgical rhinoplasty â€“ is booming in the UK. But nightmare stories are also on the rise. So are the treatments safe? We speak to doctors to find out, and take a front-row seat at a no-frills nose job

Cosmetic surgery is changing. One advancement is the use of twilight surgery, where they send you only half to sleep. Clinics are alive with dazed facelift patients, who keep their eyes open, frowning and smiling on demand, who come to after the sedation's worn off, their skin tight but bruised, able to remember nothing of the knife at all. There are other patients who trip in off the street for a half-hour boob job under local anaesthetic, and still more who book a session of Botox in their lunch-breaks. The current excitement, in plastics, is not in the perfection of a newly sculpted nose but in the speed at which patients can recover, and the market for these fast, temporary procedures is growing wildly.

The Knightsbridge Laser Clinic is one of many that has recently started promising lunch-hour transformations, offering laser lipolysis to eliminate fat, the G-spot injection to enhance sexual stimulation, Macrolane breast injections, nonsurgical rhinoplasty and Botox fillers to remove wrinkles. A block away from Harrods, I climb their carpeted stairs to the waiting room as the lunch-time rush subsides. Outside a light rain is falling, and the smell of a wet fur coat, woody and dead, hangs in the air of the clinic's small landing. Its owner brushes past me, straight into one of three white and well-lit offices. In a corner room, beside a sheeted bed, I soon take my seat, an audience of one at a 15-minute nose job.

The patient, a young, elegant woman with jewelled shoes, had rhinoplasty in Harley Street as a teenager but now wants it still straighter. Her first operation, which cost £8,000 and required a week in hospital, had left her with a smaller nose, she says, but slightly wonky nostrils. "You might not notice it," she says apologetically, "but I do."

The doctor, Salinda Johnson, a slight and surgically tweaked woman who studied cosmetic dermatology in Thailand, warns of the possible side-effects of today's procedure as she applies a numbing cream to the patient's face. "Soreness, redness, bruising," she chants, "which will settle down within two weeks and break down completely within a year." Johnson rereads the patient's notes and holds up a pink-nailed hand. "There is a problem â€“ we can't do the procedure on a pregnant woman." Her nose glossy with anaesthetising cream, the patient exchanges hurried words with the doctor, and I look pointedly out of the window. An unwanted pregnancy. A sense that the risk is welcome. Minutes later, she is gone.

"Don't worry!" the doctor chirps. "We'll show you the procedure on our receptionist!" Diane has worked at the clinic for four months and, at 23, has already had Botox to fill in a frown line between her brows. Her nose is small and straight, but she has self-diagnosed â€“ she feels there's a dent. She asks the doctor if she thinks rhinoplasty's necessary. "Nothing is necessary," Johnson says, applying the numbing cream. "So can you do my lips, too?" Diane asks, pouting. Johnson shows me the syringe, prefilled with a mixture of anaesthetic and Restylane filler, a hyaluronic acid. The needle is long, and she pushes it firmly into Diane's nose before using both hands to massage the filler into place. The air-conditioning system screams on, and dies just as quickly â€“ the only sounds are Johnson's gloves, baggy on her tiny hands, squeaking.

I gather myself. Does it hurt, I ask Diane, who's breathing calmly, her fingers gently worrying the sleeve of her sweater. "No, I can't feel anything. I can just smell the rubber gloves." Were you interested in getting cosmetic surgery before coming to work here? "No!" she says, through the doctor's fingers, her nose changing shape, delicately, before my squinting eyes. "But I see so many people coming in at lunch time and leaving looking... fresher, and you can't even tell what they've had done. So I had laser hair removal, which feels like being slapped, and Botox, which was really nothing, and then I saw that you could make your lips look more defined with filler, so I've been pestering Salinda to do me."

Dr Johnson wipes around Diane's mouth with a small antiseptic cloth, and warns her that, on a pain scale, this will hurt a seven. She injects Restylane into the lips, and Diane's eyes flicker backwards. With her fingers, Johnson pushes the filler into a cupid's bow â€“ the effect is that of a mother wiping chocolate smears off a child's mouth.

The Harley Medical Group, the UK's largest cosmetic surgery provider, published figures in January revealing the nonsurgical cosmetic surgery market (which includes the Macrolane boob jab, an injection that increases your bust size, and Restylane rhinoplasty, the injection that straightens your nose) saw continued growth in 2009, with dermal fillers and chemical peels driving the increase by 26% and 306% respectively. Last year also saw a continued rise in the number of male patients (up 5%), with "Boytox" (male Botox) and "Sweatox" (anti-sweat Botox) both contributing to the leap.

"Minimally invasive procedures rule today â€“ and this is what consumers, and especially men, want most," says Wendy Lewis, independent cosmetic surgery consultant and author of Plastic Makes Perfect. "The benefits for consumers are: subtle improvements over time; nothing radical; less risky; definitely cheaper than big surgeries; no need for anaesthetic or going to hospital and catching MRSA; and no scars."

"There are many reasons why day surgery is becoming more and more popular," Dr Johnson tells me after Diane has floated back to her desk, swollen but smiling. "People who thought they didn't want to get surgery because they were not brave enough, or not rich enough, are interested in these temporary and non-expensive procedures â€“ our nonsurgical rhinoplasty starts at £350. And it's so quick! The talking takes longer than the treatment. We have a lot of clients who work at Harrods and really do just pop in on their lunch breaks."

The market continues to swell, imperceptibly smoothing the faces of colleagues, relatives, local hairdressers. A study carried out for the Girl Guides last November found almost half of secondary school girls said they planned to have plastic surgery. "Girls and young women are telling us that they are finding it quite hard to accept their appearance, and it is starting at a much earlier age than we had previously thought," says Nicola Grinstead, a trustee of Girlguiding UK. "The survey shows girls as young as 11 are dissatisfied with how they look and are prepared to use surgery to make a change."

All the women I talk to in the clinic's waiting room flicking through OK! magazines agree that today Botox, and increasingly cosmetic surgery, really is "no big deal". They nod, eyes wide, and reel off names like a BBC3 news bulletin. Last year Kylie Minogue, Geri Halliwell, Jennifer Aniston and Courtney Cox all gave interviews about their Botox use, while a film critic compared Nicole Kidman's facial skin to melamine. This month Cheryl Cole was photographed walking through a London airport with lips like salted slugs, and reality star Heidi Montag, 23, underwent 10 procedures in one day and ended up looking just like lingerie model Caprice, who is 38.

In a culture that celebrates youth, the appeal of an injection that appears to shave a little time off your age is clear, especially for the famous and often-photographed. As the demand for surgery has grown, academics have increasingly discussed the democratisation of beauty. If everybody could, in the space of a lunch hour, become symmetrical and clear-skinned, would the power of prettiness be weakened? If we accept that we will be judged on our appearance, is the fact that we can control it almost liberating?

Two years ago, Observer beauty journalist Alice Hart-Davis was one of the first women in the country to try the Macrolane breast enhancement jab. "I had never seriously considered having a proper breast enhancement. I don't feel surgery is something to be undertaken lightly," she tells me. "But I've always wished there was something I could do to boost my bust just a bit that didn't involve surgery."

Macrolane, which arrived in the UK in 2008, is a gel filler which is injected into the breast with a long blunt needle. It increases the bust by one cup size, lasts a year and costs around £2,000. "The procedure was amazing," says Hart-Davis, "an instant result. I was beyond thrilled with it." Though clinics advertise boob jabs in their list of lunch-time treatments, and the injections are over in 10 minutes, she warns: "It's by no means a 'lunch-hour lift' type procedure; it doesn't take long, but I reacted strongly to the local anaesthetic: it didn't hurt, but I could hardly speak straight for the rest of the day. And your body and brain go into a kind of post-traumatic shock after any procedure like this. You need to take it quietly afterwards."

Three months after her injections, one breast deflated â€“ she settled for stuffing her bra with a sock â€“ and the other went rock hard. Her surgeon broke up the gel under anaesthetic, then injected more to balance her bra. A few weeks later, she felt a lump in her right breast. She panicked and returned to the doctor, who reassured her that it was nothing to worry about â€“ just a lump of hardened gel. "That experience," she concludes, "alongside discovering that the research conducted on the product was not half as extensive as I'd been led to believe, and talking to several surgeons who strongly disapprove of the procedure, has put me off trying it again."

One such surgeon is Mr Charles Nduka, who runs the not-for-profit patient information website safercosmeticsurgery.co.uk. "There's so much misleading information being published about 'lunch-time' procedures," he says, "leading, at best, to unrealistic expectations and disappointment and, at worst, complications. Facial procedures such as Botox may leave localised swelling, redness and in some cases bruising, even in the best hands. This means that if you wanted to keep your treatment secret, lunch time may not be the best time.

"A major issue in the UK," he continues, "is that because fillers are classified as medical devices â€“ the same as implants â€“ rather than drugs, the regulations about who can administer them are among the most lax in the developed world. The recently introduced guidance from the Ihas [Independent Healthcare Advisory Services] is a mockery. It's a system of self-regulation which means that the very practitioners who should be regulated will not sign up. There have been more than 100 fillers introduced in the UK and in many cases they were withdrawn due to side-effects. Essentially the UK becomes a testing ground for new products."

So would he recommend traditional plastic surgery over the lunch-hour treatments? "Few people have social lives so hectic that they cannot give themselves the luxury of having a treatment in an unrushed fashion," Mr Nduka says, "without the anxiety that swelling might show."

Dr Mike Cummins, a GP and cosmetic surgeon who, after requests from patients, agreed to carry out group treatments at Botox parties, agrees that the "lunch-time" label can be misleading, but says that as doctors' experience of anaesthetics increases, "there continue to be more and more advantages to daycare procedures, both for the patient and the client. Laser-assisted liposuction is getting to the point where it's more than reasonable to do it under twilight sedation and cosmetic surgeons are all working to get the least trauma to tissue under local anaesthetic as possible."

In Jeanette Winterson's novel The Stone Gods, published in 2008 but set in a futuristic dystopia, people alter their genes to preserve their youth and get plastic surgery to amplify what's left. Only the protagonist, Billie, chooses to age naturally, wrinkling slowly among the smooth foreheads and perky breasts. Winterson worries about the normalisation of cosmetic surgery. "What really bothers me," she says, "is that women used to be made to believe that their minds were inadequate, but we were allowed our bodies. Now that we can't be told our minds aren't up to it, our bodies are paraded as defective. It is the same old control. It is not just an assault on women â€“ it is a war on feminism."

She emails me later that day. "I find 'lunch-hour surgery' savage and cynical. An insecure woman is a woman who will pay to feel better about herself. Disguising insecurity and feelings of inadequacy as empowerment is part of the usual twisted message of consumer advertising, but where women are concerned the strategy asks us to fund our own oppression. We pay to feel better instead of asking why we are made to feel defective in the first place... We need to understand that what is happening to women now is part of a disturbing bigger picture and not just a question of: 'Does madam fancy a nose job?'"

How does Winterson see society progressing in this era of perfectibility? Does she predict new lows, new depths? "We'll all get fixed eventually. Parents will do it to their kids. It will become routine. The Stepford Wives world of the 1950s was made impossible by feminism. We are heading back that way by another route. Women made in the image of men."

After Diane's 15-minute nose job, I take a walk through Harrods' beauty hall. I feel a little drunk. I had gone into the clinic expecting gore, or at least tears, but I left shocked only at the dry eyes, lack of fuss, the ease, the speed and gentle effectiveness. The women in Harrods testing the perfumes are largely blondes, largely wrinkleless, and largely slim. I see three people who look like Caprice, but as reflected in varying fairground mirrors. I watch a mother pick out scented candles for her granddaughter's wedding reception, and admire her shiny still forehead as she quietly exclaims over jasmine perfumes. I'm suddenly aware, looking discreetly from face to face, of all the "work" done and all the work yet to be done. It is an awakening of sorts. A half-awakening, maybe, to an odd new twilight world.

QUICK FIXES The most popular nonsurgical procedures

MACROLANE: BOOB JAB Created by Q-Med, the Swedish company behind the wrinkle-filler Restylane, Macrolane was launched in Europe as a correctional filler for body indentations. It wasn't until it was used in Japan in 2004 that it took off as an alternative for breast implants â€“ by January 2008, when it launched in the UK, about 30,000 Japanese women had had the boob jab. The procedure, which takes 45 minutes, involves a gel filler made of hyaluronic acid being pumped into the breast through a flexible knitting needle-sized canula. PRICES from £1,800

RESTYLANE: NOSE JOB Restylane, a water-based filler, is a synthetic reproduction of hyaluronic acid, a substance found in living organisms. Until recently its main use has been to plump lips and fill crow's feet, but the new procedure involves injecting the bridge of the nose to fill in dents, and the tip, so it appears perkier. Effects wear off within 18 months. PRICES from £350

BOTOX An injection of Botulinum toxin A (a diluted and purified form of the bacteria which causes botulism) softens and prevents frown lines. The jab, 22 years old this spring, changed the face of cosmetic surgery, with celebrities including Simon Cowell admitting to relying on it to look younger. Each year it is estimated to make its manufacturers around £800m from more than 60,000 injections. PRICES £230 to £390

JUVEDERM: LIP ENHANCEMENT A series of injections of Juvederm filler around the mouth can make the lips fuller and reshape ageing pouts. Juvederm contains hyaluronic acid which, by attracting water, plumps up the skin. Results last for up to a year. PRICES from £250

guardian.co.uk © Guardian News & Media Limited 2010 | Use of this content is subject to our Terms & Conditions | More Feeds

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Treasury calls in Cable for talks about hung parliament

Guardian Unlimited

- 23 hours and 53 minutes ago

· Liberal Democrat 'ready to be chancellor'
· Whitehall mandarins prepare for coalition

Vince Cable has held unprecedented and detailed talks with the top official at the Treasury about the Liberal Democrats' economic policies â€“ and declared himself willing to serve as chancellor after the next election.

As Whitehall gears up for a possible hung parliament, Cable told the Observer that he had been questioned by Nicholas Macpherson, the Treasury's permanent secretary, about what the Lib Dems' demands would be in a coalition with Labour or the Tories.

Cable was unaware of such meetings having taken place with Lib Dem shadow chancellors before previous general elections. The talks were a sign that the Treasury was "taking seriously" the prospect of his party playing a leading role in economic policy in what could be the first hung parliament since 1974.

"He wanted to know what we attached priority to. He wanted to know what we felt strongly about," Cable said, adding that his ideas on tax and spending were well received. He didn't say to me: 'Yes, minister, but you can't do that'."

Cable, whose credibility has grown throughout the economic crisis, made clear that, if he was to be offered the chancellorship in a hung parliament, he would jump at the chance. He did not want to be "the most unpopular person in Britain" as public spending is slashed, he said, but added: "I wouldn't be in this business if I wasn't willing to take the responsibility if it was to come my way."

It comes as two more opinion polls point to a hung parliament. An ICM survey for the News of the World puts the Tories six points ahead on 38%, and research by YouGov for the Sunday Times suggested the party enjoyed a seven-point advantage.

David Cameron and his shadow cabinet have already held talks with senior Whitehall mandarins in preparation for a likely handover of power. But talks with a third party take place only where there is a serious prospect of it holding the balance of power.

Downing Street and the Treasury said Alistair Darling would present a "budget for growth" on Wednesday, portraying Labour as the party to nurse the economy back to health, with investment in jobs and industry, and warning that the Conservatives would jeopardise that with premature spending cuts.

The chancellor has little room for manoeuvre in pre-election giveaways, but one idea being seriously considered is to delay a 3p rise in petrol duty. Darling will announce a £1bn green infrastructure fund to invest in low-carbon technology and extend job schemes to help unemployed young people into work.

While the deficit is expected to be as much as £10bn below the £178bn forecast in his December pre-budget report, the Treasury stresses the focus will be on the chancellor's commitment to halve the deficit within four years. "It's a boring budget," said a No 10 source. "He may extend the odd payment here and there, but it is about stability and jobs."

In his weekly podcast, Gordon Brown states today that the recovery remains "fragile and in its infancy". The prime minister says that Labour's commitment to cut the deficit is "non-negotiable", but stresses that investing in jobs and programmes for industry is a way to reduce it in the medium term.

"It means not taking away the extra support too soon, which risks setting back the recovery and tipping us back into recession... If we allow unemployment to run riot, as happened in previous recessions, that will cost us more and add to the deficit," he says.

Cable made clear he would have serious reservations about working with either Labour or the Conservatives. "I'm worried about both," he said. "If either of them came back, Gordon, given his history, will be in denial about difficult decisions, and the Tories are in danger of doing foolish, precipitate things that could make the situation a lot worse."

Cable was noticeably more critical of the Conservatives' response to the financial crisis, saying that they should score "nul points" for failing to grasp the seriousness of the situation. "They haven't done anything to attract praise, because they completely and totally misunderstood the problems."

By contrast, Labour had had a "purple passage" in the autumn of 2008, when Brown led international efforts to recapitalise the banking sector after the collapse of Lehman Brothers.

The Conservatives sought to seize the initiative on reforming the bloated financial sector this weekend, promising to implement a US-style tax on banks if they win the general election, instead of waiting for an international consensus to emerge, as Labour has promised to do. Cameron spelled out the measure in a speech about taking on the "vested interests" in society, comparing the battle to constrain the banks today with Margaret Thatcher's attack on union powers in the 1980s.

Lord Myners, the City minister, said: "This ill-thought-out Tory briefing has all the hallmarks of a plan made up on the hoof."

Toby Helm Heather Stewart guardian.co.uk © Guardian News & Media Limited 2010 | Use of this content is subject to our Terms & Conditions | More Feeds

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Obtenir rapidement un aperçu sous Windows 7 (Memoclic)

St. Mary's stuns Villanova for berth in Sweet 16

Top 10 Twitter Trends This Week [CHART]

Mashable!

- 1 days and 3 hours ago

Justin Bieber remains an immutable force of Twitter trend power, taking the top slot again for the third week in a row. Tweeters also showed their love (and/or disdain) for a number of other pop singers, and celebrated a few holidays this past week.

Thanks to our friends at What The Trend, we have yet another interesting stats-eye-view of the Twitterverse. Because this is a topical list, hashtag memes and games have been omitted from the chart below.

Beyond Justin Bieber, Follow Friday, and Music Monday — the reigning trend champs — St. Patrick’s Day made an appearance as people tweeted their revelry, and Lady Gaga crept up on the list with the premiere of her new video on Vevo and a tour in New Zealand.

The Jonas Brothers hung tight near the middle, while circle enthusiasts everywhere tweeted vigorously about Pi Day on March 14th, spurred on no doubt by the charming Google doodle that commemorated the occasion.

If you own a TV or computer, you probably know that March Madness is upon us, and bracket-related tweets have been flying around the web all week, landing the term at number seven.

Rounding out the chart are two more singers who made some news this week. Demi Lovato, the 17 year old actress/singer, stirred some buzz with her admission that she’s dating a Jonas Brother, and Chris Brown, the career-stunted R&B singer, reached out to his fans on the web for some help on making a comeback.

Strangely, tweets about the ongoing South By Southwest (SXSW) conference — one of the most talked about topics in tech and a favorite of the Twitter community — did not reach critical mass to make this week’s list. This is likely due to the lack of big announcements or product launches from the conference this year.

You can check past Twitter trends in our Top Twitter Topics section as well as read more about this past week’s trends on What The Trend.

Top Twitter Trends This Week 3/13 – 3/19
RankTopicTop Index This WeekChangeDescription#1Justin Bieber1Justin Bieber’s new album My World 2.0 comes out on March 23rd & his fans are excited. He also appeared on Z100.com, QVC, and GMTV in the UK.#2Follow Friday1Follow Friday is a tradition where people tweet people they believe are fun/interesting to follow (on Fridays).#3St. Patrick’s Day2NEWPeople are tweeting "Happy St. Patrick’s Day" and showing their Irish spirit.#4Lady GaGa22Lady GaGa is currently touring in New Zealand.#5Music Monday2Music Monday is a tradition where users recommend music they appreciate every Monday.#6Jonas Brothers7Mentions of the Jonas Brothers.#7March Madness1The National Collegiate Athletic Association’s Division 1 Men’s Basketball tournament started this week.#8Happy Pi Day2NEWMarch 14th is Happy Pi Day! Pi is, roughly, 3.14. And today is 3/14. And March 14 is also the birthday of Albert Einstein#9Demi Lovato3March 13 2010, "Jemi" is confirmed. Demi Lovato admitted to dating Joe Jonas in an interview by Billy Bush. Many people are tweeting their opinions about this new couple. Joe Jonas and Demi also recently released a new song, "Make a Wave."#10Chris Brown1NEWSinger Chris Brown asked his fans to help revive his
career. They have been obliging with a variety of trends.

Tags: justin bieber, Top Twitter Topics, trends, twitter, twitter trends, What The Trend

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“Damas de Blanco:” A Week of Protest in Cuba

Global Voices Online

- 1 days and 6 hours ago

To the extent that the Castro brothers are, as Blog for Cuba writes, “afraid of women wearing white,” it's due to more than just the uniform color of their outfits or their weekly marches through Old Havana.

The Damas de Blanco (Ladies wearing White) protests come on the heels of a flutter of international condemnation incited by the hunger striker Orlando Zapata Tamayo's death last month:Â an official resolution was passed in the European Parliament, and a petition calling for the immediate release of all political prisoners that was posted to a blog less than a week ago has already been signed by Spanish director Pedro Almodovar and Peruvian writer Mario Vargas Llosa. Meanwhile, yet another hunger striker is hospitalized in Havana after refusing asylum.

Wednesday's crackdown by Cuban police was the first in two years on the political group, which is made up of the daughters, wives and mothers of imprisoned political dissidents.Â They're commemorating the seventh anniversary of 2003's “Black Spring,” in which 75 dissidents were arrested, by marching every day in the Cuban capital.Â Â In the most violent of the reactions to these protests, the women were reportedly attacked by a mob of pro-government Cubans and forced onto a bus by authorities.

We are protesting peacefully and we are not going to get on the bus of a government that has kept our family members in prison for seven years…

said the group leader, Laura Pollán, just before she was forced off the street and onto the bus. Repeating Islands quotes an AFP report, saying:

As police were taking the women away, Margarita Rodríguez, a housewife in a crowd of some 300 pro-government demonstrators, shouted: ‘Board them by force, it’s what they deserve. This is a provocation.'

This was the least of the slurs directed at the Ladies in White by the Castro supporters who flanked the marchers and pushed them towards the bus. In reaction to the violent antagonism among Cubans of different political viewpoints, Yoani Sanchez writes:

I shudder to imagine a Cuba where physical â€“ and legal â€“ attacks against people, for their political affiliation or ideological leanings, continue. What a sad country we will have if the authorities continue to consider it normal to ‘teach a good lesson' to anyone who contradicts the official viewpoint. To me, a society that passively stands by as peaceful women with gladioli in their hands are bullied, as happened yesterday, is quite sick.

At Havana Times, Yusimi Rodriguez recounts turning a corner in Old Havana and realizing that this was not your everyday “Damas” march:

Coming down the street was a group of approximately twenty women dressed in civilian clothing and chanting slogans. Â Around them flocked several reporters filming and taking pictures. Â I suppose these were mainly or entirely foreign reporters.

At first I didn’t know what was happening until somebody told me it was about the Ladies in White. But none of the women I saw were wearing white, nor could I understand the first slogans they chanted. Â But suddenly, at the closest spot I could reach, they began to shout, ‘Whoever doesn’t jump is a Yankee'…The women in the demonstration itself did indeed jump. Â One even ran forward jumping with her two feet at the same time. Â Finally that group went by and I was able to see â€”for the first time since I’d heard of themâ€” the Ladies in White: a group of between fifteen and twenty women dressed in white. They all proceeded in silence and carried gladiola flowers. Around them were several uniformed police.

Rodriguez also notes the marked organization of the anti-government protesters:

I find it striking that these community women, who are not police or agents, have been able to become organized so well and interrupt the Ladies in White so quickly.Â Could it be that they all come from the same neighborhood?Â How did they find out about the march?Â Â Was it publicized?Â I was also surprised they were only women. Undoubtedly it would have looked very bad if men had faced up to the Ladies, especially if it was true that there was some pushing and shoving in the heat of moment, as someone said.Â Between women it’s something else, there are more equal conditions. Â Both sides were made up only of women: those from the community and the Ladies in White (who, by the way, are also Cuban women and therefore part of the broader Cuban community).

“One thing is clear these manifestations against the ladies in white at clearly organized by the regime,” writes Julio de la YnceraÂ in a comment at Havana Times.

On Wednesday night, Cuban television aired a round table discussion about implicating international meddlers in the domestic unrest.Â In this case, the government may be more on target than it would like: as bloggers and other online activists are showing, anger over human rights abuses within (and without) the island is swelling, and more people are watching to see what will happen next.

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Subretinal implant successfully tested on humans, makes blind narrowly see

Chemiresistor sensors array optimization by using the method of coupled statistical techniques and its application as an electronic nose for some organic vapors recognition

Detection of vapours and odours from a multisensor array using pattern-recognition techniques Part 2. Artificial neural networks

CiteULike: Borelli's watchlist

- 1 days and 11 hours ago

Sensors and Actuators B: Chemical, Vol. 9, No. 1. (July 1992), pp. 9-15.

Considerable interest has recently arisen in the use of arrays of gas sensors together with an associated pattern-recognition technique to identfy vapours and odours. The performance of the pattern-recognition technique depends upon the choice of parametric expression used to define the array output. At present, there is no generally agreed choice of this parameter for either individual sensors or arrays of sensors. In this paper, we have initially performed a parametric study on experimental data gathered from the response of an array of twelve tin oxide gas sensors to five alcohols and three beers. Five parametric expressions of sensor response are used to characterize the array output, namely, fractional conductance change, relative conductance, log of conductance change and normalized versions of the last two expressions. Secondly, we have applied the technique of artificial neural networks (ANNs) to our preprocessed data. The Rumelhart back-propagation technique is used to train all networks. We find that nearly all of our ANNs can correctly identify all the alcohols using our array of twelve tin oxide sensors and so we use the total sum of squared network errors to determine their relative performance. It is found that the lowest network error occurs for the response parameter defined as the fractional change in conductance, with a value of 1.3 Ã— 10 âˆ’4 , which is almost half that for the relative conductance. The normalized procedure is also found to improve network performance and so is worthwhile. The optimal network for our data-set is found to contain a single hidden layer of seven elements with a learning rate of 1.0 and momentum term of 0.7, rather than the values of 0.9 and 0.6 recommended by Rumelhart and McClelland, respectively. For this network, the largest output error is less than 0.1. We find that this network outperforms principal-component and cluster analyses (discussed in Part 1) by identifying similar beer odours and offers considerable benefit in its ability to cope with non-linear and highly correlated data.
JW Gardner, EL Hines, HC Tang

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6,1,3,7,2

Stardock CEO going on modding sabbatical after Elemental ships

Best Of Indie Games: Cut, Copy, Paste, Profit

GameSetWatch

- 1 days and 15 hours ago

[Every week, IndieGames.com: The Weblog co-editor Tim W. will be summing up some of the top free-to-download and commercial indie games from the last seven days on his sister 'state of indie' weblog.]

This week on 'Best Of Indie Games', we take a look at some of the top independent PC Flash/downloadable titles released over this last week.

The goodies in this edition include a 2D platformer with a clever copy and paste gimmick, a 2D action game where you attack enemies by commiting suicide, a one-button effort about the adventures of a fish with a human-like face, and an action RPG where the characters are depicted as circular dots.

Here's the highlights from the last seven days:

Game Pick: 'Jump, Copy, Paste' (Arvi Teikari, freeware)
"Jump, Copy, Paste is a 2D platformer in which you overcome obstacles by copy and pasting parts of a level to build new platforms or create a passage through a wall. Parts which are greyed out cannot be affected by your copy and paste ability, so players need to work around those areas as they collect all yellow pieces to unlock the exit door."

Game Pick: 'Siromaru' (Abaruzu, commercial indie - demo available)
"Shiromaru is a 2D action game in which you attack enemies by commiting suicide and causing a chain of explosions. The longer the chain reaction, the more extra life items appear for you to collect."

Game Pick: 'Tiny and Big' (Black Pants Studio, commercial indie - demo available)
"Tiny and Big tells the story of a thief who had stolen our hero's most valued possession - a pair of underpants. The game basically is about him trying to chase after Mr. Big who had escaped to the top of a tall mountain. Armed with a raygun and a grappling hook, you must cut pillars and solid rock to build yourself platforms to stand or jump on."

Game Pick: 'Fish Face' (Beau Blyth, freeware)
"Fish Face is a one-button arcade game with three levels to play, each taking roughly five to ten minutes to complete. Here you play as a fish that uses its buoyancy to move in and out of the water, avoiding walls or enemies that will hurt our aquatic friend on impact."

Game Pick: 'Dragondot' (Nathan McCoy, browser)
"Dragondot is an action RPG in which you play as a dragon that can only claw at its adversaries at first, but will gain new and improved abilities whenever it gains enough experience to level up."

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BBC Seven Ages of Britain - Age of Power 1x3 [HDTV - MVGROUP]

Relationship Between Potentially Modifiable Lifestyle Factors and Risk of Second Primary Contralateral Breast Cancer Among Women Diagnosed With Estrogen Receptor-Positive Invasive Breast Cancer

CiteULike: Borelli's watchlist

- 1 days and 17 hours ago

J Clin Oncol In J Clin Oncol, Vol. 27, No. 32. (10 November 2009), pp. 5312-5318.

PurposeAn outcome of considerable concern among breast cancer survivors is the development of second primary breast cancer. However, evidence regarding how potentially modifiable lifestyle factors modulate second breast cancer risk is limited. We evaluated the relationships between obesity, alcohol consumption, and smoking on risk of second primary invasive contralateral breast cancer among breast cancer survivors. MethodsUtilizing a population-based nested case-control study design, we enrolled 365 patients diagnosed with an estrogen receptor-positive (ER+) first primary invasive breast cancer and a second primary contralateral invasive breast cancer, and 726 matched controls diagnosed with only an ER+ first primary invasive breast cancer. Obesity, alcohol use, and smoking data were ascertained from medical record reviews and participant interviews. Using conditional logistic regression we evaluated associations between these three exposures and second primary contralateral breast cancer risk. ResultsObesity, consumption of [≥] 7 alcoholic beverages per week, and current smoking were all positively related to risk of contralateral breast cancer (odds ratio [OR], 1.4; 95% CI, 1.0 to 2.1; OR, 1.9; 95% CI, 1.1 to 3.2; and OR, 2.2; 95% CI, 1.2 to 4.0, respectively). Compared with women who consumed fewer than seven alcoholic beverages per week and were never or former smokers, women who consumed [≥] 7 drinks per week and were current smokers had a 7.2-fold (95% CI, 1.9 to 26.5) elevated risk of contralateral breast cancer. ConclusionOur population-based study adds to the limited available literature and suggests that obesity, smoking, and alcohol consumption influence contralateral breast cancer risk, affording breast cancer survivors three means of potentially reducing this risk. 10.1200/JCO.2009.23.1597
Christopher Li, Janet Daling, Peggy Porter, Mei-Tzu Tang, Kathleen Malone

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4,1,3,7,2

BBC Seven Ages of Britain - Age of Power 1x3

The Fascinating Story of Cecil DeMille's Lost City

Cinematical

- 1 days and 20 hours ago

Hollywood has a sad history of lost props and costumes. On one hand, you can't blame them. Who can predict what is going to become iconic? Why not reuse that pretty white dress from The Seven Year Itch? But then there are unforgivable examples. The Wizard of Oz was pretty iconic by the time MGM decided to do a garage sale of props, and pieces of history (such as the Lion's suit) flew out the door for pennies. Even when plucky individuals like Debbie Reynolds have tried to set up some kind of museum or preservation group, no one is interested in funding it. Movie history, like so much "real" history, is unappreciated by those with the money to study it. So, The LA Times' story about the lost set of Cecil B. DeMille's 1928 The Ten Commandments isn't at all surprising, but Peter Brosnan's quest to find it is pretty fascinating.

DeMille filmed his original Ten Commandments in the scorching Guadalupe-Nipomo dunes of Santa Barbara, California. As old film buffs know, it was a popular location to film anything that needed a desert sequence until the mid 1940s, when films began shooting on location. There are a few remnants of Gudalupe's glory days kicking around the town, but none so weird and creepy as DeMille's Art Deco Commandments set, which is buried somewhere under the dunes. Pieces of it have popped up from time to time and decorated the town, but the majority of it is still lying in the trench DeMille bulldozed it into.

Brosnan has been trying to find it for nearly thirty years, but has had no luck securing enough funding. He had hoped to film a documentary about DeMille's lost city, but unable to truly dig it up, he's decided to change the focus to that of Gudalupe's glittery history in the hopes of helping a struggling town find its economic footing.

Filed under: Classics, Paramount, Fandom, DIY/Filmmaking, Newsstand, Religious

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Lemarinel : Tracker : la renaissance

Planet Libre

- 1 days and 22 hours ago

Tracker est un moteur de recherche local pour votre ordinateur. Il permet d’effectuer des recherches de fichiers, mais aussi dans les fichiers eux même ou encore dans votre courrier électronique.

Ce projet est assez vieux, on parlait de sont inclusion dans le projet Gnome il y à quelques années déjà. Mais à cause de mauvaises performances et d’un développement lent il n’a jamais vraiment pu s’imposer sur le bureau Gnome.

Aujourd’hui c’est d’ailleurs un véritable manque, car aucun réel moteur de recherche n’est implémenté dans Gnome, alors que ce genre de fonctionnalités est maintenant standards ( que ce soit sous KDE, sous Windows Seven ou OSX ).

L’année 2009 à marqué toutefois un réveil du projet, on est ainsi passé de la version 0.5 à 0.7 en un peu plus d’un an et les premiers développements de la nouvelle version 0.8 devraient arriver en 2010.

3 Générations de moteurs de recherches

Pour mieux comprendre la suite de l’article, on va s’arrêter un peu sur les différents types de moteurs de recherches disponibles. Techniquement on peu diviser ces moteurs en 3 générations :

- La première génération ( qui correspond au petit moteur de recherche de fichiers de Gnome ), est un moteur de recherche simple, qui va aller chercher un fichier selon son nom, son type ou sa date de modification. Vous tapez «Â lenomdemonfichierÂ », Et il s’en va le chercher sur votre ordinateur. Dans le meilleur des cas, il est doté d’un cache pour offrir un temps de réponse plus rapide.

Le gros inconvénient de cette première génération, c’est qu’elle est extrêmement limitée. Vous ne pouvez chercher que par le nom du fichier ou son extension. Et si vous ne vous rappelez pas du nom du fichier ou que vous tapez un nom légèrement erroné, vous n’aurez surement aucun résultat pertinent.

De fait ces moteurs de recherches sont peu utilisés. Et on préférera souvent avoir une bonne organisation de l’arborescence des répertoires pour éviter de perdre nos fichiers.

- La seconde génération de moteur de recherche s’est donc attachée à proposer un résultat de recherche un peu plus efficace. Ici il est question de reprendre les fonctionnalités du moteur de 1ere génération, mais en plus de lui permettre d’aller chercher le contenu des informations de chaque fichier ( lorsque c’est pertinent ). Le gros avantage c’est que la recherche devient un peu plus précise. Vous pouvez par exemple facilement retrouver un document texte sur un thème précis, en tapant un mot contenu dans ce document.

Tracker dans sa version stable 0.6.X fait parti des moteurs de seconde génération. Mais la encore la recherche reste peu utile, car le moteur de recherche ne pourra parcourir que le contenu de fichiers lisibles ( documents textes principalement ). Si vous souhaitez chercher d’autres types de documents, comme des images ou des vidéos, vous vous retrouvez donc avec le même problème que le moteur de première génération.

- C’est ici qu’intervient le moteur de recherche de 3éme génération, qui s’appuie sur le bureau sémantique. Le bureau sémantique consiste à construire un réseau d’informations sur l’ensemble des éléments du bureau; que ce soit les médias, les documents, les applications ou tout autre élément pertinent composant l’ordinateur ou son réseau. Pour chaque élément on va garder en base de donnée des informations pertinentes sur son contenu ( par exemple pour une photo l’auteur de la photo, la date de prise, le lieu, la définition... ). Il sera en plus possible d’associer des tags pour chaque élément ( exemple : photos de vacances ), permettant ainsi de regrouper les fichiers sans prendre en compte l’arborescence.

Enfin, pour rendre le système encore plus intelligent,le système créé des liens entre les différents éléments du bureau. Par exemple votre ami «Â PaulÂ » vous envoie les photos de vacances que vous avez passés ensemble. Vous les stockez dans un répertoire. Puis quelques jours plus tard vous souhaitez les voir de nouveau. Il vous suffit de chercher «Â PaulÂ » dans le moteur pour retrouver les fichiers qu’il vous a envoyé. Vous ajoutez le tag «Â Photo de vacancesÂ » et elles se retrouveront dans votre gestionnaire de photos dans la bonne catégorie ( si ce dernier supporte Tracker) .

Tracker 0.7 : le renouveau... expérimental.

Pendant l’année 2009, l’équipe de Tracker à décidé, de refondre totalement le projet. L’objectif est de créer un moteur interne performant, standardisé et facile d’utilisation.

Pour ce faire le projet c’est logiquement orienté vers des standards reconnus.

En premier SPARQL, qui est le langage utilisé pour effectuer des requêtes a la base de donnée de Tracker. SPARQL est un standard défini par la W3C, une des briques du futur web sémantique. Il est officiellement devenu une recommandation en janvier 2008 et permet d’effectuer des requêtes intelligentes en relation avec des documents,images, etc.

La seconde technologie qui fait son entrée dans Tracker s’appel NEPOMUK pour «Â Networked Environment for Personalized, Ontology-based Management of Unified KnowledgeÂ » ou en français : Environnement réseau pour une gestion ontologique personnalisée de la connaissance unifiée.
C’est ni plus ni moins que le standard défini par un projet Européen pour le bureau sémantique que l’on à vu plus haut.

C’est donc avec la version 0.7.X que ces fonctionnalités ont commencés à faire leurs apparitions. De sorte qu’aujourd’hui Tracker propose un moteur de recherche sémantique «Â simpleÂ ». Il manque encore en effet un certain nombre d’éléments comme les liens entre élément, ou plus simplement une meilleure intégration.

Enfin un dernier élément à prendre en compte dans Tracker, s’appel le «Â mineurÂ ». Ce sont des modules qui viennent s’ajouter au moteur principal et qui vont avoir pour rôle d’aller chercher les informations sur des éléments spécifiques. Pour l’instant Tracker dispose de 3 type de «Â mineurÂ » :
- Mineur de fichier, qui va aller chercher la liste des fichiers présents dans votre répertoire personnel et va en extraire le contenu.
- Mineur d’applications, qui récupère le nom et les descriptions des applications présentes sur votre ordinateur
- Le mineur de courrier électronique qui va aller chercher les courrier électronique et leur contenu dans Evolution.

Tracker 0.8 : première version stable

Avec la version 0.8, qui sera la prochaine version stable du moteur et qui devrait officiellement arriver mi 2010, on devrait voir arriver de nouvelles fonctionnalités, notamment de nouveaux mineurs :
- Le mineur rss : qui, comme son nom l’indique, permettra d’aller chercher dans le contenu Rss
- Le mineur internet : qui permettra de garder les informations sur les pages visités et de les retrouver facilement
- D’autres mineurs liéés aux services en lignes (Réseaux sociaux, documents en ligne, etc...)

Enfin le système devrait être encore optimisé vers une meilleure prise en compte des standards de bureau sémantique. Cette version est d’autant plus importante qu’elle pourrait être incluse dans Gnome comme projet officiel. La version 0.7 n’a été accepté qu’a titre de dépendance externe dans gnome 2.30. En cause, l’absence d’une version stable moderne, et le manque de maturité du projet.

Enfin l’équipe de Tracker travail en étroite collaboration avec l’équipe de Zeitgeist. Ce dernier projet permet de garder une trace des actions effectués par l’utilisateur dans le temps, sur les fichiers ou les applications.

Quelques liens :

- Site du projet
- Site du projet sur Gnome
- Blog d’un des développeurs

Billet original de Lemarinel.Votez pour cet article sur le Planet Libre.

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Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves.

Journal of Neuroscience

- 1 days and 22 hours ago

Publication Date: 2010 Mar 17 PMID: 20237282Authors: Ozcelik, M. - Cotter, L. - Jacob, C. - Pereira, J. A. - Relvas, J. B. - Suter, U. - Tricaud, N.Journal: J NeurosciDiameter, organization, and length of the myelin sheath are important determinants of the nerve conduction velocity, but the basic molecular mechanisms that control these parameters are only partially understood. Cell polarization is an essential feature of differentiated cells, and relies on a set of evolutionarily conserved cell polarity proteins. We investigated the molecular nature of myelin sheath polarization in connection with the functional role of the cell polarity protein pals1 (Protein Associated with Lin Seven 1) during peripheral nerve myelin sheath extension. We found that, in regard to epithelial polarity, the Schwann cell outer abaxonal domain represents a basolateral-like domain, while the inner adaxonal domain and Schmidt-Lanterman incisures form an apical-like domain. Silencing of pals1 in myelinating Schwann cells in vivo resulted in a severe reduction of myelin sheath thickness and length. Except for some infoldings, the structure of compact myelin was not fundamentally affected, but cells produced less myelin turns. In addition, pals1 is required for the normal polarized localization of the vesicular markers sec8 and syntaxin4, and for the distribution of E-cadherin and myelin proteins PMP22 and MAG at the plasma membrane. Our data show that the polarity protein pals1 plays an essential role in the radial and longitudinal extension of the myelin sheath, likely involving a functional role in membrane protein trafficking. We conclude that regulation of epithelial-like polarization is a critical determinant of myelin sheath structure and function.post to: CiteULike

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1,journals,majors,regard,sevens

McLaren MP4-12C performance stats have arrived

Chrysler kicks off production of Pentastar V6 engine, formerly known as "Phoenix"

Dust-free quasars in the early Universe.

Media Matters: On health care reform, the Fox News noise machine is cranked to 11

Media Matters for America

- 1 days and 23 hours ago

You know those special amps used by Spinal Tap that go to 11, in order to provide "that extra push over the cliff"? It appears Fox News has gotten a hold of some and hooked them up to its coverage of health care reform.

As the reform bill moved closer to a vote in the House, the Fox News noise machine went into overdrive, hurling every false and misleading claim it could muster.

The week in Fox News health care hysteria began with an oldie-but-goodie -- Steve Doocy, Bill Hemmer, and Bill O'Reilly all claimed or suggested that the bill will, in O'Reilly's words, "require American taxpayers to fund abortion." But it doesn't, at least not beyond what is currently permitted under current law. Fox News, unfortunately, is not alone in repeating this falsehood.

Then, Doocy and Hemmer, joined by Neil Cavuto and several other hosts, jumped on the idea that a legislative procedure the House is reportedly considering to pass the Senate's version of health care reform would allow them to do so without a vote. Wrong again -- the House would need to vote to implement that procedure.

Carl Cameron, however, broke through the noise on this issue, pointing out that the process would simply pass the bill "in one vote instead of two" and that the process "has been used, literally, for centuries" -- indeed, Republicans made copious use of the "self-executing rule" when they controlled Congress. Even Charles Krauthammer conceded that it's constitutional. Still, that didn't keep Alisyn Camerota from scoffing that the rule "might as well be a self-immolating rule."

Fox News then pounced on a survey claiming to have found that 46 percent of primary care physicians would consider leaving their profession if health care reform passes. O'Reilly, Sean Hannity, and contributor Dr. Marc Siegel all portrayed the survey as having been published by the prestigious New England Journal of Medicine.

Except it wasn't. The article was written by the physician-recruiting firm that conducted the survey, and it actually appeared in an employment newsletter produced by the publisher of the New England Journal of Medicine, not the Journal itself. Further, the survey itself was not all that scientific -- done via email contacts taken from the recruiting firm's database -- so any claim that the survey's results accurately reflect the view of the American medical community is dubious at best.

Fox News' Megyn Kelly did eventually note that the survey was "not a scientific poll." But that didn't keep Glenn Beck from insisting -- hours after Kelly corrected the record -- that "The New England Journal of Medicine says that if this bill is passed nearly one-third of doctors will quit practice medicine."

(Beck, meanwhile, is keeping up the long tradition of Fox News hosts pushing partisan political agendas by joining with Republican Rep. Steve King to promote an anti-reform rally in Washington.)

Fox News contributor and serial misleader Dana Perino made her own non-contribution to the health care debate, asserting that the reform bill's Medicare investment tax on those making over $200,000 a year is "so disturbing ... because the people who make that money are the small business owners." In fact, fewer than 1.3 percent of small business owners would be affected by the tax.

When the Congressional Budget Office released new numbers detailing how the reform bill would reduce the deficit by $130 billion over 10 years, Fox News didn't want to talk about that -- it spent far more time highlighting how much the bill would cost instead of how much it would save. And when that didn't seem to work, it tried to discredit the CBO as untrustworthy and unreliable. Never mind that when the CBO issued "favorable" numbers last fall on a Republican health care reform plan, Fox News praised the CBO as "nonpartisan."

The Fox News spin is even confusing its own hosts. Brian Kilmeade can't quite comprehend how a bill can cost money yet reduce the deficit, and Kelly admitted, "I don't understand anything they're talking about when it comes to this potential law."

Fox News' inept war against health care reform, while in keeping with its function as the communications arm of the Republican Party in exile, is making itself look like the Spinal Tap of news. It doesn't really need that "extra push over the cliff" -- after all, that's what it's been speeding toward for years.

At this rate, it probably won't be too long before a Fox anchor spontaneously combusts.

Other stories this week

A whole lot of shaky earthquake claims goin' on at Fox

How much does Fox News oppose health care reform? It's pretending natural disasters didn't happen if they're inconvenient to the anti-reform agenda.

On March 18, Doocy took exception to President Obama's statement that a provision in the health care reform that would help Louisiana cope with Medicaid shortfalls resulting from Hurricane Katrina might also help Hawaii because it "went through an earthquake. "Hold it. What Hawaiian earthquake?" Doocy asked. "There was an earthquake in 1868 that killed 77. There was an earthquake in 1975 that killed two." After noting that the provision applies to states that have suffered a natural disaster "within the last seven fiscal years," Doocy added: "Essentially it boils down to just one state, and that is Louisiana."

Doocy seems to have forgotten that there was an earthquake in Hawaii in 2006. Not only did it cause tens of millions of dollars in damage, the Bush administration "declared a major disaster exists in the State of Hawaii and ordered Federal aid to supplement State and local recovery efforts" as a result of the quake.

But Doocy didn't need to rely on federal agencies for information on the quake -- Fox News reported on it at the time. (Investor's Business Daily similarly ignored its own reporting to suggest there was no recent Hawaii quake.)

It seems that rather than trust the federal government or his own news organization, Doocy chose instead to trust right-wing bloggers, who were spreading the misinformation. That runs counter to a 2007 memo -- issued after Doocy and other Fox hosts falsely claimed that Obama was educated in a madrassa -- in which Fox News vice president John Moody reportedly wrote, "For the record: seeing an item on a website does not mean it is right. Nor does it mean it is ready for air on FNC."

Media Matters has written Fox News requesting that Doocy correct the record. We shouldn't have to, since Fox News is supposed to have a "zero tolerance" policy toward on-air mistakes, but then, these are the same folks that ludicrously insisted that a Fox & Friends graphic in which poll numbers added up to 120 percent contained no errors.

The latest right-wing witch-hunt target: Jim Wallis

Fox News has long been a leader in witch hunts against Obama and his administration (or, really, anyone who can be remotely tagged as liberal). Now Glenn Beck, as an extension of his repeated challenged Beck to a debate over social justice, Beck demurred, his vaguely threatening statements making it clear his witch hunt was more important than reasoned debate: "In my time, I will respond. ... Just know the hammer's coming. ... And when the hammer comes, it's going to be hammering hard and all through the night, over and over."

Right-wing website WorldNetDaily, meanwhile, blundered into the breach with a poorly written article that attempted to put words in Wallis' mouth. WND claimed that Wallis was a "champion of communism," even though Wallis has declared communism to be a "failed" system; asserted that Sojourners has published "a slew of radicals" while ignoring that it has also published a slew of conservatives; and alleged that "Sojourners' official 'statement of faith' urges readers to 'refuse to accept [capitalist] structures and assumptions that normalize poverty and segregate the world by class,' " even though the word "capitalist" -- inserted by WND -- actually appears nowhere in the statement. WND even falsely claimed that Wallis "labeled the U.S. 'the great captor and destroyer of human life.' "

Somehow, we suspect that Beck's upcoming assault on Wallis will be just as divorced from reality as WorldNetDaily's.

Erick Erickson joins the "scumbags" at CNN

Should a blogger who once called a retiring Supreme Court justice a "goat f---ing child molester" be rewarded with a regular commentary gig on CNN? Doesn't matter -- the deal's been done.

CNN announced this week that RedState editor Erick Erickson has joined the network as a political contributor, mainly appearing on John King's new show. The network claimed that Erickson is "a perfect fit" for King's show, adding that "Erick is in touch with the very people John hopes to reach."

Media Matters has detailed Erickson's history of outrageous statements, of which the aforementioned is but one.

Predictably, conservatives defended Erickson's new job, his fellow RedStaters among them. One of Erickson's RedState defenders, however, went a tad off-message: "From Non-Conservatives, to Academics and Liberal Elitists, to self-soiling and unprincipled Professional Politicians and firmly-entrenched good ole boys inside the M(ostly) S(cumbags) M(edia), each of these clowns has a tale of doom about the hell we're headed for compliments of CNN's hand basket."

We have to wonder: Does Erickson consider his new CNN colleagues to be "scumbags"?

This week's media columns

This week's media columns from the Media Matters senior fellows: Eric Boehlert examines the media myth of Obama's "falling poll numbers," and Karl Frisch tells you how to annoy Glenn Beck in five minutes or less.

Facebook, Twitter, YouTube, MySpace, and Digg

Media Matters maintains active online communities on the nation's leading social networking sites. Be sure to join us on Facebook, Twitter, YouTube, MySpace, and Digg and join in on the discussion.

Media Matters Minute now on YouTube

For some time now, radio shows and stations throughout the country have been carrying the Media Matters Minute, a daily, minute-long recap of our work topped off with the "most outrageous comment" of the day. We encourage you to subscribe (YouTube / iTunes /RSS) to the Minute's daily podcast, hosted by Media Matters' Ben Fishel.

This weekly wrap-up was compiled and edited by Terry Krepel, a senior web editor at Media Matters for America.

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The world's best small music venues

Guardian Unlimited

- 1 days and 23 hours ago

Musicians, DJs and authors to reveal their favourite hangouts

Have your say on the Travel blog

HiFi, New York

HiFi is the best rock'n'roll bar in NYC.The room is covered with empty album sleeves and the juke box is hands-down the best in the city â€“ I believe there are about 3,000 albums on it, so you can't complain about them not having your song. There is a fantastically affordable happy hour and a great local crowd. Like the rest of the East Village, it can get a bit much on weekend nights, but most of the time it's my favourite bar in town.
· 169 Avenue A, +1 212 420 8392.
Craig Finn, lead singer of the Hold Steady

Pegu Club, New York

The entrance to the Pegu is an unassuming doorway on the south side of West Houston Street. It's only when you are up the stairs that the glory of this place hits you. It is like going back to the great clubs of the 20s, when the staff were pretty and jazz and cocktails ruled. On a recent visit, two amazing Django Reinhardt-style guitarists were swinging through 30s classics. Cocktails are taken seriously here â€“ the art of proper, classy drinking is almost a motto. At the weekend it can get pretty busy as it is becoming the "in" place.
· 77 West Houston Street, +1 212 473 7348.
James Pearson, artistic director, Ronnie Scott's, London

Po' Monkey's, Mississippi

It was a balmy night in September when I visited Po' Monkey's juke joint. It's a ramshackle hut powered by a single cable in the tiny town of Merigold, deep in the Mississippi delta. A poster on the door warned: "Bring your liquor inside but not your beer." The walls were cluttered with posters and age-old postcards, while toy monkeys swung from the rafters. It was low lit â€“ smoky but inviting, with beer and whiskey flowing freely. Terry "Harmonica" Bean took to the tiny stage, elbow to elbow with the crowd, and delivered a mind-blowing, foot-stamping performance that will stay with me forever. Delicately soulful cries came from his ageing gruff voice, while stupendous bluegrass melodies oozed effortlessly from his antique steel guitar. This was raw blues at its authentic and spine-shivering best.
· +1 662 514 7488, 15km from Cleveland.
Dan Hipgrave, co-founder of Original Music Company (originalmusictravel.com), which launched this month and specialises in music-themed holidays

The Spirit Store, Ireland

The Spirit Store in Dundalk, County Louth, is on the edge of town beside a small harbour. There's a small, friendly bar downstairs which opens around 4pm, but it is the live music upstairs that is the main draw. You would be hard-pressed to find anywhere as welcoming to an artist and more genuinely music-driven in its programming of events. That's why I keep going back there to play, and why many other artists who have outgrown the 120- or so capacity venue keep returning. So many venues and promoters are about the money but Derek Turner, who books the music, is driven by something much more.
· +353 42 9352697.
Duke Special, musician. His DVD box set, The Stage, A Book & the Silver Screen is out now

The Hideout, London

Not exactly a venue, not exactly a bar, entrance to Trishas/The Hideout/that door on Greek St (as it is variously known), is obtained by boldly knocking on what appears to be the entrance to a flat above a shop, striding through a starkly lit corridor and down a flight of stairs, before mumbling an explanation to the owner as to why you don't appear to be in possession of a membership card â€“ having accidentally put it through the washing machine normally does the trick. Inside, you'll find a cupboard-sized, candle-lit cavern which can be hired out for private music showcases. But stumble in unannounced after hours on a weekend and you might also find a doo wop or jazz band sandwiched into the corner between the usual crowd of transvestites, metropolitan hipsters and veteran Italian locals.
57 Greek Street, Soho, London.
Krissi Murison, editor, NME

The Shed North Yorkshire

I first played at this blink-and-you'll-miss-it shed in the tiny village of Brawby back in 1998. It only held 64 people and we scraped our legs on the front row's knees. It has since moved to Hovingham village hall, though it retains its name. The man behind The Shed, Simon Thackray, has presented events from the Fish and Chip Van Tour with a trombonist, to mixed media knitting installations â€“ saxophonist Lol Coxhill playing free jazz in a skip to coach trips for folks in knitted Elvis wigs touring sites of Elvisian interest in Ryedale. My own band, Hank Wangford and the Lost Cowboys, started a tradition of Christmas gigs at The Shed, where we play morose songs and have a riotously miserable time. The Shed was the inspiration for my village hall tour around Britain, which I am currently writing up as a book. And, after 235 villages, The Shed is still the loony best.
· 01653 668494.
Hank Wangford, writer and musician. His CD, Whistling in the Dark, is out now

A38, Budapest

For me, the greatest gig of 2009 was at A38, a huge old ship that used to lug coal up and down the Danube. The lower deck is now a state-of-the-art live music venue, but bits of engine room equipment are still there. Even though the boat is held down in dry dock by 100 tonnes of concrete, the bottles still jingle on the shelves of the bar when the parties get wild. The booking policy is great â€“ they've had cutting-edge electronic artists such as Ikonika, Dorian Concept and Foreign Beggars play recently. And nothing compares with the signature dish of the restaurant on the upper deck: rooster stew, complete with the crest and testicles of the bird.
· +36 1 464 39 40.
Mary Anne Hobbs, Radio 1 DJ. Her show is broadcast on Thursdays 2-4am

Wild At Heart, Berlin

Wild At Heart is a whisky-soaked, no-nonsense rock'n'roll joint in Berlin's old anarchist district, Kreuzberg: a seven-nights-a-week venue painted blood red, crammed with Elvis memorabilia, Hawaiian gods and a lifetime's supply of hard liquor. For 15 years it has presented bands from all over the world â€“ mostly punk, rockabilly, psychobilly, 60s garage and surf. I spent a memorable evening there talking to TV Smith from the Adverts and another with Wreckless Eric, both of whom started out with punk label Stiff Records in 1977, and I've played there with my band, the Flaming Stars. The music's loud, but the welcome is friendly, and the club also runs the Tiki Heart cafe and clothes shop next door, where you can eat, drink and kit yourself out in a spectacular variety of rock'n'roll clobber.
· Wienerstrasse 20, +49 30 610 747 01.
Max Décharné, singer in the Flaming Stars and author of A Rocket in My Pocket: The Hipster's Guide to Rockabilly, to be published by Serpent's Tail in June

Mesa de Frades, Lisbon

Mesa de Frades in Alfama, the oldest district of Lisbon, is the sort of place you dream of hearing fado, the traditional soulful Portuguese music. A tiny converted chapel with tiled walls, it is full of locals and quality performers booked by owner Pedro Castro, a great guitar player. You can come for the music, which starts late â€“ around 11pm â€“ or book a table and come for an excellent dinner beforehand. A couple of years ago I sat here watching Carminho, the amazing young fado singer who is now the talk of Lisbon. When the music starts, the doors are shut to enclose the tiny performing space. It's what fado in Lisbon should be, but so rarely is.
· Rua dos Remedios 139A, +351 91 702 9436, mesadefrades.com. Booking is essential.
Simon Broughton, editor of Songlines magazine (songlines.co.uk/musictravel)

Il Folk Club, Turin

In the heart of Turin, off Piazza Statuto, you'll find the best of all worlds: from Wednesday to Saturday Il Folk Club plays host to Italian and international jazz, folk and world musicians. How this Italian institution â€“ legendary in Turin for over 20 years â€“ has remained generally unknown to travellers and music junkies outside Italy is a mystery. Alongside its regular programme, Il Folk Club is also the launching point for Radio Londra, a monthly mini-festival which fuses British musicians such as Jim Mullen, Kit Downes, Brandon Allen and Quentin Collins Quartet, with local stars such as Mario Pozza, Enzo Zirilli and Dado Moroni. The bar is simple â€“ one central room with space for about 150 people, exposed brick walls, and a stage â€“ so the focus is always on the incredible music.
Via Ettore Perrone 3, Turin.
Sam Sollai, buyer and events coordinator, Ray's Jazz at Foyles

Gerbard, Barcelona

This little neighbourhood bar used to have a green door with panes that rattled when you opened it, but it has now been replaced with something more solid, partly to keep the sound in. It's run by Mar and Nacho, both dyed-in-the-wool culés (Barcelona supporters), and nights there are long and loud. You can hear Sam Lardner, an American resident who plays his own fusion of flamenco and bossa nova, or wonderful classical and flamenco guitarists like Daniel Figueras and Pedro Javier Hermosilla, or the Covers Project, with frontman Philip Stanton. The eating and drinking are delicious too â€“ Galician-style octopus, traditional meatballs, pimientos de padron (small green peppers), and wine for not much more than a euro a glass. A great night out in the Alta Zona.
· C/ Ivorra 24, Sarria, Barcelona, +93 203 4988.
Rupert Thomson, author living in Barcelona. His latest book, This Party's Got to Stop, will be published on 8 April

La Casona del Molino, Salta, Argentina

Salta, in north-west Argentina, is well-known for its folk music heritage. This has given rise to the creation of pena, which roughly translates as a place where musicians and music lovers come together. Seven nights a week you can experience this at La Casona. The venue's five colonial rooms are filled to the brim with musicians, professional and amateur, folk, jazz and others, locals who come down from the Andes bearing pan pipes and drums, and some foreign visitors, all coming together to jam the local tunes. As a musician, I found great comfort in the fact that this kind of place exists in the world. And of course, many people come simply for the music.
· La Casona del Molino, Caseros.
Lizzie Ball, violinist and singer. She will be performing â€“ and launching her album â€“ with Machaca at La Linea Festival in the Purcell Room on London's South Bank on 27 April

Salón Rosado de la Tropical, Havana

The first time I asked a taxi driver to take me to Havana's Salón Rosado de la Tropical back in 1989 he said it was a place for Cubans, not foreign tourists â€“ and certainly not lone women â€“ and I'd better watch out as it could be rough. He'd obviously never been inside this mecca of Cuban dance music, where all the top bands play regularly, testing their latest material in front of the sexiest dancers on the island. In Cuba, most music venues are geared to tourists and too expensive for ordinary Cubans, who are often not allowed in anyway. Not so the Salón Rosado. This is the closest you can get to hanging out with a Cuban clientele. Dedicated to the memory of Beny Moré, Cuba's touchstone band leader of the 1950s, it started out life a Spanish cultural centre at the beginning of the 20th century. These days there's a balcony reserved for tourists overlooking the dance floor where, if you're lucky, you may rub shoulders with the musicians as they gather for the gig. Although today reggaeton and hip-hop dominate street tastes, Salon Rosado continues to offer a window on to the latest music scene and is a dancer's dream.
· Avenida 41 esq. 46, Nicanor del Campo, Marianao, +53 7 203 5322.
Jan Fairley has been travelling to Cuba since 1978 and is writing a book on women and music in Cuba

Liquid Room, Tokyo

Leading Japanese venue Liquid Room has been going for about 15 years and hosts weekly bands and DJs from Japan and around the world. The website may say it closes at 12, but the last time I played there, as The Orb, they didn't let us out till 6am. There's a beautiful cafe upstairs and the friendly enthusiasm of Tokyo clubbers has to be experienced to be believed. The last time I played there I took a bag of Space Dust (the sweet!) which made me very popular.
· Higashi, Shibuya-ku, Tokyo, +81 3 5464 0800, liquidroom.net.
Alex Paterson, co-founder of The Orb and HFB, his new project. HFB's first three EPs are available from 12 April on Malicious Damage Records

New Africa Shrine, Lagos, Nigeria

Lagos is not your classic tourist destination; it's a prohibitively expensive city of 14 million people and a crime record to frighten even the toughest traveller. But Nigeria's notorious capital does have one musical landmark worth going the extra mile for: the New Africa Shrine. It's named after the legendary club run by the late musical activist Fela Kuti, which was razed by soldiers. Fela's daughter Yeni and her musician brother Femi have built up a nightclub that can hold thousands and has live music throughout the week. It's not for the faint-hearted, but the Shrine is probably the safest place in Lagos: it has its own police force. You'll get a warm welcome, and hear some of the best live music in the region.
· Pepple Street, Ikeja.
Rose Skelton, music and travel journalist specialising in West Africa

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