Publication Date: 2010 Mar 12 PMID: 20225075Authors: Saleem, A. B. - Chadderton, P. - Apergis-Schoute, J. - Harris, K. D. - Schultz, S. R.Journal: J Comput NeurosciDuring anesthesia, slow-wave sleep and quiet wakefulness, neuronal membrane potentials collectively switch between de- and hyperpolarized levels, the cortical UP and DOWN states. Previous studies have shown that these cortical UP/DOWN states affect the excitability of individual neurons in response to sensory stimuli, indicating that a significant amount of the trial-to-trial variability in neuronal responses can be attributed to ongoing fluctuations in network activity. However, as intracellular recordings are frequently not available, it is important to be able to estimate their occurrence purely from extracellular data. Here, we combine in vivo whole cell recordings from single neurons with multi-site extracellular microelectrode recordings, to quantify the performance of various approaches to predicting UP/DOWN states from the deep-layer local field potential (LFP). We find that UP/DOWN states in deep cortical layers of rat primary auditory cortex (A1) are predictable from the phase of LFP at low frequencies (< 4 Hz), and that the likelihood of a given state varies sinusoidally with the phase of LFP at these frequencies. We introduce a novel method of detecting cortical state by combining information concerning the phase of the LFP and ongoing multi-unit activity.post to: CiteULike

Publication Date: 2010 Mar 11 PMID: 20222969Authors: Garg, A. - Tewari, R. - Raghava, G. P.Journal: BMC BioinformaticsABSTRACT: BACKGROUND: Identification of novel drug targets and their inhibitors is a major challenge in the field of drug designing and development. Diaminopimelic acid (DAP) pathway is a unique lysine biosynthetic pathway present in bacteria, however absent in mammals. This pathway is vital for bacteria due to its critical role in cell wall biosynthesis. One of the essential enzymes of this pathway is dihydrodipicolinate synthase (DHDPS), considered to be crucial for the bacterial survival. In view of its importance, the development and prediction of potent inhibitors against DHDPS may be valuable to design effective drugs against bacteria, in general. RESULTS: This paper describes a methodology for predicting novel/potent inhibitors against DHDPS. Here, quantitative structure activity relationship (QSAR) models were trained and tested on experimentally verified 23 enzyme's inhibitors having inhibitory value (Ki) in the range of 0.005-22(mM). These inhibitors were docked at the active site of DHDPS (1YXD) using AutoDock software, which resulted in 11 energy-based descriptors. For QSAR modeling, Multiple Linear Regression (MLR) model was engendered using best four energy-based descriptors yielding correlation values R/q2 of 0.82/0.67 and MAE of 2.43. Additionally, Support Vector Machine (SVM) based model was developed with three crucial descriptors selected using F-stepping remove-one approach, which enhanced the performance by attaining R/q2 values of 0.93/0.80 and MAE of 1.89. To validate the performance of QSAR models, external cross-validation procedure was adopted which accomplished high training/testing correlation values (q2/r2) in the range of 0.78-0.83/0.93-0.95. CONCLUSIONS: Our results suggests that ligand-receptor binding interactions for DHDPS employing QSAR modeling seems to be a promising approach for prediction of antibacterial agents. To serve the experimentalist to develop novel/potent inhibitors, a webserver "KiDoQ" has been developed (http://crdd.osdd.net/raghava/kidoq), which allows the prediction of Ki value of a new ligand molecule against DHDPS.post to: CiteULike

Publication Date: 2010 Mar 11 PMID: 20223836Authors: Xiao, S. J. - Zhang, C. - Ji, Z. L.Journal: BioinformaticsSUMMARY: The tissue-specific genes are a group of genes whose function and expression are preferred in one or several tissues/cell types. Identification of these genes helps better understanding of tissue-gene relationship, etiology and discovery of novel tissue-specific drug targets. In this study, a statistical method is introduced to detect tissue specific genes from more than 123125 gene expression profiles over 107 human tissues, 67 mouse tissues and 30 rat tissues. As a result, a novel subject-specialized repository, namely the Tissue-Specific Genes Database (TiSGeD), is developed to represent the analyzed results. Auxiliary information of tissue-specific genes were also collected from biomedical literatures. AVAILABILITY: http://bioinf.xmu.edu.cn/databases/TISGED/index.html. CONTACT: appo@bioinf.xmu.edu.cn or zhiliang.ji@gmail.com.post to: CiteULike

Publication Date: 2010 Mar 11 PMID: 20223835Authors: Narang, V. - Mittal, A. - Sung, W. K.Journal: BioinformaticsMOTIVATION: Discovery of nucleotide motifs that are localized with respect to a certain biological landmark is important in several applications, such as in regulatory sequences flanking the transcription start site, in the neighborhood of known transcription factor binding sites, and in transcription factor binding regions discovered by massively parallel sequencing (ChIP-Seq). RESULTS: We report an algorithm called LocalMotif to discover such localized motifs. The algorithm is based on a novel scoring function, called spatial confinement score, which can determine the exact interval of localization of a motif. This score is combined with other existing scoring measures including over-representation and relative entropy to determine the overall prominence of the motif. The approach successfully discovers biologically relevant motifs and their intervals of localization in scenarios where the motifs cannot be discovered by general motif finding tools. It is especially useful for discovering multiple co-localized motifs in a set of regulatory sequences, such as those identified by ChIP-Seq. Availability and Implementation: The LocalMotif software is available at http://www.comp.nus.edu.sg/~bioinfo/LocalMotif CONTACT: ksung@comp.nus.edu.sg SUPPLEMENTARY INFORMATION: Supplementary description of the method, algorithm and results is available at Bioinformatics online.post to: CiteULike

Publication Date: 2010 Mar PMID: 19955235Authors: Herai, R. H. - Yamagishi, M. E.Journal: Brief BioinformTrans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, 'Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence?', we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation.post to: CiteULike

We all have film sequences that stick in our minds. Some are shared by many – such as the shower scene from Psycho – others are particular to us. Here our film critic and a panel of leading movie-makers reveal their favourites. What are yours?

Who will ever forget the first time they saw the 45-second shower-room murder in Hitchcock's Psycho? I remember 1959 and 1961 as the years when my first two children were born. But the first thing that comes to mind about the year in between was seeing Psycho, which I'd been looking forward to since a radio programme I'd produced the previous October, when Hitchcock had enticingly described Psycho as "my first real horror film". Entering the Plaza, Lower Regent Street, the day the film opened, I passed the cardboard cut-out of Hitchcock in the foyer, from which a tape recording of the Master's familiar Leytonstone undertaker's voice warned us what would happen if we gave away the ending.

Half an hour into the movie, when Janet Leigh stared out at us from the floor, a man sitting in front of me staggered into the aisle and vomited: testimony to the sensitive stomachs of the time, or (as several other people I know witnessed a similar incident at the Plaza that week) evidence that Paramount's publicity department had hired a method actor for the film's opening run?

Such indelibly iconic moments have been part of moviegoing since the Lumière brothers' first public screening of a dozen short scenes in December 1895. One of them had the audience recoiling from a train entering a station, another had them chuckling when a cheeky boy tricked a gardener into spraying himself with a hosepipe. People judge a movie by the strength of its story and overall impact, but ultimately what they remember are individual moments and sequences. This perhaps reflects the very nature of film, which is a rapid succession of still pictures that provide an illusion of motion. And until the coming of cassettes and DVDs, few of us were able to see a picture over and over again or re-view a sequence. So we had to replay it in our minds, and naturally we'd often get it wrong. Which is how "Play it again, Sam" entered the language instead of: "Play it, Sam, play 'As Time Goes By'."

James Stewart seems to have been thinking of this approach to cinema when he talked to Peter Bogdanovich about his craft: "What you're doing is... you're giving people little... little, tiny pieces of time... that they never forget." This is echoed by Walker Percy in his 1961 novel The Moviegoer. Some people, his narrator says, "treasure memorable moments in their lives: the time one climbed the Parthenon at sunrise", but "what I remember is the time John Wayne killed three men with a carbine as he was falling to the dusty street in Stagecoach, and the time the kitten found Orson Welles in the doorway in The Third Man". Likewise Jean-Dominique Bauby, the paralysed French writer, describes in The Diving Bell and the Butterfly how he'd lie in the hospital recreating favourite scenes from Touch of Evil, Stagecoach, Moonfleet and Pierrot le fou. Canny film-makers have cottoned on to the idea, like James Cameron, who says: "You try to create one or more emotional, epiphanous moments within a film."

These moments come in many forms – simple, complex, lyrical, violent, gentle, witty, romantic, revelatory – and, if they stick, become as real as any other memory. They can range from the split-second close-up of the suave spy's missing half-finger in Hitchcock's The 39 Steps to the protracted pursuit of Cary Grant by the crop-dusting plane in North by Northwest, from the in-your-face eye-slicing in Buñuel's first silent movie, the avant-garde Un Chien Andalou, to the puzzling sequence of the Chinese businessman's mysterious box in the same director's mainstream success Belle de Jour 40 years later. Like your favourite jokes, your cherished movie moments reveal something about you and, if shared, they can be the beginning of a beautiful friendship, especially if one of them is the final sequence in Casablanca that features that line.

My own favourites? The Odessa Steps sequence from Battleship Potemkin. The love at first sight between John Wayne and Maureen O'Hara in The Quiet Man, the lust at first sight between Fred McMurray and Barbara Stanwyck in Double Indemnity. The children running through the woods to see a train in Pather Panchali and finding grandmother dead on the way back. The cruelly comic soccer match in Loach's Kes. Donald Sutherland and Julie Christie making love in a Venetian hotel in Don't Look Now. The slow-motion mayhem let loose in The Wild Bunch after William Holden says: "If they move, kill 'em!" Perhaps my single favourite moment comes in Citizen Kane, where Kane's now elderly friend Bernstein tells the reporter about an epiphanic memory of seeing a girl in a white dress on the New Jersey ferry in 1896. "I'll bet a month hasn't gone by since that I haven't thought of that girl." It's a moment about remembering a moment, and the actor Everett Sloane makes it so vivid we think we've seen that girl ourselves.

THE FRENCH CONNECTION (1971) - THE SUBWAY CHASE

Chosen by Ryan Fleck, the American indie film director, writer, editor and cinematographer, best known for co-writing and co-directing with partner Anna Boden Half Nelson and Sugar correct(out now on DVD).

The villain's on the elevated subway. You think he's going to get away because a person on foot can't keep up with the subway... But Gene Hackman jumps in a car and starts chasing the subway, riding underneath it, going at 80mph, swerving in and out of traffic. I first saw this scene on video when I was 18 or 19, in college. I loved it.

In action scenes nowadays you can chalk everything up to some kind of computer effect. Audiences no longer really believe that what they're seeing exists anymore. When The French Connection was made that notion didn't really occur to people. What you saw was usually really happening in front of the lens. It was raw. I did a little bit of research about how they shot the scene. Phenomenal. Basically they just did it. There was no security blocking off other traffic, just Hackman in a car with a camera mounted on the front. They went crazy, lost their minds, and went for it.

It was the kind of thing that you just would never get away with these days. I'm editing a movie right now that has a teenager walking on the Brooklyn Bridge, considering suicide. He steps out on to a ledge, over traffic... It never even occurred to put the actual kid out on the ledge, on a bridge, over traffic because we knew there was no way authorities would let us do that. So there's camera trickery. Back in the 70s we'd have just thrown a child out over the ledge, seen what happened, and shot it.

JULES ET JIM (1962) - THE BICYCLE SCENE

Chosen by Ken Loach, writer/director of the influential docudrama Cathy Come Home, and director of nearly 30 films including Kes, Riff-Raff, My Name is Joe and Looking for Eric. He won the 2006 Palme d'Or at Cannes for The Wind that Shakes the Barley.

This scene always cheers you up. Jeanne Moreau and the two guys on their bicycles in the sun in France, the music that goes with it... Partly it evokes what you imagine to be the perfect French vacation but also it's a very fine bit of film-making.

When you're in the business and have been in the business a long time, you tend to dismember about 99% of films as you're watching. The time when you used to watch a film just for enjoyment is difficult to recapture. But just occasionally a film will transcend that. The sense of enjoyment with this trio on their bicycles is perennial. It's completely evocative of that carefree young moment, the age when people are carefree. And then of course, for these three, it will all be ruined by the war.

The song that was composed for the film – "Le tourbillon" – became very famous. I'd sing it for you if I wasn't surrounded by colleagues who would take the piss. I think film music that tells you what to think is cheap – the film should do that without that prompting. But in Jules et Jim it is music in relation to the images, the music has an independent existence and there's a relationship between the two.

It is not something subterranean, there to steer you through every second and push you into feelings that the pictures don't generate themselves.

ALL ABOUT EVE (1950) - BILL'S BIRTHDAY PARTY

Chosen by Beeban Kidron, who came to international attention directing the BBC's adaptation of Jeanette Winterson's novel Oranges Are Not the Only Fruit in 1990. She has since directed several feature films including Bridget Jones: The Edge of Reason and To Wong Foo, Thanks for Everything, Julie Newmar.

Every single line in this scene is quotable. It's the most beautifully written thing, from an era of cinema very closely knitted to the theatre, when the words were supposed to evoke things rather than just be things for people to say while the pictures were going on. That's something that's very often lost 60 years later.

Margo, played by Bette Davis, is a great Broadway actress at the pinnacle of her power: brilliant, sophisticated, bitchy. Her assistant Eve, meanwhile, played by Anne Baxter, is simpering, beautiful and very, very ambitious. Eve is trying to replace Margo, trying to get her next part on Broadway and take her lover, Bill. This is the scene where Margo finally loses her rag, having waited upstairs for Bill to throw him a party before discovering that he's been downstairs with Eve for 20 minutes.

The scene sums up the central themes of the film, to do with Margo's insecurity about age and about the way that Eve is eating into her life. This is referred to in the dialogue all the time: Margo finds Eve and Bill talking and immediately asks if she can join in – "Or isn't it a story for grown-ups?" Bette Davis, despite being so powerful, gives a phenomenal performance of insecurity. That is very, very rarely drawn in the cinema.

The question of ageing and of being replaced by the younger, more beautiful woman is something we can still understand today.

JASON & THE ARGONAUTS (1963) - THE SKELETONS SCENE

Chosen by Nick Park, Oscar-winning animator and writer/director of the Wallace and Gromit films.

As a boy I was into monsters, heroes going off on adventures – and stop-motion animation. I saw trailers for this film and it seemed to be everything I wanted. I remember being at a school fair, just before Christmas, and being desperate to get home to watch it.

The scene that stood out the most, that I found both horrifying and enthralling, was the skeleton fight at the end. The heroes are all live action and the monsters are all done with stop-frame animation. It was a terrific technical feat – I think there were eight animated skeletons or more, cut together quite seamlessly with the live action. The whole choreography of it was amazing. But the story, too, really caught my imagination. These skeletons were planted like seeds, by a wizard chap spreading dragons teeth, and then dead soldiers grow up to fight the Argonauts. So exciting.

At around the same time I saw Ray Harryhausen, the animator, explain on television how he had done the skeletons. I immediately went and built my own models with wire and foam – I think I was planning to film something with my friends, live action, cut together with a sea monster made out of a coat hanger and nylon tights.

Disney films didn't make me want to go home and do it myself because it was shrouded in mystery and technique. But when I saw the skeletons in Harryhausen's film I wanted immediately to do it myself, because you got a sense of how it might be done.

2001: A SPACE ODYSSEY (1968) - THE FINAL SCENE

Chosen by Stephen Poliakoff. After starting out as a playwright, Poliakoff turned to writing and directing television dramas including Shooting the Past, Perfect Strangers and the award-winning The Lost Prince. His feature films include Hidden City and most recently Glorious 39.

Still, after 40 years, people are arguing about the ending of 2001: A Space Odyssey. What the ending means to the film. The computer taking over, the menacing computer howl, the foetus – it has passed into cinema folklore. Science fiction was not a genre that attracted me much, and it was very unsexy in the 1960s. But Kubrick's film was the most original I had ever seen. It came at me for the first time, completely alone, in a cinema on a summer afternoon in 1968. I was 15, and it made an extraordinary impression on me. There was a lot more mainstream "auteur cinema" than there is now, Hollywood studios producing personal films. Nevertheless Kubrick stood alone, a titanic figure that obsessively made films, under great secrecy, and with nobody interfering.

I had never seen such a bold use of cinema, and certainly never such an incredibly obscure ending. To have spent all that time and money and to have the daring – some would say foolhardy daring, but nevertheless a magnificent daring – to end the film on such an elusive and obscure note, I found it amazing as a 15-year-old that anybody should have the balls to do that. It excited me and changed my whole view of what you could do as a writer, whatever medium you were attempting – Kubrick's aspiration to be original. Now it's been much imitated but 2001 was extraordinarily ahead of its time, and has continued to survive and influence generations.

TAXI DRIVER (1976) - THE MIRROR SCENE

Chosen by Stephen Woolley, the award-winning producer best known for his collaborations with director Neil Jordan including Interview with the Vampire and The Crying Game. Recent projects include How To Lose Friends and Alienate People and the forthcoming Made in Dagenham. In 2005 he made his directorial debut with Stoned.

I remember seeing Taxi Driver for the first time in Paris in the 70s. The taxi gliding across New York's wet streets, smoke coming out of the subways, it was all incredibly delicious. It had this thundery Bernard Herrmann score, and when Robert De Niro did his "are you talking to me?" sequence in front of the mirror you suddenly sensed the degree of anger there. It was all bottled up until he explodes with this bravura performance. It's very clever, very economical, everything concentrated on his eyes.

Sequences like this are not only successful because they are so beautifully created but also because they often come at a point in a film where you begin to realise where it's going, you think, "oh my god, I know what this is about". Here you become aware that not only is Travis Bickle schizophrenic but he's aware of his own schizophrenia. He's like a genie in a bottle and you're waiting for him to let the genie out – which he does brilliantly in that horrific sequence later on where he shoots Harvey Keitel's character and saves Jodie Foster's.

The scene was improvised but De Niro had tried out a version of it in an earlier film he made with Brian De Palma, I think it's called Hi Mom! I didn't see it until years after watching Taxi Driver and I remember thinking "I can't believe it – the thing he does in Taxi Driver!"

CARRIE (1976) - THE BLOOD AT THE PROM SCENE

Chosen by Edgar Wright, who co-created Channel 4's Spaced, and has collaborated with comedian Simon Pegg on hit films Shaun of the Dead and Hot Fuzz. His latest directing project, Scott Pilgrim vs the World, is out later this year.

I always describe Carrie as the Grease of horror movies: it resonates with all ages because everybody remembers their awkward teenage phase and can watch it and say – I was the bully or the victim or the person who did nothing. It explores how apocalyptic your rage can be as a teenager. Carrie's not a killer, she's a girl who has been bullied and through a terrible confluence of events ends up burning the school down.

It's also unusual for a horror film. It doesn't have someone being killed every 20 minutes and then a climax – it builds to one huge climax at the prom. School bullies have fixed the prom so that Carrie White will win and they can humiliate her by tipping a bucket of pig's blood over her in front of the whole school. The scene and the excruciating build-up to it is one of the greatest set pieces of all time, full of suspense, with a monumental payoff.

A crane shot sets up the sequence so you know where everyone is positioned and that the bucket of blood is above Carrie and Tommy's heads. Once the plot is set in motion Pino Donaggio's score takes over. The resulting sequence is pure opera.

I first saw Carrie on VHS with my brother's friend when I was about 12. I obsessively read about horror movies and was dying to see it. I've watched it so many times since. De Palma planned the sequence for months and battled the studio over the time spent on filming it. But it was worth the blood, sweat and tears. It still leaves audiences speechless.

REAR WINDOW (1954) - THE OPENING SCENE

Chosen by Claire Denis, who made her directorial debut in 1988 with Chocolat. Subsequent films include Good Work and 35 Shots of Rum. Her latest, White Material, is out in the summer.

We don't have courtyards in France like they do in New York, where Hitchcock's film is set, but we have street buildings that are set very close to each other. From where I stand in my kitchen or my bedroom I can watch neighbours' windows very easily. I'm intrigued by voyeurism, about what is behind windows, and often in my films I stage a scene as if I was peeping in from outside.

The situation Hitchcock establishes in the opening scene of Rear Window is the ultimate voyeuristic situation. The character played by James Stewart has broken his leg, has nothing to do but linger behind his window and watch. He is passive but eager to find something – to be a witness of something, or to give his imagination something to chew on. As a spectator in a cinema theatre, you are a sort of prisoner in a chair, like he is.

• Alfred Hitchcock
• Bette Davis
• Stanley Kubrick
• Martin Scorsese
• Robert De Niro

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

[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 turn-based aerial dogfight game, a puzzle platformer by Karoshi creator Jesse Venbrux, an interactive fiction game about the Russian Roulette, a visual novel, and a game about gardening that doesn't feature zombies in it.

Here's the highlights from the last seven days:

Game Pick: 'Steambirds' (Andy Moore and Dan Cook, browser)
"Steambirds is a turn-based aerial dogfight game that is viewed from a top-down perspective, where players are given command of a squadron of planes with their own unique abilities to deploy. Fans of strategy games like the Advance Wars series would feel right at home here, with the only differences being that combat takes place in the skies and rigid tile-based movement has been done away with."

Game Pick: 'Redder' (dessgeega, browser)
"In Redder you play as an astronaut forced to make an emergency landing on an alien planet after finding out that she has run out of crystals to power her ship. This 2D platformer features a world map, regular checkpoint locations, and an unlimited number of retries to assist players who are unaccustomed to difficult challenges."

Game Pick: 'Maru' (Jesse Venbrux, freeware)
"Maru is a simple platformer that plays rather similarly to Jesse's other creation called Frozzd, although the tone in both games are practically on different ends of a spectrum. The adventure basically involves leaping from one planet to another to collect the spirits or souls of other creatures that look just like the protagonist, then figuring out how to get to the portal that will transport you to the next area and continue with your mission."

Game Pick: 'Six-Chamber Champion' (C.E.J. Pacian, freeware)
"Six-Chamber Champion is a single-room IF game created by C.E.J. Pacian in under two hours for a 371-in-1 Klik & Play Pirate Kart event held last weekend. This particular adventure should be tried out without reading anything about it at all, since every screenshot and mention of it only serves to spoil the best bits. Suffice to say that the story involves a gun and trying to avoid killing yourself."

Game Pick: 'Air Pressure' (Bento Smile, freeware)
"Bento Smile's Air Pressure is a visual novel with original graphics and music, featuring quite a number of branching story paths but only three endings to discover. The entire adventure takes about ten minutes to play through, and Terry Cavanagh (developer of VVVVVV) even liked it enough to recommend the game to everyone."

Game Pick: 'Extreme Gardening' (Jan Willem Nijman, freeware)
"Extreme Gardening is a short puzzle game about trimming hedges. On each of the fifteen levels, players are shown how the hedge should look, then given 10 seconds to cut it into shape using the mouse to click and drag the hedge away."

Like many in the insulated west, I've long been fascinated by North Korea, what life is like in there, and what will happen to the peninsula after the walls come down. (Of course, I'm half a world away, so I have the luxury of being fascinated with North Korea. Life inside the country, I suspect, is beyond rough and might get even worse in the first years of inevitable reunification.) I've read extensively on the country, enough so that I almost understand the concept of juche. And I've explored the country a bit in my fiction. My novel-in-progress has a sequence in which an over-the-hill rocker is invited to perform a goodwill concert in Pyongyang, although I'm not sure the subplot it's part of will earn space in the final draft. My hometown website boston.com (disclosure: I used to consult for 'em) has a terrific feature called The Big Picture that tells news stories in photographs. A year and change ago, the section ran a gripping Recent scenes from North Korea, a collection of 32 photos, all taken in 2008, some from wire services, some from freelancer Eric Lafforgue's then-recent trip, some shot inside the nation, some shot across the border. And now you can see On the Spot with Kim Jong-il, 31 photos from North Korea's state-run "news" agency, showing Dear Leader, usually in a parka, inspecting various industrial facilities. It's an astonishing series of portraits of a man and a culture disconnected from reality, surveying an empire that does not exist....

Language and Cognitive Processes, Vol. 23, No. 5. (2008), pp. 749-766.

Two experiments investigated 4-year-olds' use of descriptive sentences to learn non-obvious properties of unfamiliar kinds. Novel creatures were described using generic or nongeneric sentences (e.g., <i>These are pagons.</i> <u><i>Pagons</i></u><i>/</i><u><i>These pagons</i></u> <i>are friendly</i>). Children's willingness to extend the described property to a new category member was then measured. The results of Experiment 1 demonstrated that children reliably extended the property to new instances after hearing generic but not nongeneric sentences. Further, the influence of generic language was much greater than effects related to the amount of tangible evidence provided (the number of creatures bearing the critical property). Experiment 2 revealed that children continued to extend properties mentioned in generic descriptions even when incompatible evidence was presented (e.g., an example of an unfriendly pagon). The findings underscore preschoolers' keen understanding of the semantics of generic sentences and suggest that inferences based on generics are more robust than those based on observationally grounded evidence.
Craig Chambers, Susan Graham, Juanita Turner

Are you still looking for the best image editor on the Web? If that is the case, I am not exactly sure if this particular site would compete for that accolade, but the fact remains that it is surely practical.

Using it involves little more than uploading your image and then choosing one from the many effects that are available on the main page. There are not only a lot of them, but I must also add that some of them are really novel (and funny).

Read more

Learn more about PicFast.com in Dataopedia.com

Find out how much PicFast.com is worth with Stimator.com

Kate from Aussiecon, the upcoming World Science Fiction convention in Melbourne, sez, "The deadline for sending in your Hugo Awards nomination ballot is fast approaching! The Hugo Awards are awards for excellence in the field of science fiction and fantasy. The nomination deadline is Saturday, March 13, 2010 23:59 PST. To submit a ballot you must either be a member of Anticipation, the 2009 Worldcon, or have registered for Aussiecon 4, the 2010 Worldcon, by January 31st." For the record, my novel Makers is eligible for nomination....

Publication Date: 2010 Mar 10 PMID: 20220021Authors: Ozkaynak, E. - Abello, G. - Jaegle, M. - van Berge, L. - Hamer, D. - Kegel, L. - Driegen, S. - Sagane, K. - Bermingham, J. R. Jr - Meijer, D.Journal: J NeurosciThe segregation and myelination of axons in the developing PNS, results from a complex series of cellular and molecular interactions between Schwann cells and axons. Previously we identified the Lgi4 gene (leucine-rich glioma-inactivated4) as an important regulator of myelination in the PNS, and its dysfunction results in arthrogryposis as observed in claw paw mice. Lgi4 is a secreted protein and a member of a small family of proteins that are predominantly expressed in the nervous system. Their mechanism of action is unknown but may involve binding to members of the Adam (A disintegrin and metalloprotease) family of transmembrane proteins, in particular Adam22. We found that Lgi4 and Adam22 are both expressed in Schwann cells as well as in sensory neurons and that Lgi4 binds directly to Adam22 without a requirement for additional membrane associated factors. To determine whether Lgi4-Adam22 function involves a paracrine and/or an autocrine mechanism of action we performed heterotypic Schwann cell sensory neuron cultures and cell type-specific ablation of Lgi4 and Adam22 in mice. We show that Schwann cells are the principal cellular source of Lgi4 in the developing nerve and that Adam22 is required on axons. Our results thus reveal a novel paracrine signaling axis in peripheral nerve myelination in which Schwann cell secreted Lgi4 functions through binding of axonal Adam22 to drive the differentiation of Schwann cells.post to: CiteULike

Publication Date: 2010 Mar 10 PMID: 20220017Authors: Sullivan, E. L. - Grayson, B. - Takahashi, D. - Robertson, N. - Maier, A. - Bethea, C. L. - Smith, M. S. - Coleman, K. - Grove, K. L.Journal: J NeurosciChildhood obesity is associated with increased risk of behavioral/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder. As the majority of women of child-bearing age are overweight or obese and consume a diet high in dietary fat, it is critical to examine the consequences of maternal overnutrition on the development of brain circuitry that regulates offspring behavior. Using a nonhuman primate model of diet-induced obesity, we found that maternal high-fat diet (HFD) consumption caused perturbations in the central serotonergic system of fetal offspring. In addition, female infants from HFD-fed mothers exhibited increased anxiety in response to threatening novel objects. These findings have important clinical implications as they demonstrate that exposure to maternal HFD consumption during gestation, independent of obesity, increases the risk of developing behavioral disorders such as anxiety.post to: CiteULike

Networks — be they telecom, social, transportation or otherwise — are the fabric of modern society. They provide immense value to consumers and businesses alike, enhancing mutual relationships and enabling the distribution of goods, services and information. But does this value grow as the size of the networks grow? And if so, how much?

“Metcalfe’s Law” has long been accepted as characterizing the value — and value growth — of fully connected networks. It states that the value of a network is proportional to the square of the number of its nodes, which may take the form of devices — such as computers — or users, in which case a network connection is represented by a “friend” or “follower.” But there are times when the “law,” which has been used to explain network effects and justify mergers and acquisitions, appears to overstate a network’s value. And if that’s the case, what can service providers do about it?

While the number of possible connections in a network is indeed proportional to the square of the number of nodes, value is not necessarily equivalent to number. After all, I may have 10 bills in my wallet, but it matters a lot whether they are $1 or $10,000 denominations.

As I’ve previously observed (at Telecosm and via some math (PDF)), there are several reasons that Metcalfe’s Law can overestimate the value of a network. First, typically only a fraction of the possible connections have value. Second, there are natural limits to consumption of that value. And third, the value of the entire network may decline over time.

Convergent Value Distributions

The number of links in a fully connected network is certainly proportional to the square of the number of nodes. If each connection had the same value as any other, then Metcalfe’s Law would be correct. What would that mean in practice? It would mean that you would spend equal time on the phone with each of the nearly 7 billion people in the world, that they would all friend you or follow you, and you would reciprocate. But humans don’t behave that way.

In 1992, anthropologist Robin Dunbar posited that primates have neurobiologically-based limits to the size of their social networks. For humans, “Dunbar’s Number” is 150. This is exemplified by the fact that the most popular social networking site on the planet now has more than 400 million users, yet the average number of “friends” a person has is only 130 and only a small percentage of those “friends” actually communicate with one another. And although there are a variety of ways to slice the data, the largest microblogging site has close to 100 million users but the average number of followers is roughly 126. Even if we were to assume that tweets have the same “value” as intimate face-to-face interactions and that electronic media might expand Dunbar’s number in some way, there is still an upper bound to the number of relationships, or even weak ties, that can be maintained. If the total value of such social media is related to engagement, and engagement is related to the number of friends, such value would in these cases be linearly proportional to the size of the network, rather than the square of its size.

Intrinsic Limits of Consumption

Suppose you did have equal social interest in the nearly 7 billion people on the planet, or the more than 100 million shared video clips or even the more than 100,000 touchscreen phone apps out there. You then would run into intrinsic limits to your ability to benefit from all those relationships or consume all that content. Perhaps in the early days of TV it would have been possible for a single individual to consume all the content produced. Currently, however, nearly a day’s worth of content is uploaded to YouTube every minute. Assuming that all those clips did have equal value, even a multitasking insomniac couldn’t keep up. All networks have intrinsic upper limits of consumption, be they bandwidth or dollars or time or attention span.

Holistic Network Value Declines

Even if all nodes were of equal value, and there were no limits to consumption, well, people get jaded. Emotional rewards from novel stimuli are processed by dopamine receptors in the striatum, but the brain is designed to habituate, that is, not get so excited by repeated stimuli. What this means is that an entire social or content network may “grab” you at first, or even for a couple of years, but this infatuation may eventually wear off, and you’ll depart in search of the next new thing. Technological progress can also cause the value of the entire network to decay — consider what the web and email have done to the value of fax networks.

Strategies

There are ways to manage these three effects, however.

If the network node values follow a convergent distribution, ensure that whatever value is present can be extracted by reducing or eliminating core bottlenecks and enhancing the process of discovery. Specific approaches such as scalable non-blocking network infrastructure, content delivery networks, tagging, recommendation and search engines can help.

To extract maximum value when there are intrinsic limits of consumption, not only is removing access bottlenecks effective, but so are personalization, richness, context sensitivity and multitasking facilitation.

And to keep a given network exciting and the dopamine system revved up, new features, content or applications can help. Even if the core “network”— whether social site or app store — remains the same, using a platform for new content or apps can continue to trigger the pleasure receptors associated with novelty, maximizing value and engagement.

Overall, the behavior of real-world networks isn’t always as simple as what’s represented by Metcalfe’s Law. However, understanding their underlying characteristics can help users and service providers maximize their value as well as create new business opportunities.

Y'know, OnLive and Gaikai aren't the only game-streaming services on the block. OTOY has been laying low for a minute, but the "other" game streaming service has finally made its big announcement: it's going to release in Q2 2010. In fact, OTOY isn't just a service for streaming games; there are now claims of streaming movies, PC applications and "other graphically-intensive applications" to any mobile device with a web browser.

OTOY will employ AMD Fusion Render Cloud technology, a CPU/GPU server platform that will stream games straight into your see pee youz through the company's software suite. And if you have no idea what that means, check out a demo of the service right here, courtesy of TechCrunch -- basically, it's like playing games on your computer. What a novel idea!

[Via Big Download]

OTOY to launch in 'Q2 2010' through AMD partnership originally appeared on Joystiq on Fri, 12 Mar 2010 19:58:00 EST. Please see our terms for use of feeds.

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Y'know, OnLive and Gaikai aren't the only game-streaming services on the block. OTOY has been laying low for a minute, but the "other" game streaming service has finally made its big announcement: it's going to release in Q2 2010. In fact, OTOY isn't just a service for streaming games; there are now claims of streaming movies, PC applications and "other graphically-intensive applications" to any mobile device with a web browser.

OTOY will employ AMD Fusion Render Cloud technology, a CPU/GPU server platform that will stream games straight into your see pee youz through the company's software suite. And if you have no idea what that means, check out a demo of the service right here, courtesy of TechCrunch -- basically, it's like playing games on your computer. What a novel idea!

[Via Big Download]

OTOY to launch in 'Q2 2010' through AMD partnership originally appeared on Joystiq on Fri, 12 Mar 2010 19:58:00 EST. Please see our terms for use of feeds.

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A few brave souls use their fierce talent to recreate beloved works of art page by page or scene by scene. One such artist is Zak Smith, whose impressive book -- Pictures Showing What Happens on Each Page of Thomas Pynchon's Novel Gravity's Rainbow -- does just that. There have also been plenty of cartoons of bunnies acting out movies like The Shining, Alien, and even Brokeback Mountain in 60 seconds, but I am fairly certain I've never seen anything quite like this panel-by-panel recreation of The Wicker Man with the Muppets.

Kermie plays naive Sergeant Howie, while Miss Piggy is naturally the sexy gal Willow, played originally by Britt Ekland with butt-slappin' zest. (There's even a shot of Ekland's nude torso with Miss Piggy's body attached. Gasp!) The best part? Gonzo takes over from Christopher Lee as Lord Summerisle. This is some truly inspired stuff, folks.

Unlike, say, the Nicolas Cage remake. Embedded after the jump is both the entire comic (!) and the best scenes from Nic Cage's version of The Wicker Man, which apparently consists of him punching a woman while dressed as a bear. "Not the bees!"

Enjoy and TGIF.

[Via the always-awesome Dangerous Minds]

Filed under: Fandom, Trailers and Clips

Continue reading The Muppets Do 'The Wicker Man'

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Two years ago, we launched Structure, our conference devoted to Internet infrastructure and cloud computing. At the time, it was clear as a sunny California day that the Internet was entering a brand-new phase of growth that would see everything from pipes to routers to web services scale up, all thanks to digitization. The emergence of cloud-based services such as Amazon’s EC2 and S3 was the first sign of this big shift.

Greg Papadopoulos (Sun) and Werner Vogels (Amazon) on stage at Structure 2009

Since then a lot has changed — and Structure has become a premier event for those of us who are deeply interested in Internet infrastructure and its business implications. And while it’s easy to get fixated on cloud computing, one cannot deny the far-reaching impact of on-demand and utility computing. However, to view cloud computing in isolation is a mistake. We need to think of infrastructure in a more holistic fashion.

Take big data, for example. One of the biggest changes we’re seeing is that companies are starting to look deeply into the data they’ve spent years collecting in order to figure out ways to leverage it. I have often talked about the coming data deluge and how it influences the demand for pretty much everything.

Attendees in the audience at Structure 2009 in San Francisco California.

From the emergence of private and hybrid clouds to the rise of novel server architectures to the importance of security in the cloud — these will be just some of the topics of discussion at our event. We’re also going to be exploring the impact of big data and real-time computing on infrastructure. What, for example, are the needs of the new, web-connected, on-demand enterprise?

Essentially, the 2010 edition of Structure is going to be about the progress the industry has made so far and how things are expected to evolve in the years to come. The event will be held on June 23 and 24th at the Mission Bay Conference Center in San Francisco.

Many of our old friends, such as Marc Benioff, CEO of Salesforce.com, and Amazon’s CTO Werner Vogels will be returning for the event. Other experts will join us for the first time — folks such as IBM’s Erich Clementi, who is spearheading Big Blue’s cloud computing efforts. We will be announcing more additions to the line-up of speakers in coming weeks.

The event is being expanded to two days so we can explore more topics and address one of our community’s biggest demands: more time to network. I hope you will come and be part of our ongoing conversation. Tickets are on sale now — at a discount. For more details, visit the Structure 2010 web site. See you in June!

Scientists want to study whale diseases, but collecting blood is difficult and dangerous to the scientists and the whales. But whale snot is also good for analyzing whale health, and whales shoot it out of their blowholes freely and frequently. The trick is in collecting it. Dr. Karina Acevedo-Whitehouse of the Zoological Society of London things remote control helicopters are the answer. Her recent paper in Animal Conservation (abstract), irresistibly entitled "A novel non-invasive tool for disease surveillance of free-ranging whales and its relevance to conservation programs," introduces the ground-breaking methodology of strapping a petri dish to a toy RC helicopter and flying it into the spout. Collect whale snot using an RC helicopter (Via Make: Online) Previously:Curiosity shop in a whale's belly Ancient weapon discovered in whale Whale attacks trainer at SeaWorld Whale meat sold by the can in Japan Sperm whale video Some whales double their weight when straining sea-water Stealthy anti-whaling powerboat what is it like to cut up a whale?...

Brightkite is tricky. Tricky and smart.

While larger than most of their location-based rivals with over 2 million users, they know that in the past year they’ve lost some momentum to the newer check-in services like Foursquare and Gowalla. So they’re trying to do something unique to swing momentum back in their favor.

Today, at the SXSW festival in Austin, Texas, Brightkite is unveiling its new Group Text service. It’s both a feature on the website and a standalone application in the App Store (it should be available shortly). With it, Brightkite is latching onto one of the most popular and fast growing categories in mobile applications: group texting. Unlike regular text messaging, this type of app allows you to message many people all at once (and go back and forth). And better, in a world where cell providers are still managing to rip-off users with their text message bundles or $0.15 rate per-text, group texting is absolutely free.

Services such as textPlus have already made the functionality very popular on the iPhone, and now Brightkite hopes that will translate into converting different types of users over to its core location-based service. The reason is that built-in to the Brightkite Group Text app is the core Brightkite functionality itself. While it’s a bit buried to the left hand side of the menu, you can both check-in at venues, and get check-in updates from other users in the app.

It’s a smart play. As other location services such as MyTown have proven, there’s a market to get users outside of the traditional early-adopter crowd into location by doing something novel (in their case, a straight-up Monopoly-type game). Group texting users seem to be rabid about the software, so why not give them a little location-based bonus to play around with if they desire?

At the same time, this app provides a nice compliment to the Brightkite service itself. With it, users get another social outlet to communicate with, sending messages or pictures, and having them threaded both in the app and online. And yes, it still works with traditional SMS messaging, as Brightkite was lucky enough to be granted a texting shortcode (41414) and it can work with these threaded conversations. For example:

By adding three digits to the end of the code, each person can now have 100 simultaneous threaded text conversations running on their phone.
41414-001 = conversation 1
41414-002 = conversation 2

And thanks to the SMS support, you can contact anyone in your address book, not just those using the app.

The service is now live on Brightkite’s site, and look for it later today in the App Store.

CrunchBase InformationBrightkiteInformation provided by CrunchBase

You may think that James Whale's 1931 Frankenstein film starring Boris Karloff is your first look at the monster, while in fact Thomas Edison's 1910 short adaptation of Mary Shelley's novel is its first true incarnation (and also the first ever horror film). March 18 marks the 100th anniversary of the release of the long forgotten original made in 1910 by Thomas Edison's studio, and to celebrate publisher BearManor Media is releasing Frederick C. Wiebel, Jr.'s new book "Edison's Frankenstein," along with a restored DVD of the original short (from the one existing print!). While you can read all about this gem over at the Hollywood Reporter, reading on you'll find the actual short for your viewing pleasure. It'll make you want to pick up the restored version, that I know for sure.

Publication Date: 2010 Mar 11 PMID: 20220837Authors: Moore, J. E.Journal: NatureCertain insulators have exotic metallic states on their surfaces. These states are formed by topological effects that also render the electrons travelling on such surfaces insensitive to scattering by impurities. Such topological insulators may provide new routes to generating novel phases and particles, possibly finding uses in technological applications in spintronics and quantum computing.post to: CiteULike

Lately we've had lots of folks writing in seeking practical advice on collecting tissue samples for use in studying whaleborne disease. I had no idea there were so many amateur cetopathologists out there!

Anyway, as you folks know--all too well, I'm sure--it is extremely difficult to collect blood from a wild whale without injuring or killing it in the process. However, and as even a child can tell you, the next best thing to live whale blood is live whale snot. Turns out it spews from their blowholes when they exhale, so the process is really very simple:

• Find whale.
• Hold petri dish over blowhole to intercept spout.
• Return to lab, enjoy sample.

Step 2 is actually the hard part. And although your first instinct may be to just jump in your rowboat, paddle out to a whale pod, lean way out over the side with your sample container, and wait, that's actually not as safe as it might sound. Each year, untold millions of scientists die attempting this maneuver. Their sun-bleached bones litter beaches all along the Pacific coast.

Enter Dr. Karina Acevedo-Whitehouse, of the Zoological Society of London. Her recent paper in Animal Conservation (abstract), irresistibly entitled "A novel non-invasive tool for disease surveillance of free-ranging whales and its relevance to conservation programs," introduces the ground-breaking methodology of strapping a petri dish to a toy RC helicopter and flying it into the spout. This landmark work stands not only to revolutionize our understanding of whale disease, but to save countless lives, and establishes Dr. Acevedo-Whitehouse as a serious contender for this year's (Ig) Nobel Prize.

[via The Thoughtful Animal]

P.S. Dr. Acevedo-Whitehouse, you are made of awesome. And although I have never met you and probably never will, I love you with all my heart.

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Molecular and Cellular Endocrinology (21 December 2009)

Puberty, as the end-point of a complex series of maturational events affecting the components of the hypothalamic-pituitary-gonadal (HPG) axis, is gated by the state of body energy reserves and sensitive to different metabolic cues; conditions of severe metabolic stress and energy unbalance (from anorexia to morbid obesity) being commonly linked to perturbation of the onset of puberty. In the last two decades, the neuroendocrine mechanisms responsible for the tight coupling between energy homeostasis and puberty onset have begun to be deciphered. These seemingly involve a plethora of metabolic hormones and neuropeptides, which impinge and integrate (mostly) at the hypothalamic centers governing reproduction. Yet, characterization of the mechanisms of action of such regulators (and even their nature and physiological relevance) still remains incomplete. In this review, we will summarize some recent developments in our knowledge of the effects and mechanisms of action of two key metabolic hormones, leptin and ghrelin, in the control of puberty onset. In addition, the roles of the hypothalamic Kiss1 system in the metabolic gating of puberty will be reviewed, with special attention to its regulation by leptin and the recent identification of the putative roles of Crtc1 and mTOR signaling as molecular conduits for the metabolic control of Kiss1 expression. Elucidation of these novel players and regulatory mechanisms will help for a better understanding of the determinants of the timing of puberty, and its eventual alterations in adverse metabolic conditions.
Juan Roa, David García-Galiano, Juan Castellano, Francisco Gaytan, Leonor Pinilla, Manuel Tena-Sempere

Almost every Richard Thompson song could be subtitled, "Watch out!" You never know where it's going next and you always have to be wary, even when he's having fun. Thompson is as familiar with the dark end of the street as any songwriter, he's a singer of uncommon emotion, and as a character in High Fidelity, the first novel by closet rock critic Nick Hornby, notes, he's "England's finest electric guitarist." Thompson is both tasteful and wild; one of three (so far) overlapping box sets of his recordings includes a disc labelled "Epic Live Workouts" that includes precisely zero wankery. "For Shame of Doing Wrong" is one of Thompson's strongest compositions. It began life on Pour Down Like Silver, one of the '70s recordings he co-headlined with Linda Thompson, they recorded it again for the sessions they abandoned in favor of the Joe Boyd-overseen Shoot Out the Lights (a strong candidate for Greatest Album of All Time of the Day), and this version, recorded live in 1985, is Thompson at his best. The lyrics overflow with regret without turning maudlin, the band rocks, and the only thing wrong with the extended guitar solo is that it isn't long enough. Enjoy!...

Publication Date: 2010 Mar 10 PMID: 20220003Authors: Gerasimenko, Y. - Gorodnichev, R. - Machueva, E. - Pivovarova, E. - Semyenov, D. - Savochin, A. - Roy, R. R. - Edgerton, V. R.Journal: J NeurosciThe degree of automaticity of locomotion in primates compared with other mammals remains unclear. Here, we examine the possibility for activation of the spinal locomotor circuitry in noninjured humans by spinal electromagnetic stimulation (SEMS). SEMS (3 Hz and 1.3-1.82 tesla) at the T11-T12 vertebrae induced involuntary bilateral locomotor-like movements in the legs of individuals placed in a gravity-neutral position. The formation of locomotor-like activity during SEMS started with a latency of 0.68 +/- 0.1 s after delivering the first stimulus, unlike continuous vibration of muscles, which requires several seconds. The first EMG burst in response to SEMS was observed most often in a proximal flexor muscle. We speculate that SEMS directly activates the circuitry intrinsic to the spinal cord, as suggested by the immediate response and the electrophysiological observations demonstrating an absence of strictly time-linked responses within the EMG burst associated with individual stimuli during SEMS. SEMS in the presence of vibration of the leg muscles was more effective in facilitating locomotor-like activity than SEMS alone. The present results suggest that SEMS could be an effective noninvasive clinical tool to determine the potential of an individual to recover locomotion after a spinal cord injury, as well as being an effective rehabilitation tool itself.post to: CiteULike