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I've always thought the music on the tv series The Mentalist is interesting and suitable. I noticed the music credit and was curious so I looked the guy up.
http://www.blakeneely.com/home.php
Friday, September 30, 2011
Sunday, September 25, 2011
Blizzard to implement real money, player-driven online Auction House
http://pc.ign.com/articles/118/1185020p1.html
From the article:
As easy as it is to become obsessed with the World of Warcraft Auction House, waiting for item prices to drop and putting up rare treasures for bidding with the hopes of pulling in a nice virtual profit, that's child's play compared to what Blizzard's doing with Diablo III. The online Auction House to be implemented through Battle.net for Blizzard's upcoming action-role-playing game will allow you to put in-game items up for sale for real money. You set the price, other players bid or buy out, you make the profit.
That means when you're in a dungeon, slay a boss and get a super rare item, it's exciting not only because it'll help you kill stuff more effectively, but also because you could potentially profit from it in real life. The Battle.net Auction Houses will be separated based on region. While there won't be one single Auction House for the global player base, all players within a region will have access to the same one. Eventually Blizzard may allow players to check auction houses in other regions using different currencies, but at launch that won't be the case.
Diablo III Beta Video Preview
Auction Houses will be split into in-game currency versions and real money versions. If you don't want to deal with using real funds to buy items (or virtual), you don't have to. Most of everything you find in Diablo III, from skill-enhancing runestones to rare items to in-game gold can be put up for auction. The system is Blizzard's way of taking ownership over the black markets that tend to pop up around item-based games.
It's also Blizzard's way of making more money. There'll be a "nominal" flat fee charged by Blizzard for every item you post on the Auction House, as well as a transaction fee when the item is sold. It's important to note that this is a fixed fee, so it does not scale depending on the rarity of what you're selling or the associated price. For those who might cry foul at this, Diablo III executive producer Rob Pardo points out, "We could have chosen to do a model of 'we're just going to sell rare items on our website for X amount of money'. We just didn't feel like that was the right decision for us." The reason Blizzard says the listing fee exists is to guard against players spamming the Auction House with junk. It's likely at launch you will get a handful of free listings per week to try it out.
Demon hunter, day trader.
Is Blizzard expecting the Auction House to serve as the primary source of revenue for Diablo III? "We're still sticking to our box model for Diablo," says Pardo. "When you look at the Auction House, it's a really big unknown. I think it has potential. I think it's really conducive to the design of Diablo." In case you're not aware, enemies in Diablo III drop random items. Unlike something like World of Warcraft where loot tables for bosses are well known, nothing in the world of Diablo will spill out items with any sort of reliability, and very few items you acquire in Diablo will be soulbound (permanently tied to your in-game character).
"If you look in the Western world," said Pardo, "box sales work perfectly fine and make a lot of sense. If you look more at the Eastern side, especially mainland Asia, they already have a different business model. We can't really sell boxes there. We already feel awkward because we're trying to force something over there. [The Auction House] could be the primary way of generating the right revenue for the Diablo franchise. Maybe in the future we go full free-to-play like League of Legends. All that's really unknown. But it's all possible."
Adventuring for profits.
If you buy an item online, you're free to do whatever you want with it. You can use it, trade it to a friend in-game, or wait for a 24-hour cooldown and put it right back up for sale with the hope of selling it for more than the original purchase price. The money you make on the Diablo III auction house can be filtered to a Blizzard account, where it can be used to buy other Blizzard products, or filtered through a as of yet unnamed third-party service into an external account, in which case it's your money to use however you see fit. There will be a percentage fee for exporting the money beyond the bounds of Blizzard's system, though, so you'll take a hit on your total revenue.
If you do decide to keep the money in Blizzard's system, you can't export it afterwards. "If we have a balance that you can at any point turn into cash," said Pardo, "we get treated like a bank. That suddenly brings in a whole lot more regulations and things we do and oversight we have to have. It just made so much more sense for us to partner with someone that does all that." The decision about whether to filter profits to the third-party account or the Blizzard one therefore becomes all the more important.
Blizzard maintains it has no interest in posting items for sale within the Auction House. The idea is for the whole system to be player-run, with Blizzard's oversight meant to serve as a guarantee that you will receive the items that you buy and receive the money earned for a successful sale. As of now Blizzard has no plans to separate players online between those using the in-game currency Auction House and those actively utilizing real-money transactions.
I'm sure, especially when Diablo III initially launches, item prices are going to be all over the place. But Blizzard is confident the prices will eventually balance out given the large number of players that will have access to each Auction House. "People are going to experiment and they're going to try things out," said Pardo. "Very quickly, the market will correct. You look at something like the iPhone App Store. When it first came out, it didn't take too long before you really saw there being tiers of pricing. I think that's going to happen exponentially more rapidly in an auction house with thousands of players all putting stuff up every other second."
As part of Blizzard's plan to provide a secure trading environment, Diablo III will require a constant online connection whether you're playing alone, with friends or competing in player-versus-player matches. Your characters will all be stored on Blizzard's servers to ensure there isn't any hacking going on, ideally maintaining a safe, secure environment.
Quest for cool items, or just buy them.
In many loot games, ninja looting, or greedily snatching up powerful items so others can't collect them, is frequently an issue. Thankfully, the issue of ninja looting is bypassed entirely in Diablo III. When playing with another, the loot you see onscreen is unique to you. That includes money and gear. You still fight the same monsters, interact with the same NPCs and travel through the same spaces, but the drops are visible and accessible only to you. So even if someone really, really wanted to snatch up gear before you get a chance while playing co-op, they couldn't.
Sellers on the Auction House will be anonymous anyway, so even if you know a particular player is a jerk, you won't be able to identify what he or she is selling. You will see the name of the player with the highest bid, but that's it, along with the item and potential buyout price. You can then set your account to bid up to auto-bid up to a certain limit on an item, meaning you don't have to hang around for an auction's duration.
What you won't be able to do, at least at launch, is preview the item's look on your character model. You also won't initially be able to access the Auction House through external websites or mobile devices, though this could change as well. Characters from your account, which will be capped at 10 on Battle.net, could potentially be sold at a later date, but it won't be possible whenever Diablo III is first pushed live.
Blizzard first started working on a real money Auction House for Diablo III around 18 to 24 months ago. "Even before StarCraft II you saw the landscape changing, especially in Asia first," said Pardo. "There are so many innovative business models and ideas that have been coming over to the States. What we realized was, no one's actually done this before. There's examples sort of like it. But there wasn't anyone that's done exactly what we're trying to do."
Welcome to your new office?
So has the knowledge that players will be turning around and selling items online affected the game's design at all? "It's an emphatic no," said Pardo. "What we're incentivized to do is make lots of awesome random items. If we were making Diablo III without the auction house, that's exactly the same goal we would have."
For now, Blizzard wants to take a hands-off approach to the market. But might there be any scenario where Blizzard would step in? "It's hard to speculate on what that thing would be. I think we really want this to be a player-driven economy. I don't think we want to be acting like the Federal Reserve trying to balance it. Our number one thing is to protect the fun an integrity of the game. If something happened, that I can't predict, that caused the Auction House to go off the rails and make the game worse to play, then yeah, we're going to have to do something. What I don't want to do is try to artificially manipulate prices or transactions or anything like that. That I want to say away from. The player economy is the player economy."
There's still no specific release date for Diablo III or its beta testing period, but it's hard to imagine anyone being less excited about the game considering this news. What do you think of how Blizzard is redefining the loot drop?
Saturday, September 24, 2011
3D Printing via evolving design
http://youtu.be/tQ6msb7eEeA
http://www.newscientist.com/blogs/onepercent/2011/08/evolve-your-own-objects-for-3d.html
Evolve your own objects for 3D printing
13:13 19 August 2011
Crowdsourcing
Internet
Jacob Aron, technology reporter
Want to get into 3D printing, but lack the skills to make your designs a reality? No matter - you can now create 3D objects in just a few clicks with EndlessForms, which uses evolutionary principles to gradually modify designs then brings them into the real world with 3D printing.
The site was created by a team of researchers at Cornell University in Ithaca, New York led by Hod Lipson, who recently explained how 3D printing is bringing about a second industrial revolution. The technology has the potential to democratise production, but users need an easy way to create designs without the need for complicated software.
EndlessForms lets you start with a basic shape then evolve it by selecting simple variants or combining it with other shapes to create your ideal design. Users can then share and rate their designs on the site, allowing others to use them as basis for their own designs or request them to be 3D-printed in a variety of materials. Popular objects created on the site so far include a lamp, a mushroom and a butterfly, and each object's page records its evolutionary history so you can go back and see how it was created.
In addition to bring 3D printing to the masses, the researchers hope their site will also help them learn more about the evolutionary model that powers it.
Their long-term goal is to create robots that can evolve like biological creatures, so EndlessForms is designed to explore what kind of biological body shapes the model can produce. Forget designing your own objects - what about 3D-printed pets?
--
Endlessforms.com
http://www.technologyreview.com/computing/38433/page1/
3-D Design Simplified
A new website could accelerate the adoption of 3-D printing.
Thursday, August 25, 2011
By Stephen Cass
Researchers at Cornell University have launched EndlessForms, a website that lets users create sculptures virtually and render them in physical form. The site demonstrates a technology that designers could use to create new products and accelerate the broader adoption of 3-D printing.
People can use EndlessForms without any prior 3-D design experience. The user begins by choosing an object from a randomly generated gallery. The site creates a new gallery of variants of the chosen object, and the user selects one of the variants. The process repeats, gradually refining the design into the shape the user desires. Users can share this shape with other users and, if they wish, send the object to a 3-D printing service to render it in a variety of materials, including plastic, silver, and gold-plated steel. A five-to-seven-centimeter plastic model typically costs less than $10.
Jeff Clune, a postdoctoral fellow at Cornell and the project lead, believes this approach is a critical advance over earlier attempts to produce objects and shapes through digital mutation and selection. Those attempts produced things that "just don't look that natural," says Clune. "So we went and stole the secrets that biological evolution took millions of years to discover." According to Clune, generating objects in this way automatically gives them useful properties such as symmetry, and when these objects are printed in 3-D, they usually turn out to be structurally sound.
The rules EndlessForms uses to generate objects and their variants resemble those of developmental biology—the study of how DNA instructions unfold to create an entire living organism. "Embryos create patterns in the form of chemical gradients," says Clune. Chemical gradients—changes in the concentrations of particular molecules—control which parts of an embryonic organism's genome are expressed. "There might be a simple linear gradient, like head to tail, or there might be might be a repeating gradient, like that which governs the creation of segments in a caterpillar," says Clune. Combining a head-to-tail, front-to-back, and repeating gradient, for example, creates the basic body plan of vertebrates.
Rather than simulating chemical gradients, EndlessForms stores a "genome" for each object that describes a collection of simple mathematical functions analogous to these gradients, so that, for example, a sine function takes the place of a repeating chemical gradient. The website produces variations on objects by mutating this mathematical DNA. By summing the contributions from all the functions described by the genome, and checking whether the result is above a threshold value, EndlessForms determines whether blocks of 3-D space called voxels are either filled or left empty in an object.
Currently, EndlessForms can generate only a limited range of novelty shapes. To contain computational costs, the system uses a relatively small number of voxels for each object. And because each object is initially randomly generated, a user with a specific shape in mind may need to do quite a bit of selecting and evolving to produce something close to that shape. However, the Cornell group and collaborators plan to develop the system to enable a user to input a 3-D scan of an existing object and then evolve variants from that. This would allow, for example, a designer to scan in a pair of sunglasses and use the system to evolve new styles.
The technology is "very impressive," says Neri Oxman, director of the MIT Media Lab's Mediated Matter research group. She believes the user-friendliness of the evolutionary approach could help drive the broader adoption of 3-D printing technologies, similar to how easy-to-use image editors fueled the growth of digital photography and graphic manipulation. "People could scan their own toothbrushes or other objects and evolve various designs of such items for members of their family," says Oxman, noting that this could ultimately have an impact on design similar to the impact that blogs and social media have had on journalism, opening the field to the general public.
http://www.newscientist.com/blogs/onepercent/2011/08/evolve-your-own-objects-for-3d.html
Evolve your own objects for 3D printing
13:13 19 August 2011
Crowdsourcing
Internet
Jacob Aron, technology reporter
Want to get into 3D printing, but lack the skills to make your designs a reality? No matter - you can now create 3D objects in just a few clicks with EndlessForms, which uses evolutionary principles to gradually modify designs then brings them into the real world with 3D printing.
The site was created by a team of researchers at Cornell University in Ithaca, New York led by Hod Lipson, who recently explained how 3D printing is bringing about a second industrial revolution. The technology has the potential to democratise production, but users need an easy way to create designs without the need for complicated software.
EndlessForms lets you start with a basic shape then evolve it by selecting simple variants or combining it with other shapes to create your ideal design. Users can then share and rate their designs on the site, allowing others to use them as basis for their own designs or request them to be 3D-printed in a variety of materials. Popular objects created on the site so far include a lamp, a mushroom and a butterfly, and each object's page records its evolutionary history so you can go back and see how it was created.
In addition to bring 3D printing to the masses, the researchers hope their site will also help them learn more about the evolutionary model that powers it.
Their long-term goal is to create robots that can evolve like biological creatures, so EndlessForms is designed to explore what kind of biological body shapes the model can produce. Forget designing your own objects - what about 3D-printed pets?
--
Endlessforms.com
http://www.technologyreview.com/computing/38433/page1/
3-D Design Simplified
A new website could accelerate the adoption of 3-D printing.
Thursday, August 25, 2011
By Stephen Cass
Researchers at Cornell University have launched EndlessForms, a website that lets users create sculptures virtually and render them in physical form. The site demonstrates a technology that designers could use to create new products and accelerate the broader adoption of 3-D printing.
People can use EndlessForms without any prior 3-D design experience. The user begins by choosing an object from a randomly generated gallery. The site creates a new gallery of variants of the chosen object, and the user selects one of the variants. The process repeats, gradually refining the design into the shape the user desires. Users can share this shape with other users and, if they wish, send the object to a 3-D printing service to render it in a variety of materials, including plastic, silver, and gold-plated steel. A five-to-seven-centimeter plastic model typically costs less than $10.
Jeff Clune, a postdoctoral fellow at Cornell and the project lead, believes this approach is a critical advance over earlier attempts to produce objects and shapes through digital mutation and selection. Those attempts produced things that "just don't look that natural," says Clune. "So we went and stole the secrets that biological evolution took millions of years to discover." According to Clune, generating objects in this way automatically gives them useful properties such as symmetry, and when these objects are printed in 3-D, they usually turn out to be structurally sound.
The rules EndlessForms uses to generate objects and their variants resemble those of developmental biology—the study of how DNA instructions unfold to create an entire living organism. "Embryos create patterns in the form of chemical gradients," says Clune. Chemical gradients—changes in the concentrations of particular molecules—control which parts of an embryonic organism's genome are expressed. "There might be a simple linear gradient, like head to tail, or there might be might be a repeating gradient, like that which governs the creation of segments in a caterpillar," says Clune. Combining a head-to-tail, front-to-back, and repeating gradient, for example, creates the basic body plan of vertebrates.
Rather than simulating chemical gradients, EndlessForms stores a "genome" for each object that describes a collection of simple mathematical functions analogous to these gradients, so that, for example, a sine function takes the place of a repeating chemical gradient. The website produces variations on objects by mutating this mathematical DNA. By summing the contributions from all the functions described by the genome, and checking whether the result is above a threshold value, EndlessForms determines whether blocks of 3-D space called voxels are either filled or left empty in an object.
Currently, EndlessForms can generate only a limited range of novelty shapes. To contain computational costs, the system uses a relatively small number of voxels for each object. And because each object is initially randomly generated, a user with a specific shape in mind may need to do quite a bit of selecting and evolving to produce something close to that shape. However, the Cornell group and collaborators plan to develop the system to enable a user to input a 3-D scan of an existing object and then evolve variants from that. This would allow, for example, a designer to scan in a pair of sunglasses and use the system to evolve new styles.
The technology is "very impressive," says Neri Oxman, director of the MIT Media Lab's Mediated Matter research group. She believes the user-friendliness of the evolutionary approach could help drive the broader adoption of 3-D printing technologies, similar to how easy-to-use image editors fueled the growth of digital photography and graphic manipulation. "People could scan their own toothbrushes or other objects and evolve various designs of such items for members of their family," says Oxman, noting that this could ultimately have an impact on design similar to the impact that blogs and social media have had on journalism, opening the field to the general public.
Thursday, September 22, 2011
Boosting brain power with electrical stimulation
http://www.gizmag.com/electrical-brain-stimulation/19899/
By Darren Quick
05:05 September 21, 2011
With the possible exception of those affected by hyperthylmesia - a rare condition where a person has an extraordinary capability to recall events from their past - most of us wouldn't mind having our memory enhanced. That's just what appears to have happened to a group of mice when targeted areas of their brains were electrically stimulated. The treatment triggered an increase in the creation of new cells in the hippocampus, with experiment results suggesting the mice's spatial learning improved. The researchers responsible say the results could have implications for the treatment of memory disorders in humans.
A clinical treatment known as deep brain stimulation (DBS), which delivers electrical pulses to targeted areas of the brain, has been used with some success in the treatment of movement and affective disorders, such as Parkinson's disease, and has also been recently explored for treatment of a range of neurologic and psychiatric conditions, including major depression and Tourette syndrome. The findings of this new study led by Paul Frankland, PhD, of The Hospital for Sick Children (SickKids), suggests the treatment could also have applications for memory disorders.
Throughout our lives, new cells are born in parts of the hippocampus - an area of the brain that plays important roles in spatial navigation and the consolidation of information from short-term to long-term memory. It is one of the first regions of the brain to suffer damage in Alzheimer's disease, with memory problems and disorientation among the first symptoms.
Frankland and his colleagues found that subjecting the entorhinal cortex - a region of the brain that directly communicates with the hippocampus - of adult mice to one hour of electrical stimulation led to a two-fold increase in new cells in the hippocampus. Although the burst of new cells lasted for only about one week, the cells produced during this time developed normally and made connections with nearby brain cells.
To test whether the newly integrated cells produced changes in memory, six weeks later the researchers tested how well the mice learned to navigate onto a landing submerged in a small pool of water. Compared with mice that didn't receive the therapy, the DBS-treated mice spent more time swimming near the landing, which the researchers say suggests improved spatial learning.
The results of the study echo a previous study that saw patients receive a boost in math skills lasting up to six months after an electrical current was applied to their parietal lobe - a region of the brain crucial for numerical understanding.
The findings of this new DBS study are published in the September 21 issue of The Journal of Neuroscience.
By Darren Quick
05:05 September 21, 2011
With the possible exception of those affected by hyperthylmesia - a rare condition where a person has an extraordinary capability to recall events from their past - most of us wouldn't mind having our memory enhanced. That's just what appears to have happened to a group of mice when targeted areas of their brains were electrically stimulated. The treatment triggered an increase in the creation of new cells in the hippocampus, with experiment results suggesting the mice's spatial learning improved. The researchers responsible say the results could have implications for the treatment of memory disorders in humans.
A clinical treatment known as deep brain stimulation (DBS), which delivers electrical pulses to targeted areas of the brain, has been used with some success in the treatment of movement and affective disorders, such as Parkinson's disease, and has also been recently explored for treatment of a range of neurologic and psychiatric conditions, including major depression and Tourette syndrome. The findings of this new study led by Paul Frankland, PhD, of The Hospital for Sick Children (SickKids), suggests the treatment could also have applications for memory disorders.
Throughout our lives, new cells are born in parts of the hippocampus - an area of the brain that plays important roles in spatial navigation and the consolidation of information from short-term to long-term memory. It is one of the first regions of the brain to suffer damage in Alzheimer's disease, with memory problems and disorientation among the first symptoms.
Frankland and his colleagues found that subjecting the entorhinal cortex - a region of the brain that directly communicates with the hippocampus - of adult mice to one hour of electrical stimulation led to a two-fold increase in new cells in the hippocampus. Although the burst of new cells lasted for only about one week, the cells produced during this time developed normally and made connections with nearby brain cells.
To test whether the newly integrated cells produced changes in memory, six weeks later the researchers tested how well the mice learned to navigate onto a landing submerged in a small pool of water. Compared with mice that didn't receive the therapy, the DBS-treated mice spent more time swimming near the landing, which the researchers say suggests improved spatial learning.
The results of the study echo a previous study that saw patients receive a boost in math skills lasting up to six months after an electrical current was applied to their parietal lobe - a region of the brain crucial for numerical understanding.
The findings of this new DBS study are published in the September 21 issue of The Journal of Neuroscience.
Monday, September 19, 2011
HIV Gene Therapy, Vaccine
http://www.gizmag.com/spanish-hiv-vaccine-90-percent-immune-response/19973/
Researchers at the Spanish Superior Scientific Research Council (CSIC) have successfully completed Phase I human clinical trials of a HIV vaccine that came out with top marks after 90% of volunteers developed an immunological response against the virus. The MVA-B vaccine draws on the natural capabilities of the human immune system and "has proven to be as powerful as any other vaccine currently being studied, or even more", says Mariano Esteban, head researcher from CSIC's National Biotech Centre.
Dr. Mariano Esteban, head researcher from CSIC's National Biotech Centre (Image: CSIC)
Researchers at the Spanish Superior Scientific Research Council (CSIC) have successfully c...
Map illustrating the HIV virus as spread across the globe (Image: CSIC)
Three-dimensional model of a HIV virus particle (Image: CSIC)
The MVA-B vaccine first showed promising signs back in 2008 when clinical trials involving mice and macaque monkeys demonstrated a very high efficiency against Simian immunodeficiency virus (SIV). The recent human trials involved 30 healthy volunteers, where 24 were treated with MVA-B, while the other 6 were treated with a placebo, carried out over a 48 week period.
Development of MVA-B is based on the insertion of four HIV genes in a previously used vaccine (MVA) for smallpox. When injected with the vaccine, a healthy immune system can react against the MVA, whilst the HIV genes are incapable of self-replicating. This guarantees a safe clinical trial for HIV free volunteers. Furthermore by trialing the vaccine on healthy patients, the immune system can learn how to detect and combat the HIV virus components. "It is like showing a picture of the HIV so that it is able to recognize it if it sees it again in the future", says Esteban.
"Our body is full of lymphocytes, each of them programmed to fight against a different pathogen" continued Esteban. "Training is needed when it involves a pathogen, like the HIV one, which cannot be naturally defeated".
The trial demonstrated how the vaccine stimulates the production of lymphocytes B, which produces HIV attacking antibodies that block the virus from infecting healthy cells. Blood tests during the 48th week revealed that 72.7% of the treated volunteers had developed these HIV fighting antibodies. However generating a long lasting response against future attacks truly renders the vaccine effective. This is achieved when the body maintains a basic memory level of T lymphocytes, which are generated after the first attack and can circulate the body for years. The T lymphocytes are responsible for stimulating the attacked cell's immune response, which can then identify and destroy the HIV virus. Blood tests during the 48th week revealed that the 85% of the patients maintained the memory T lymphocytes immune response.
"MVA-B immune profile meets, initially, the requirements for a promising HIV vaccine," says Esteban. Although it does not remove the virus from the body, the immune response induced by the vaccine could keep the virus under control by destroying the infected cell.
According to CSIC, "if this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays".
Phase I clinic trials will also commence with HIV infected volunteers to test its efficiency as a therapeutic vaccine.
Source: Spanish Superior Scientific Research Council (Spanish).
http://news.sciencemag.org/sciencenow/2011/09/gene-therapy-may-thwart-hiv.html?ref=hp
Gene Therapy May Thwart HIV
by Jon Cohen on 19 September 2011, 12:36 PM | 0 Comments
This past year, a Berlin man, Timothy Brown, became world famous as the first—and thus far only—person to apparently have been cured of his HIV infection. Brown's HIV disappeared after he developed leukemia and doctors gave him repeated blood transfusions from a donor who harbored a mutated version of a receptor the virus uses to enter cells. Now, researchers report promising results from two small gene-therapy studies that mimic this strategy, hinting that the field may be moving closer to a cure that works for the masses.
At the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, Illinois, this weekend, researchers reported preliminary results from tests of a novel treatment in 15 HIV-infected people designed to free them from the need to take antiretroviral drugs. The studies, conducted separately on the East and West coasts of the United States, attempt to make the immune system resistant to HIV by crippling a receptor, known as CCR5, on T cells that the virus uses during the infection process. The man who donated blood for Timothy Brown's transfusions had naturally defective CCR5 receptors.
The trial participants had T cells removed from their blood and then modified in the laboratory with a designer enzyme engineered by Sangamo BioSciences in Richmond, California. The enzyme, called a zinc finger nuclease, clips the gene for the CCR5 receptor and disables it. Ten billion modified cells were then reinfused into the participants' bodies, and the new data show that about 25% of cells had the mutant CCR5s. The studies found that modified T cells persisted for more than 6 months in several patients.
In one provocative case reported in Chicago yesterday, a patient who received the gene therapy and then stopped taking antiretroviral drugs had HIV return within a month, as typically happens when people interrupt their treatment. But a few weeks later, the virus began to decline, and it dropped to undetectable levels in concert with evidence that the gene therapy had altered his T cells. "Those kinetics are very different from what I've seen in treatment interruption studies, and we've done many," says Pablo Tebas, an infectious disease clinician at the University of Pennsylvania who heads the East Coast study of six participants. "This patient goes down, way down."
Tebas recognizes that his study is uncontrolled and that they've seen this response in only one patient. What's more, the patient already had a natural advantage because he has a crippled CCR5 gene in one of the two copies he inherited. Tebas suspects that the gene therapy coupled with his natural CCR5 mutation combined to lead to the dramatic result. "This is a very small experiment, and I don't think it's a cure by any means, but the Berlin patient is only one patient, and it changed research priorities," Tebas says. "This shows that there's a correlation between antiviral activity and the proportion of modified cells. It shows a path forward."
Although researchers do not expect the gene therapy to entirely clear HIV from the body, they hope it will create a "functional cure"—in other words, contain the virus to such a powerful extent that people no longer need antiretrovirals.
Virologist David Margolis, who is conducting his own HIV cure studies at the University of North Carolina, Chapel Hill, says many questions remain about the impact of this gene therapy, however. "These data are interesting, and encouraging, but still incomplete," he says. Yet Margolis is "impressed" by the percentage of cells that have the artificially modified CCR5 gene.
Even if this gene therapy proves itself, the cost and technical challenge of the intervention means it likely will have little chance of being used outside of wealthy countries. But Tebas notes that the cost of antiretrovirals also is high and that any calculation would have to balance one against the other.
http://www.medpagetoday.com/MeetingCoverage/ICAAC/28595
This report is part of a 12-month Clinical Context series.
By Michael Smith, North American Correspondent, MedPage Today
Published: September 19, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco. Earn CME/CE credit
for reading medical news
Action Points
Note that these studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that a gene-based treatment for HIV involving genetically modifying a patient's CD4-positive T cells was safe and well tolerated in two small clinical trials.
Note that the gene therapy resulted in increases in total CD4 counts in both studies.
CHICAGO -- A gene-based treatment for HIV was safe and well tolerated in two small clinical trials, and there are hints that the method is at least a first step toward a so-called "functional cure," researchers said here.
The method involves genetically modifying a patient's CD4-positive T cells -- the target of HIV -- so that they are resistant to the virus, according to Ronald Mitsuyasu, MD, of the University of California Los Angeles, who presented one of the industry-sponsored trials.
"If we can get [patients] to such a level that their own immune system can kick in and control the virus without drugs, that's a win," Mitsuyasu told MedPage Today at the Interscience Conference on Anti-Microbial Agents and Chemotherapy.
In one of the studies, something like that appears to have happened: After an infusion of modified cells, one patient saw his HIV viral load rise and then drop back to undetectable during a planned 12-week drug holiday.
"We never see that in treatment interruptions," Mitsuyasu said.
But the researchers reported that other patients in the study responded to stopped drug therapy with a predictable rise in HIV viral load, followed, in some cases, by a slight decline, but not to the undetectable level of fewer than 50 copies of viral RNA per milliliter of plasma.
The finding illustrates a key challenge, Mitsuyasu told MedPage Today: "We don't know what level of gene modification is adequate" to produce such a robust response, except that it appears to be higher than what they're getting in most patients.
The studies, which involved a total of 15 patients, are mainly looking at the safety of the process, in which CD4 cells are removed from the patient, modified so that they do not express a functional CCR5 receptor, and re-infused.
The CCR5 receptor is the main entry point for HIV, and people with a single genetic variation – the delta-32 mutation in the CCR5 gene – are resistant to HIV. Indeed, those with two copies of the mutated gene are almost immune while those with one copy have a slower disease course.
Mitsuyasu and colleagues are testing whether using genetic techniques to produce CCR5-deficient CD4 cells can lead to HIV treatments and perhaps a "functional cure," in which the patient still carries the virus, but no longer needs drugs to control it and prevent disease.
Several groups are at various stages of trying to modify the gene as a potential therapy, either by altering CD4 cells themselves or by changing blood stem cells. Mitsuyasu and his colleagues appear to be leading the pack at the moment.
In the process they use, Mitsuyasu said, about a third of the modified CD4 cells are "bi-allelic," carrying two modified genes that are nearly immune to HIV in principle. Other cells have a single copy and still others are not affected by the modification.
An Increase in CD4 Cells
Two studies presented here were:
A nine-patient dose-ranging study by Mitsuyasu's team, in which groups of three patients were given 10, 20, or 30 billion modified cells.
A six-patient study that included a 12-week treatment interruption 14 days after a dose of 10 billion cells. This study was led by Dale Ando, MD, at Sangamo Biosciences in Richmond, Calif.
In both studies, there were no serious adverse events, Mitsuyasu said. Most adverse events occurred in the first 24 hours after infusion and were apparently related to the infusion. These adverse events were mild or moderate, and resolved without sequelae.
In the larger study, Mitsuyasu said, patients were on highly active anti-retroviral therapy (HAART) and had an undetectable viral load, but despite a median of 21 years of treatment, they had fewer than 500 CD4 cells per milliliter of plasma.
The researchers found that in all cases the cells appeared to engraft and proliferate, persisting for at least a year both in plasma and in the rectal mucosa, without any apparent dose-response curve. Mitsuyasu also said that:
All patients saw increases in their CD4 cell count, with a median rise in plasma of 163 cells after six months. Not all patients are a year from treatment, but for those who are, the median rise is 100 cells.
The cells can be detected in the rectal mucosa a year after treatment, which demonstrates normal homing to the gut-associated lymphoid tissue, an important HIV reservoir.
The ratio between CD4 and CD8 cells normalized in all patients.
The smaller study enrolled six patients, again all on HAART and without detectable viral loads, but who had more robust immune systems, with a median of 974 CD4 cells per milliliter of plasma.
All were given 10 billion modified cells and 14 days later embarked on a 12-week drug holiday, the researchers reported.
As in the other study, patients saw increases in CD4 cells -- a median increase of 500 cells per milliliter after 150 days -- as well as a normalization of the CD4/CD8 ratio, and persistence of the cells in the blood.
The most striking finding came from the treatment interruption, during which all patients saw an initial HIV viral load increase in the absence of HAART. On the other hand, three patients saw their viral load drop again markedly, including the one whose virus became undetectable.
The patient was one of the people whose CD4 cells already carried one copy of the mutated CCR5 gene; the gene therapy meant that the proportion of re-infused cells carrying two copies was about twice as high as in the other patients.
The researchers said that one implication of their work is that in order to have a similar effect in others, they may need to find ways of increasing the proportion of modified cells that carry two copies of the modified CCR5 gene.
Ongoing Challenges
Indeed, the research probably means the number of modified cells is "more important than previously expected," commented Laurent Kaiser, MD, of the University Hospitals of Geneva, and a member of the conference's program committee.
And that highlights the technical and scientific challenges that still remain before the gene therapy can enter the clinic, Kaiser told MedPage Today.
It's important to remember that gene therapy in various forms has been tried for several years "and still we do not have very many examples where you can use cell-therapy to treat patients." On the other hand, "it's a way to move forward." he said.
The studies were supported by Sangamo Biosciences of Richmond, Calif. Mitsuyasu reported financial links with Sangamo, Janssen Biotechnology, and Merck. Several authors were employees of Sangamo.
Kaiser did not report any conflicts.
Primary source: Interscience Conference on Anti-Microbial Agents and Chemotherapy
Source reference:
Mitsuyasu R, et al "Adoptive transfer of zinc finger nuclease (ZFN) modified autologous CD4 T-cells to aviremic HIV-infected subjects with suboptimal CD4 counts" ICAAC 2011; Abstract H1-375.
Additional source: Interscience Conference on Anti-Microbial Agents and Chemotherapy
Source reference:
Ando D, et al "HAART treatment interruption following adoptive transfer of zinc finger nuclease (ZFN) modified mutologous CD4 T-cells (SB-728-T) to HIV-infected subjects demonstrates durable engraftment and suppression of viral load" ICAAC 2011; Abstract H2-794a.
Researchers at the Spanish Superior Scientific Research Council (CSIC) have successfully completed Phase I human clinical trials of a HIV vaccine that came out with top marks after 90% of volunteers developed an immunological response against the virus. The MVA-B vaccine draws on the natural capabilities of the human immune system and "has proven to be as powerful as any other vaccine currently being studied, or even more", says Mariano Esteban, head researcher from CSIC's National Biotech Centre.
Dr. Mariano Esteban, head researcher from CSIC's National Biotech Centre (Image: CSIC)
Researchers at the Spanish Superior Scientific Research Council (CSIC) have successfully c...
Map illustrating the HIV virus as spread across the globe (Image: CSIC)
Three-dimensional model of a HIV virus particle (Image: CSIC)
The MVA-B vaccine first showed promising signs back in 2008 when clinical trials involving mice and macaque monkeys demonstrated a very high efficiency against Simian immunodeficiency virus (SIV). The recent human trials involved 30 healthy volunteers, where 24 were treated with MVA-B, while the other 6 were treated with a placebo, carried out over a 48 week period.
Development of MVA-B is based on the insertion of four HIV genes in a previously used vaccine (MVA) for smallpox. When injected with the vaccine, a healthy immune system can react against the MVA, whilst the HIV genes are incapable of self-replicating. This guarantees a safe clinical trial for HIV free volunteers. Furthermore by trialing the vaccine on healthy patients, the immune system can learn how to detect and combat the HIV virus components. "It is like showing a picture of the HIV so that it is able to recognize it if it sees it again in the future", says Esteban.
"Our body is full of lymphocytes, each of them programmed to fight against a different pathogen" continued Esteban. "Training is needed when it involves a pathogen, like the HIV one, which cannot be naturally defeated".
The trial demonstrated how the vaccine stimulates the production of lymphocytes B, which produces HIV attacking antibodies that block the virus from infecting healthy cells. Blood tests during the 48th week revealed that 72.7% of the treated volunteers had developed these HIV fighting antibodies. However generating a long lasting response against future attacks truly renders the vaccine effective. This is achieved when the body maintains a basic memory level of T lymphocytes, which are generated after the first attack and can circulate the body for years. The T lymphocytes are responsible for stimulating the attacked cell's immune response, which can then identify and destroy the HIV virus. Blood tests during the 48th week revealed that the 85% of the patients maintained the memory T lymphocytes immune response.
"MVA-B immune profile meets, initially, the requirements for a promising HIV vaccine," says Esteban. Although it does not remove the virus from the body, the immune response induced by the vaccine could keep the virus under control by destroying the infected cell.
According to CSIC, "if this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays".
Phase I clinic trials will also commence with HIV infected volunteers to test its efficiency as a therapeutic vaccine.
Source: Spanish Superior Scientific Research Council (Spanish).
http://news.sciencemag.org/sciencenow/2011/09/gene-therapy-may-thwart-hiv.html?ref=hp
Gene Therapy May Thwart HIV
by Jon Cohen on 19 September 2011, 12:36 PM | 0 Comments
This past year, a Berlin man, Timothy Brown, became world famous as the first—and thus far only—person to apparently have been cured of his HIV infection. Brown's HIV disappeared after he developed leukemia and doctors gave him repeated blood transfusions from a donor who harbored a mutated version of a receptor the virus uses to enter cells. Now, researchers report promising results from two small gene-therapy studies that mimic this strategy, hinting that the field may be moving closer to a cure that works for the masses.
At the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, Illinois, this weekend, researchers reported preliminary results from tests of a novel treatment in 15 HIV-infected people designed to free them from the need to take antiretroviral drugs. The studies, conducted separately on the East and West coasts of the United States, attempt to make the immune system resistant to HIV by crippling a receptor, known as CCR5, on T cells that the virus uses during the infection process. The man who donated blood for Timothy Brown's transfusions had naturally defective CCR5 receptors.
The trial participants had T cells removed from their blood and then modified in the laboratory with a designer enzyme engineered by Sangamo BioSciences in Richmond, California. The enzyme, called a zinc finger nuclease, clips the gene for the CCR5 receptor and disables it. Ten billion modified cells were then reinfused into the participants' bodies, and the new data show that about 25% of cells had the mutant CCR5s. The studies found that modified T cells persisted for more than 6 months in several patients.
In one provocative case reported in Chicago yesterday, a patient who received the gene therapy and then stopped taking antiretroviral drugs had HIV return within a month, as typically happens when people interrupt their treatment. But a few weeks later, the virus began to decline, and it dropped to undetectable levels in concert with evidence that the gene therapy had altered his T cells. "Those kinetics are very different from what I've seen in treatment interruption studies, and we've done many," says Pablo Tebas, an infectious disease clinician at the University of Pennsylvania who heads the East Coast study of six participants. "This patient goes down, way down."
Tebas recognizes that his study is uncontrolled and that they've seen this response in only one patient. What's more, the patient already had a natural advantage because he has a crippled CCR5 gene in one of the two copies he inherited. Tebas suspects that the gene therapy coupled with his natural CCR5 mutation combined to lead to the dramatic result. "This is a very small experiment, and I don't think it's a cure by any means, but the Berlin patient is only one patient, and it changed research priorities," Tebas says. "This shows that there's a correlation between antiviral activity and the proportion of modified cells. It shows a path forward."
Although researchers do not expect the gene therapy to entirely clear HIV from the body, they hope it will create a "functional cure"—in other words, contain the virus to such a powerful extent that people no longer need antiretrovirals.
Virologist David Margolis, who is conducting his own HIV cure studies at the University of North Carolina, Chapel Hill, says many questions remain about the impact of this gene therapy, however. "These data are interesting, and encouraging, but still incomplete," he says. Yet Margolis is "impressed" by the percentage of cells that have the artificially modified CCR5 gene.
Even if this gene therapy proves itself, the cost and technical challenge of the intervention means it likely will have little chance of being used outside of wealthy countries. But Tebas notes that the cost of antiretrovirals also is high and that any calculation would have to balance one against the other.
http://www.medpagetoday.com/MeetingCoverage/ICAAC/28595
This report is part of a 12-month Clinical Context series.
By Michael Smith, North American Correspondent, MedPage Today
Published: September 19, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco. Earn CME/CE credit
for reading medical news
Action Points
Note that these studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that a gene-based treatment for HIV involving genetically modifying a patient's CD4-positive T cells was safe and well tolerated in two small clinical trials.
Note that the gene therapy resulted in increases in total CD4 counts in both studies.
CHICAGO -- A gene-based treatment for HIV was safe and well tolerated in two small clinical trials, and there are hints that the method is at least a first step toward a so-called "functional cure," researchers said here.
The method involves genetically modifying a patient's CD4-positive T cells -- the target of HIV -- so that they are resistant to the virus, according to Ronald Mitsuyasu, MD, of the University of California Los Angeles, who presented one of the industry-sponsored trials.
"If we can get [patients] to such a level that their own immune system can kick in and control the virus without drugs, that's a win," Mitsuyasu told MedPage Today at the Interscience Conference on Anti-Microbial Agents and Chemotherapy.
In one of the studies, something like that appears to have happened: After an infusion of modified cells, one patient saw his HIV viral load rise and then drop back to undetectable during a planned 12-week drug holiday.
"We never see that in treatment interruptions," Mitsuyasu said.
But the researchers reported that other patients in the study responded to stopped drug therapy with a predictable rise in HIV viral load, followed, in some cases, by a slight decline, but not to the undetectable level of fewer than 50 copies of viral RNA per milliliter of plasma.
The finding illustrates a key challenge, Mitsuyasu told MedPage Today: "We don't know what level of gene modification is adequate" to produce such a robust response, except that it appears to be higher than what they're getting in most patients.
The studies, which involved a total of 15 patients, are mainly looking at the safety of the process, in which CD4 cells are removed from the patient, modified so that they do not express a functional CCR5 receptor, and re-infused.
The CCR5 receptor is the main entry point for HIV, and people with a single genetic variation – the delta-32 mutation in the CCR5 gene – are resistant to HIV. Indeed, those with two copies of the mutated gene are almost immune while those with one copy have a slower disease course.
Mitsuyasu and colleagues are testing whether using genetic techniques to produce CCR5-deficient CD4 cells can lead to HIV treatments and perhaps a "functional cure," in which the patient still carries the virus, but no longer needs drugs to control it and prevent disease.
Several groups are at various stages of trying to modify the gene as a potential therapy, either by altering CD4 cells themselves or by changing blood stem cells. Mitsuyasu and his colleagues appear to be leading the pack at the moment.
In the process they use, Mitsuyasu said, about a third of the modified CD4 cells are "bi-allelic," carrying two modified genes that are nearly immune to HIV in principle. Other cells have a single copy and still others are not affected by the modification.
An Increase in CD4 Cells
Two studies presented here were:
A nine-patient dose-ranging study by Mitsuyasu's team, in which groups of three patients were given 10, 20, or 30 billion modified cells.
A six-patient study that included a 12-week treatment interruption 14 days after a dose of 10 billion cells. This study was led by Dale Ando, MD, at Sangamo Biosciences in Richmond, Calif.
In both studies, there were no serious adverse events, Mitsuyasu said. Most adverse events occurred in the first 24 hours after infusion and were apparently related to the infusion. These adverse events were mild or moderate, and resolved without sequelae.
In the larger study, Mitsuyasu said, patients were on highly active anti-retroviral therapy (HAART) and had an undetectable viral load, but despite a median of 21 years of treatment, they had fewer than 500 CD4 cells per milliliter of plasma.
The researchers found that in all cases the cells appeared to engraft and proliferate, persisting for at least a year both in plasma and in the rectal mucosa, without any apparent dose-response curve. Mitsuyasu also said that:
All patients saw increases in their CD4 cell count, with a median rise in plasma of 163 cells after six months. Not all patients are a year from treatment, but for those who are, the median rise is 100 cells.
The cells can be detected in the rectal mucosa a year after treatment, which demonstrates normal homing to the gut-associated lymphoid tissue, an important HIV reservoir.
The ratio between CD4 and CD8 cells normalized in all patients.
The smaller study enrolled six patients, again all on HAART and without detectable viral loads, but who had more robust immune systems, with a median of 974 CD4 cells per milliliter of plasma.
All were given 10 billion modified cells and 14 days later embarked on a 12-week drug holiday, the researchers reported.
As in the other study, patients saw increases in CD4 cells -- a median increase of 500 cells per milliliter after 150 days -- as well as a normalization of the CD4/CD8 ratio, and persistence of the cells in the blood.
The most striking finding came from the treatment interruption, during which all patients saw an initial HIV viral load increase in the absence of HAART. On the other hand, three patients saw their viral load drop again markedly, including the one whose virus became undetectable.
The patient was one of the people whose CD4 cells already carried one copy of the mutated CCR5 gene; the gene therapy meant that the proportion of re-infused cells carrying two copies was about twice as high as in the other patients.
The researchers said that one implication of their work is that in order to have a similar effect in others, they may need to find ways of increasing the proportion of modified cells that carry two copies of the modified CCR5 gene.
Ongoing Challenges
Indeed, the research probably means the number of modified cells is "more important than previously expected," commented Laurent Kaiser, MD, of the University Hospitals of Geneva, and a member of the conference's program committee.
And that highlights the technical and scientific challenges that still remain before the gene therapy can enter the clinic, Kaiser told MedPage Today.
It's important to remember that gene therapy in various forms has been tried for several years "and still we do not have very many examples where you can use cell-therapy to treat patients." On the other hand, "it's a way to move forward." he said.
The studies were supported by Sangamo Biosciences of Richmond, Calif. Mitsuyasu reported financial links with Sangamo, Janssen Biotechnology, and Merck. Several authors were employees of Sangamo.
Kaiser did not report any conflicts.
Primary source: Interscience Conference on Anti-Microbial Agents and Chemotherapy
Source reference:
Mitsuyasu R, et al "Adoptive transfer of zinc finger nuclease (ZFN) modified autologous CD4 T-cells to aviremic HIV-infected subjects with suboptimal CD4 counts" ICAAC 2011; Abstract H1-375.
Additional source: Interscience Conference on Anti-Microbial Agents and Chemotherapy
Source reference:
Ando D, et al "HAART treatment interruption following adoptive transfer of zinc finger nuclease (ZFN) modified mutologous CD4 T-cells (SB-728-T) to HIV-infected subjects demonstrates durable engraftment and suppression of viral load" ICAAC 2011; Abstract H2-794a.
Sunday, September 18, 2011
Electronic payments via mobile devices, digital currency
***
Notes:
1. Use of mobile payments allows for exchanges where no internet is available, but mobile networks exist. E.G. underdeveloped areas where there are tourists but lacking infrastructure.
2. Bitcoin, Square would allow for traceable exchanges, but raise questions about regulation of currency.
3. Raises a question about the economic impact of digital currency on the U.S. dollar and other global currencies and global exchanges.
https://squareup.com
http://en.wikipedia.org/wiki/Square_%28payment_service%29
I encountered a produce stand using an app/device called Square for running credit cards through an iPhone.
Square is an electronic payment service from the creator of Twitter (Jack Dorsey) that allows users in the U.S. to accept credit cards via mobile devices. Square charges 2.75% on each transaction. Square also allows for sending of paperless receipts via text or email and is available as a free app for iOS and Android OS.
The owner of the produce stand uses Square because it is cheaper than purchasing and running a register. He also mentioned that he originally used Square because the internet was not available in his area but he could reach the mobile network. Certainly, there are security concerns and questions have been raised about the climate of users who rely on Bitcoin or Square - particularly those who deal in cash-only exchanges. However, tuning in to the theme of the state of currencies, with alternatives heating up from the global economic crisis.
More on Bitcoin - coinciding with the issuing of Google Wallet, this is P2P, not B2B - Google has some P2B partners lining up, but solutions like Square or Bitcoin give control to the retailers and the consumer.
"Bitcoin transactions can represent many kinds of operations such as pure peer-to-peer escrow and deposits but user interface software for this advanced functionality is currently underdeveloped."
http://www.bitcoin.org
http://en.wikipedia.org/wiki/Bitcoin
http://www.npr.org/blogs/money/2011/08/24/138673630/what-is-bitcoin#more
Analysis of Bitcoin anonymity (concludes that it is not):
http://anonymity-in-bitcoin.blogspot.com/2011/07/bitcoin-is-not-anonymous.html
Google Wallet launch:
http://www.washingtonpost.com/business/technology/google-wallet-likely-launching-tomorrow/2011/09/18/gIQAtdkBdK_story.html
Notes:
1. Use of mobile payments allows for exchanges where no internet is available, but mobile networks exist. E.G. underdeveloped areas where there are tourists but lacking infrastructure.
2. Bitcoin, Square would allow for traceable exchanges, but raise questions about regulation of currency.
3. Raises a question about the economic impact of digital currency on the U.S. dollar and other global currencies and global exchanges.
https://squareup.com
http://en.wikipedia.org/wiki/Square_%28payment_service%29
I encountered a produce stand using an app/device called Square for running credit cards through an iPhone.
Square is an electronic payment service from the creator of Twitter (Jack Dorsey) that allows users in the U.S. to accept credit cards via mobile devices. Square charges 2.75% on each transaction. Square also allows for sending of paperless receipts via text or email and is available as a free app for iOS and Android OS.
The owner of the produce stand uses Square because it is cheaper than purchasing and running a register. He also mentioned that he originally used Square because the internet was not available in his area but he could reach the mobile network. Certainly, there are security concerns and questions have been raised about the climate of users who rely on Bitcoin or Square - particularly those who deal in cash-only exchanges. However, tuning in to the theme of the state of currencies, with alternatives heating up from the global economic crisis.
More on Bitcoin - coinciding with the issuing of Google Wallet, this is P2P, not B2B - Google has some P2B partners lining up, but solutions like Square or Bitcoin give control to the retailers and the consumer.
"Bitcoin transactions can represent many kinds of operations such as pure peer-to-peer escrow and deposits but user interface software for this advanced functionality is currently underdeveloped."
http://www.bitcoin.org
http://en.wikipedia.org/wiki/Bitcoin
http://www.npr.org/blogs/money/2011/08/24/138673630/what-is-bitcoin#more
Analysis of Bitcoin anonymity (concludes that it is not):
http://anonymity-in-bitcoin.blogspot.com/2011/07/bitcoin-is-not-anonymous.html
Google Wallet launch:
http://www.washingtonpost.com/business/technology/google-wallet-likely-launching-tomorrow/2011/09/18/gIQAtdkBdK_story.html
Wednesday, September 14, 2011
Immune System Trained to Kill Cancer
http://www.nytimes.com/2011/09/13/health/13gene.html?_r=1&pagewanted=all
By DENISE GRADY
Published: September 12, 2011
PHILADELPHIA — A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose.
Doctors removed a billion of his T-cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins.
At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst.
A few weeks later, the fevers were gone. And so was the leukemia.
There was no trace of it anywhere — no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells.
A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work.
“I have my life back,” he said.
Mr. Ludwig’s doctors have not claimed that he is cured — it is too soon to tell — nor have they declared victory over leukemia on the basis of this experiment, which involved only three patients. The research, they say, has far to go; the treatment is still experimental, not available outside of studies.
But scientists say the treatment that helped Mr. Ludwig, described recently in The New England Journal of Medicine and Science Translational Medicine, may signify a turning point in the long struggle to develop effective gene therapies against cancer. And not just for leukemia patients: other cancers may also be vulnerable to this novel approach — which employs a disabled form of H.I.V.-1, the virus that causes AIDS, to carry cancer-fighting genes into the patients’ T-cells. In essence, the team is using gene therapy to accomplish something that researchers have hoped to do for decades: train a person’s own immune system to kill cancer cells.
Two other patients have undergone the experimental treatment. One had a partial remission: his disease lessened but did not go away completely. Another had a complete remission. All three had had advanced chronic lymphocytic leukemia and had run out of chemotherapy options. Usually, the only hope for a remission in such cases is a bone-marrow transplant, but these patients were not candidates for it.
Dr. Carl June, who led the research and directs translational medicine in the Abramson Cancer Center at the University of Pennsylvania, said that the results stunned even him and his colleagues, Dr. David L. Porter, Bruce Levine and Michael Kalos. They had hoped to see some benefit but had not dared dream of complete, prolonged remissions. Indeed, when Mr. Ludwig began running fevers, the doctors did not realize at first that it was a sign that his T-cells were engaged in a furious battle with his cancer.
Other experts in the field said the results were a major advance.
“It’s great work,” said Dr. Walter J. Urba of the Providence Cancer Center and Earle A. Chiles Research Institute in Portland, Ore. He called the patients’ recoveries remarkable, exciting and significant. “I feel very positive about this new technology. Conceptually, it’s very, very big.”
Dr. Urba said he thought the approach would ultimately be used against other types of cancer as well as leukemia and lymphoma. But he cautioned, “For patients today, we’re not there yet.” And he added the usual scientific caveat: To be considered valid, the results must be repeated in more patients, and by other research teams.
Dr. June called the techniques “a harvest of the information from the molecular biology revolution over the past two decades.”
Hitting a Genetic Jackpot
To make T-cells search out and destroy cancer, researchers must equip them to do several tasks: recognize the cancer, attack it, multiply, and live on inside the patient. A number of research groups have been trying to do this, but the T-cells they engineered could not accomplish all the tasks. As a result, the cells’ ability to fight tumors has generally been temporary.
The University of Pennsylvania team seems to have hit all the targets at once. Inside the patients, the T-cells modified by the researchers multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer and then gradually diminished, leaving a population of “memory” cells that can quickly proliferate again if needed.
The researchers said they were not sure which parts of their strategy made it work — special cell-culturing techniques, the use of H.I.V.-1 to carry new genes into the T-cells, or the particular pieces of DNA that they selected to reprogram the T-cells.
The concept of doctoring T-cells genetically was first developed in the 1980s by Dr. Zelig Eshhar at the Weizmann Institute of Science in Rehovot, Israel. It involves adding gene sequences from different sources to enable the T-cells to produce what researchers call chimeric antigen receptors, or CARs — protein complexes that transform the cells into, in Dr. June’s words, “serial killers.”
Mr. Ludwig’s disease, chronic lymphocytic leukemia is a cancer of B-cells, the part of the immune system that normally produces antibodies to fight infection. All B-cells, whether healthy or leukemic, have on their surfaces a protein called CD19. To treat patients with the disease, the researchers hoped to reprogram their T-cells to find CD19 and attack B-cells carrying it.
But which gene sequences should be used to reprogram the T-cells, from which sources? And how do you insert them?
Various research groups have used different methods. Viruses are often used as carriers (or vectors) to insert DNA into other cells because that kind of genetic sabotage is exactly what viruses normally specialize in doing. To modify their patients’ T-cells, Dr. June and his colleagues tried a daring approach: they used a disabled form of H.I.V.-1. They are the first ever to use H.I.V.-1 as the vector in gene therapy for cancer patients (the virus has been used in other diseases).
The AIDS virus is a natural for this kind of treatment, Dr. June said, because it evolved to invade T-cells. The idea of putting any form of the AIDS virus into people sounds a bit frightening, he acknowledged, but the virus used by his team was “gutted” and was no longer harmful. Other researchers had altered and disabled the virus by adding DNA from humans, mice and cows, and from a virus that infects woodchucks and another that infects cows. Each bit was chosen for a particular trait, all pieced together into a vector that Dr. June called a “Rube Goldberg-like solution” and “truly a zoo.”
“It incorporates the ability of H.I.V. to infect cells but not to reproduce itself,” he said.
To administer the treatment, the researchers collected as many of the patients’ T-cells as they could by passing their blood through a machine that removed the cells and returned the other blood components back into the patients’ veins. The T-cells were exposed to the vector, which transformed them genetically, and then were frozen. Meanwhile, the patients were given chemotherapy to deplete any remaining T-cells, because the native T-cells might impede the growth of the altered ones. Finally, the T-cells were infused back into the patients.
Then, Dr. June said, “The patient becomes a bioreactor” as the T-cells proliferate, pouring out chemicals called cytokines that cause fever, chills, fatigue and other flulike symptoms.
The treatment wiped out all of the patients’ B-cells, both healthy ones and leukemic ones, and will continue to do for as long as the new T-cells persist in the body, which could be forever (and ideally should be, to keep the leukemia at bay). The lack of B-cells means that the patients may be left vulnerable to infection, and they will need periodic infusions of a substance called intravenous immune globulin to protect them.
So far, the lack of B-cells has not caused problems for Mr. Ludwig. He receives the infusions every few months. He had been receiving them even before the experimental treatment because the leukemia had already knocked out his healthy B-cells.
One thing that is not clear is why Patient 1 and Patient 3 had complete remissions, and Patient 2 did not. The researchers said that when Patient 2 developed chills and fever, he was treated with steroids at another hospital, and the drugs may have halted the T-cells’ activity. But they cannot be sure. It may also be that his disease was too severe.
The researchers wrote an entire scientific article about Patient 3, which was published in The New England Journal of Medicine. Like the other patients, he also ran fevers and felt ill, but the reaction took longer to set in, and he also developed kidney and liver trouble — a sign of tumor lysis syndrome, a condition that occurs when large numbers of cancer cells die off and dump their contents, which can clog the kidneys. He was given drugs to prevent kidney damage. He had a complete remission.
What the journal article did not mention was that Patient 3 was almost not treated.
Because of his illness and some production problems, the researchers said, they could not produce anywhere near as many altered T-cells for him as they had for the other two patients — only 14 million (“a mouse dose,” Dr. Porter said), versus 1 billion for Mr. Ludwig and 580 million for Patient 2. After debate, they decided to treat him anyway.
Patient 3 declined to be interviewed, but he wrote anonymously about his experience for the University of Pennsylvania Web site. When he developed chills and a fever, he said, “I was sure the war was on — I was sure C.L.L. cells were dying.”
He wrote that he was a scientist, and that when he was young had dreamed of someday making a discovery that would benefit mankind. But, he concluded, “I never imagined I would be part of the experiment.”
When he told Patient 3 that he was remission, Dr. Porter said, they both had tears in their eyes.
Not Without Danger to Patients
While promising, the new techniques developed by the University of Pennsylvania researchers are not without danger to patients. Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.
She developed severe breathing trouble 15 minutes after receiving the T-cells, had to be put on a ventilator and died a few days later. Apparently, a protein target on the cancer cells was also present in her lungs, and the T-cells homed in on it.
Researchers at Memorial Sloan Kettering Cancer in New York also reported a death last year in a T-cell trial for leukemia (also published in Molecular Therapy). An autopsy found that the patient had apparently died from sepsis, not from the T-cells, but because he died just four days after the infusion, the researchers said they considered the treatment a possible factor.
Dr. June said his team hopes to use T-cells against solid tumors, including some that are very hard to treat, like mesothelioma and ovarian and pancreatic cancer. But possible adverse reactions are a real concern, he said, noting that one of the protein targets on the tumor cells is also found on membranes that line the chest and abdomen. T-cell attacks could cause serious inflammation in those membranes and mimic lupus, a serious autoimmune disease.
Even if the T-cells do not hit innocent targets, there are still risks. Proteins they release could cause a “cytokine storm”— high fevers, swelling, inflammation and dangerously low blood pressure — which can be fatal. Or, if the treatment rapidly kills billions of cancer cells, the debris can damage the kidney and cause other problems.
Even if the new T-cell treatment proves to work, the drug industry will be needed to mass produce it. But Dr. June said the research is being done only at universities, not at drug companies. For the drug industry to take interest, he said, there will have to be overwhelming proof that the treatment is far better than existing ones.
“Then I think they’ll jump into it,” he said. “My challenge now is to do this in a larger set of patients with randomization, and to show that we have the same effects.”
Mr. Ludwig said that when entered the trial, he had no options left. Indeed, Dr. June said that Mr. Ludwig was “almost dead” from the leukemia, and the effort to treat him was a “Hail Mary.”
Mr. Ludwig said: “I don’t recall anybody saying there was going to be a remission. I don’t think they were dreaming to that extent.”
The trial was a Phase 1 study, meaning that its main goal was to find out whether the treatment was safe, and at what dose. Of course, doctors and patients always hope that there will be some benefit, but that was not an official endpoint.
Mr. Ludwig thought that if the trial could buy him six months or a year, it would be worth the gamble. But even if the study did not help him, he felt it would still be worthwhile if he could help the study.
When the fevers hit, he had no idea that might be a good sign. Instead, he assumed the treatment was not working. But a few weeks later, he said that his oncologist, Dr. Alison Loren, told him, “We can’t find any cancer in your bone marrow.”
Remembering the moment, Mr. Ludwig paused and said, “I got goose bumps just telling you those words.”
“I feel wonderful,” Mr. Ludwig said during a recent interview. “I walked 18 holes on the golf course this morning.”
Before the study, he was weak, suffered repeated bouts of pneumonia and was wasting away. Now, he is full of energy. He has gained 40 pounds. He and his wife bought an R.V., in which they travel with their grandson and nephew. “I feel normal, like I did 10 years before I was diagnosed,” Mr. Ludwig said. “This clinical trial saved my life.”
Dr. Loren said in an interview, “I hate to say it in that dramatic way, but I do think it saved his life.”
Mr. Ludwig said that Dr. Loren told him and his wife something he considered profound. “She said, ‘We don’t know how long it’s going to last. Enjoy every day,’ ” Mr. Ludwig recalled.
“That’s what we’ve done ever since.”
By DENISE GRADY
Published: September 12, 2011
PHILADELPHIA — A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose.
Doctors removed a billion of his T-cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins.
At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst.
A few weeks later, the fevers were gone. And so was the leukemia.
There was no trace of it anywhere — no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells.
A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work.
“I have my life back,” he said.
Mr. Ludwig’s doctors have not claimed that he is cured — it is too soon to tell — nor have they declared victory over leukemia on the basis of this experiment, which involved only three patients. The research, they say, has far to go; the treatment is still experimental, not available outside of studies.
But scientists say the treatment that helped Mr. Ludwig, described recently in The New England Journal of Medicine and Science Translational Medicine, may signify a turning point in the long struggle to develop effective gene therapies against cancer. And not just for leukemia patients: other cancers may also be vulnerable to this novel approach — which employs a disabled form of H.I.V.-1, the virus that causes AIDS, to carry cancer-fighting genes into the patients’ T-cells. In essence, the team is using gene therapy to accomplish something that researchers have hoped to do for decades: train a person’s own immune system to kill cancer cells.
Two other patients have undergone the experimental treatment. One had a partial remission: his disease lessened but did not go away completely. Another had a complete remission. All three had had advanced chronic lymphocytic leukemia and had run out of chemotherapy options. Usually, the only hope for a remission in such cases is a bone-marrow transplant, but these patients were not candidates for it.
Dr. Carl June, who led the research and directs translational medicine in the Abramson Cancer Center at the University of Pennsylvania, said that the results stunned even him and his colleagues, Dr. David L. Porter, Bruce Levine and Michael Kalos. They had hoped to see some benefit but had not dared dream of complete, prolonged remissions. Indeed, when Mr. Ludwig began running fevers, the doctors did not realize at first that it was a sign that his T-cells were engaged in a furious battle with his cancer.
Other experts in the field said the results were a major advance.
“It’s great work,” said Dr. Walter J. Urba of the Providence Cancer Center and Earle A. Chiles Research Institute in Portland, Ore. He called the patients’ recoveries remarkable, exciting and significant. “I feel very positive about this new technology. Conceptually, it’s very, very big.”
Dr. Urba said he thought the approach would ultimately be used against other types of cancer as well as leukemia and lymphoma. But he cautioned, “For patients today, we’re not there yet.” And he added the usual scientific caveat: To be considered valid, the results must be repeated in more patients, and by other research teams.
Dr. June called the techniques “a harvest of the information from the molecular biology revolution over the past two decades.”
Hitting a Genetic Jackpot
To make T-cells search out and destroy cancer, researchers must equip them to do several tasks: recognize the cancer, attack it, multiply, and live on inside the patient. A number of research groups have been trying to do this, but the T-cells they engineered could not accomplish all the tasks. As a result, the cells’ ability to fight tumors has generally been temporary.
The University of Pennsylvania team seems to have hit all the targets at once. Inside the patients, the T-cells modified by the researchers multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer and then gradually diminished, leaving a population of “memory” cells that can quickly proliferate again if needed.
The researchers said they were not sure which parts of their strategy made it work — special cell-culturing techniques, the use of H.I.V.-1 to carry new genes into the T-cells, or the particular pieces of DNA that they selected to reprogram the T-cells.
The concept of doctoring T-cells genetically was first developed in the 1980s by Dr. Zelig Eshhar at the Weizmann Institute of Science in Rehovot, Israel. It involves adding gene sequences from different sources to enable the T-cells to produce what researchers call chimeric antigen receptors, or CARs — protein complexes that transform the cells into, in Dr. June’s words, “serial killers.”
Mr. Ludwig’s disease, chronic lymphocytic leukemia is a cancer of B-cells, the part of the immune system that normally produces antibodies to fight infection. All B-cells, whether healthy or leukemic, have on their surfaces a protein called CD19. To treat patients with the disease, the researchers hoped to reprogram their T-cells to find CD19 and attack B-cells carrying it.
But which gene sequences should be used to reprogram the T-cells, from which sources? And how do you insert them?
Various research groups have used different methods. Viruses are often used as carriers (or vectors) to insert DNA into other cells because that kind of genetic sabotage is exactly what viruses normally specialize in doing. To modify their patients’ T-cells, Dr. June and his colleagues tried a daring approach: they used a disabled form of H.I.V.-1. They are the first ever to use H.I.V.-1 as the vector in gene therapy for cancer patients (the virus has been used in other diseases).
The AIDS virus is a natural for this kind of treatment, Dr. June said, because it evolved to invade T-cells. The idea of putting any form of the AIDS virus into people sounds a bit frightening, he acknowledged, but the virus used by his team was “gutted” and was no longer harmful. Other researchers had altered and disabled the virus by adding DNA from humans, mice and cows, and from a virus that infects woodchucks and another that infects cows. Each bit was chosen for a particular trait, all pieced together into a vector that Dr. June called a “Rube Goldberg-like solution” and “truly a zoo.”
“It incorporates the ability of H.I.V. to infect cells but not to reproduce itself,” he said.
To administer the treatment, the researchers collected as many of the patients’ T-cells as they could by passing their blood through a machine that removed the cells and returned the other blood components back into the patients’ veins. The T-cells were exposed to the vector, which transformed them genetically, and then were frozen. Meanwhile, the patients were given chemotherapy to deplete any remaining T-cells, because the native T-cells might impede the growth of the altered ones. Finally, the T-cells were infused back into the patients.
Then, Dr. June said, “The patient becomes a bioreactor” as the T-cells proliferate, pouring out chemicals called cytokines that cause fever, chills, fatigue and other flulike symptoms.
The treatment wiped out all of the patients’ B-cells, both healthy ones and leukemic ones, and will continue to do for as long as the new T-cells persist in the body, which could be forever (and ideally should be, to keep the leukemia at bay). The lack of B-cells means that the patients may be left vulnerable to infection, and they will need periodic infusions of a substance called intravenous immune globulin to protect them.
So far, the lack of B-cells has not caused problems for Mr. Ludwig. He receives the infusions every few months. He had been receiving them even before the experimental treatment because the leukemia had already knocked out his healthy B-cells.
One thing that is not clear is why Patient 1 and Patient 3 had complete remissions, and Patient 2 did not. The researchers said that when Patient 2 developed chills and fever, he was treated with steroids at another hospital, and the drugs may have halted the T-cells’ activity. But they cannot be sure. It may also be that his disease was too severe.
The researchers wrote an entire scientific article about Patient 3, which was published in The New England Journal of Medicine. Like the other patients, he also ran fevers and felt ill, but the reaction took longer to set in, and he also developed kidney and liver trouble — a sign of tumor lysis syndrome, a condition that occurs when large numbers of cancer cells die off and dump their contents, which can clog the kidneys. He was given drugs to prevent kidney damage. He had a complete remission.
What the journal article did not mention was that Patient 3 was almost not treated.
Because of his illness and some production problems, the researchers said, they could not produce anywhere near as many altered T-cells for him as they had for the other two patients — only 14 million (“a mouse dose,” Dr. Porter said), versus 1 billion for Mr. Ludwig and 580 million for Patient 2. After debate, they decided to treat him anyway.
Patient 3 declined to be interviewed, but he wrote anonymously about his experience for the University of Pennsylvania Web site. When he developed chills and a fever, he said, “I was sure the war was on — I was sure C.L.L. cells were dying.”
He wrote that he was a scientist, and that when he was young had dreamed of someday making a discovery that would benefit mankind. But, he concluded, “I never imagined I would be part of the experiment.”
When he told Patient 3 that he was remission, Dr. Porter said, they both had tears in their eyes.
Not Without Danger to Patients
While promising, the new techniques developed by the University of Pennsylvania researchers are not without danger to patients. Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.
She developed severe breathing trouble 15 minutes after receiving the T-cells, had to be put on a ventilator and died a few days later. Apparently, a protein target on the cancer cells was also present in her lungs, and the T-cells homed in on it.
Researchers at Memorial Sloan Kettering Cancer in New York also reported a death last year in a T-cell trial for leukemia (also published in Molecular Therapy). An autopsy found that the patient had apparently died from sepsis, not from the T-cells, but because he died just four days after the infusion, the researchers said they considered the treatment a possible factor.
Dr. June said his team hopes to use T-cells against solid tumors, including some that are very hard to treat, like mesothelioma and ovarian and pancreatic cancer. But possible adverse reactions are a real concern, he said, noting that one of the protein targets on the tumor cells is also found on membranes that line the chest and abdomen. T-cell attacks could cause serious inflammation in those membranes and mimic lupus, a serious autoimmune disease.
Even if the T-cells do not hit innocent targets, there are still risks. Proteins they release could cause a “cytokine storm”— high fevers, swelling, inflammation and dangerously low blood pressure — which can be fatal. Or, if the treatment rapidly kills billions of cancer cells, the debris can damage the kidney and cause other problems.
Even if the new T-cell treatment proves to work, the drug industry will be needed to mass produce it. But Dr. June said the research is being done only at universities, not at drug companies. For the drug industry to take interest, he said, there will have to be overwhelming proof that the treatment is far better than existing ones.
“Then I think they’ll jump into it,” he said. “My challenge now is to do this in a larger set of patients with randomization, and to show that we have the same effects.”
Mr. Ludwig said that when entered the trial, he had no options left. Indeed, Dr. June said that Mr. Ludwig was “almost dead” from the leukemia, and the effort to treat him was a “Hail Mary.”
Mr. Ludwig said: “I don’t recall anybody saying there was going to be a remission. I don’t think they were dreaming to that extent.”
The trial was a Phase 1 study, meaning that its main goal was to find out whether the treatment was safe, and at what dose. Of course, doctors and patients always hope that there will be some benefit, but that was not an official endpoint.
Mr. Ludwig thought that if the trial could buy him six months or a year, it would be worth the gamble. But even if the study did not help him, he felt it would still be worthwhile if he could help the study.
When the fevers hit, he had no idea that might be a good sign. Instead, he assumed the treatment was not working. But a few weeks later, he said that his oncologist, Dr. Alison Loren, told him, “We can’t find any cancer in your bone marrow.”
Remembering the moment, Mr. Ludwig paused and said, “I got goose bumps just telling you those words.”
“I feel wonderful,” Mr. Ludwig said during a recent interview. “I walked 18 holes on the golf course this morning.”
Before the study, he was weak, suffered repeated bouts of pneumonia and was wasting away. Now, he is full of energy. He has gained 40 pounds. He and his wife bought an R.V., in which they travel with their grandson and nephew. “I feel normal, like I did 10 years before I was diagnosed,” Mr. Ludwig said. “This clinical trial saved my life.”
Dr. Loren said in an interview, “I hate to say it in that dramatic way, but I do think it saved his life.”
Mr. Ludwig said that Dr. Loren told him and his wife something he considered profound. “She said, ‘We don’t know how long it’s going to last. Enjoy every day,’ ” Mr. Ludwig recalled.
“That’s what we’ve done ever since.”
Tuesday, September 13, 2011
Tuesday, September 6, 2011
Disabled Patients Mind-Meld With Robots
http://news.sciencemag.org/sciencenow/2011/09/disabled-patients-mind-meld-with.html
By Sara Reardon on 6 September 2011, 1:17 PM | 0 Comments
Credit: José del R. Millán
They're not quite psychic yet, but machines are getting better at reading your mind. Researchers have invented a new, noninvasive method for recording patterns of brain activity and using them to steer a robot. Scientists hope the technology will give "locked in" patients—those too disabled to communicate with the outside world—the ability to interact with others and even give the illusion of being physically present, or "telepresent," with friends and family.
Previous brain-machine interface systems have made it possible for people to control robots, cursors, or prosthetics with conscious thought, but they often take a lot of effort and concentration, says José del R. Millán, a biomedical engineer at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, who develops brain-machine interface systems that don't need to be implanted into the brain. Millán's goal is to make control as easy as driving a car on a highway. A partially autonomous robot would allow a user to stop concentrating on tasks that he or she would normally do subconsciously, such as following a person or avoiding running into walls. But if the robot encounters an unexpected event and needs to make a split-second decision, the user's thoughts can override the robot's artificial intelligence.
To test their technology, Millán and colleagues created a telepresent robot by modifying a commercially available bot called Robotino. The robot looks a bit like a platform on three wheels, and it can avoid obstacles on its own using infrared sensors. On top of the robot, the researchers placed a laptop running Skype, a voice and video Internet chat system, over a wireless Internet connection. This allowed the human controller to see where the robot was going, and, because the laptop also showed a video of the user, it allowed others to interact with the user as though the user were actually there. The user also wore a cap of tiny electroencephalogram (EEG) electrodes, which measured his or her brain activity. This system translates the EEG signals into navigation instructions and transmits them in real time to the robot.
EEG patterns for movement and navigation are similar from person to person, and Millán's group has previously demonstrated that after a little practice, a healthy person can share control with the robot with very little effort. But would a bed-bound patient, who hasn't used his limbs for years, have the same pattern of brain waves and be able to control robots as effectively?
The researchers recruited two patients whose lower bodies were paralyzed and who had been bed bound for 6 or 7 years. The researchers trained the patients to control the robot for 1 hour per week for 6 weeks. With the instructions being transmitted over a wireless connection, the patients didn't need to leave the hospital and were able to control the robot in Millán's lab at EPFL, 100 kilometers away. At the end of the training period, the researchers instructed the subjects to drive the robot to various targets, such as furniture, people, and small objects, around the lab for 12 minutes.
The disabled patients performed just as well as healthy subjects, Millán and colleagues report this week at the IEEE Engineering in Medicine and Biology Society conference in Boston. When the researchers turned the shared control off, forcing the subjects to constantly concentrate on controlling the robot, the subjects took considerably longer to navigate the maze than when they shared control.
Millán says he wasn't terribly surprised that disabled people could control the robot, as previous research using brain scans has shown that even patients who have been paralyzed since birth can still imagine moving their limbs. But he was surprised how fast they learned. He is now hoping to involve more bed-bound patients, including locked-in patients in the study. He also sees future applications for the shared control brain-machine interface, such as modifying it to let a user control a prosthetic limb or a wheelchair. And the researchers may eventually add an arm to the current telepresent robot to allow it to grasp objects.
Neuroengineer José Carmena of the University of California, Berkeley, says Millán's approach "has a lot of novelty" in how it integrates both natural and artificial systems. There are some disadvantages, he says, to a system that uses a cap instead of a device implanted directly in the brain, such as the background signals that the cap might pick up. But for this application, he says, it is "an interesting avenue for telepresence."
Millán says that the bed-bound patients were thrilled to participate in the study. "This opens a new possibility for families," he says, who could interact with their bed-bound loved ones over a video connection without having to sit in front of a computer. But would the families of the disabled patients be creeped out by a robot following them around in the kitchen while they make dinner? "Well, that's something we'll have to ask," he says.
By Sara Reardon on 6 September 2011, 1:17 PM | 0 Comments
Credit: José del R. Millán
They're not quite psychic yet, but machines are getting better at reading your mind. Researchers have invented a new, noninvasive method for recording patterns of brain activity and using them to steer a robot. Scientists hope the technology will give "locked in" patients—those too disabled to communicate with the outside world—the ability to interact with others and even give the illusion of being physically present, or "telepresent," with friends and family.
Previous brain-machine interface systems have made it possible for people to control robots, cursors, or prosthetics with conscious thought, but they often take a lot of effort and concentration, says José del R. Millán, a biomedical engineer at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, who develops brain-machine interface systems that don't need to be implanted into the brain. Millán's goal is to make control as easy as driving a car on a highway. A partially autonomous robot would allow a user to stop concentrating on tasks that he or she would normally do subconsciously, such as following a person or avoiding running into walls. But if the robot encounters an unexpected event and needs to make a split-second decision, the user's thoughts can override the robot's artificial intelligence.
To test their technology, Millán and colleagues created a telepresent robot by modifying a commercially available bot called Robotino. The robot looks a bit like a platform on three wheels, and it can avoid obstacles on its own using infrared sensors. On top of the robot, the researchers placed a laptop running Skype, a voice and video Internet chat system, over a wireless Internet connection. This allowed the human controller to see where the robot was going, and, because the laptop also showed a video of the user, it allowed others to interact with the user as though the user were actually there. The user also wore a cap of tiny electroencephalogram (EEG) electrodes, which measured his or her brain activity. This system translates the EEG signals into navigation instructions and transmits them in real time to the robot.
EEG patterns for movement and navigation are similar from person to person, and Millán's group has previously demonstrated that after a little practice, a healthy person can share control with the robot with very little effort. But would a bed-bound patient, who hasn't used his limbs for years, have the same pattern of brain waves and be able to control robots as effectively?
The researchers recruited two patients whose lower bodies were paralyzed and who had been bed bound for 6 or 7 years. The researchers trained the patients to control the robot for 1 hour per week for 6 weeks. With the instructions being transmitted over a wireless connection, the patients didn't need to leave the hospital and were able to control the robot in Millán's lab at EPFL, 100 kilometers away. At the end of the training period, the researchers instructed the subjects to drive the robot to various targets, such as furniture, people, and small objects, around the lab for 12 minutes.
The disabled patients performed just as well as healthy subjects, Millán and colleagues report this week at the IEEE Engineering in Medicine and Biology Society conference in Boston. When the researchers turned the shared control off, forcing the subjects to constantly concentrate on controlling the robot, the subjects took considerably longer to navigate the maze than when they shared control.
Millán says he wasn't terribly surprised that disabled people could control the robot, as previous research using brain scans has shown that even patients who have been paralyzed since birth can still imagine moving their limbs. But he was surprised how fast they learned. He is now hoping to involve more bed-bound patients, including locked-in patients in the study. He also sees future applications for the shared control brain-machine interface, such as modifying it to let a user control a prosthetic limb or a wheelchair. And the researchers may eventually add an arm to the current telepresent robot to allow it to grasp objects.
Neuroengineer José Carmena of the University of California, Berkeley, says Millán's approach "has a lot of novelty" in how it integrates both natural and artificial systems. There are some disadvantages, he says, to a system that uses a cap instead of a device implanted directly in the brain, such as the background signals that the cap might pick up. But for this application, he says, it is "an interesting avenue for telepresence."
Millán says that the bed-bound patients were thrilled to participate in the study. "This opens a new possibility for families," he says, who could interact with their bed-bound loved ones over a video connection without having to sit in front of a computer. But would the families of the disabled patients be creeped out by a robot following them around in the kitchen while they make dinner? "Well, that's something we'll have to ask," he says.
Plastic shelves idea submission
***
After contacting their customer service with a written description, they asked for clarification, so I submitted a rough mockup - they replied with an invitation to sign a letter of understanding and submit to their marketing dept.
Mockup submitted to their marketing dept with the following description:
...plastic inserts could serve to enclose any side of each shelf so that one might use the shelving as a bookcase or as a container - perfect for students who don't want to deal with assembling wooden shelves which are heavy and expensive.
The slots in the diagram are probably too thick - the diagram is not exact, rather a simplified representation of adding plastic inserts via slots added to the boundaries of the shelving tiers, thereby allowing the shelves to be enclosed for the functionality of acting as bookshelves, as an enclosed container, etc. A thin insert will serve the purpose and maximize the available surface real estate.
I put your shelves into the closets of my office so the walls of the closet offer enclosure and serve as bookshelves.
The reason I love your shelves is that they are strong, lightweight and flexible - I have one tier left over with 4 legs and I use it in the office as a table top which can be broken down easily. They are like Legos - I can make them as tall or as low as I need.
After contacting their customer service with a written description, they asked for clarification, so I submitted a rough mockup - they replied with an invitation to sign a letter of understanding and submit to their marketing dept.
Mockup submitted to their marketing dept with the following description:
...plastic inserts could serve to enclose any side of each shelf so that one might use the shelving as a bookcase or as a container - perfect for students who don't want to deal with assembling wooden shelves which are heavy and expensive.
The slots in the diagram are probably too thick - the diagram is not exact, rather a simplified representation of adding plastic inserts via slots added to the boundaries of the shelving tiers, thereby allowing the shelves to be enclosed for the functionality of acting as bookshelves, as an enclosed container, etc. A thin insert will serve the purpose and maximize the available surface real estate.
I put your shelves into the closets of my office so the walls of the closet offer enclosure and serve as bookshelves.
The reason I love your shelves is that they are strong, lightweight and flexible - I have one tier left over with 4 legs and I use it in the office as a table top which can be broken down easily. They are like Legos - I can make them as tall or as low as I need.
Monday, September 5, 2011
Malaysia development
http://news.bbc.co.uk/2/hi/programmes/fast_track/9575962.stm
By 2025 Malaysia will have a brand new metropolis of three million people. But will tourists be tempted by what Iskandar has to offer?
Several flagship projects are under construction, including luxury hotels, shopping centres and theme parks - all aimed at increasing investment in Malaysia.
http://en.wikipedia.org/wiki/Iskandar_Malaysia
The Maldives meets Dubai, in Malaysia
http://www.bbc.com/travel/feature/20110901-the-maldives-meets-dubai-in-malaysia
02 September 2011 | By Carmen Roberts
Golden Palm Tree Resort and Spa, off the coast of Selangor in Malaysia. (Sepang Goldcoast)
The water gently laps beneath the deck of our villa, as we admire the sun setting over the Straits of Malacca. Condensation streams down the side of my glass of iced kalamansi juice as we gaze at the ships on the distant horizon. The only sound is the squawk of a native bird flying overhead.
This is the Golden Palm Tree Resort and Spa, a luxurious Maldivian-style, over-water villa complex, just off the coast of Selangor in Malaysia. It is hard to believe that only a few years ago, this was the humble, sleepy fishing village of Bagan Lalang, in Sepang. It has since been transformed into part of a glittering, 22km-long coastline development, poised to place Malaysia firmly on the world’s luxury property and tourism map.
Sepang Goldcoast was conceptualised as an integrated holiday destination catering to international tourists and travellers, modelled on famous beach havens such as the Gold Coast in Queensland, Australia and Miami Beach in the United States.
Sepang is situated in Malaysia’s richest and most developed state, Selangor, which is often referred to as the gateway to Malaysia; Port Klang, the country’s largest port, and the Kuala Lumpur International Airport are both located there.
Surrounding the Federal Territories of Kuala Lumpur and Putrajaya, Selangor's strategic location boosts its appeal as the preferred holiday destination for the rising middle class Malaysians and foreign tourists. Sepang Goldcoast is a mere 30-minute drive from the airport and just over an hour from the capital.
Local attractions include the stone-carved Hindu temples in the Batu Caves, the aboriginal communities at Pulau Carey and international sporting events like Formula One and yacht races. But the standout attraction at the moment is the Gold Palm Tree Resort and Spa, which opened last summer.
From the air, close to 400 villas fan out into the ocean in the shape of a giant palm tree, much like the Palm in Dubai -- a grandiose development that has been plagued with problems from its inception. Malaysian Tourism officials are counting on the bold resort development to be the jewel in their tourism crown rather than an international embarrassment.
Rooms start a RM800, a reasonable rate compared to similar over-water villas in destinations like the Maldives. When completed, sometime over the next decade, Sepang Goldcoast will have resorts, amusement parks, a marina, floating market and wildlife habitats. Besides sun worshiping, planned local activities include surfing, canoeing, kayaking canopy walks and yoga.
While a waterfront renaissance is nothing new, Malaysia is now realising the opportunities in drawing investments and creating iconic global attractions like this one. Hopefully Sepang Goldcoast will be an example of how revitalising rivers and waterways along with building tourist infrastructure, can reap economic rewards.
By 2025 Malaysia will have a brand new metropolis of three million people. But will tourists be tempted by what Iskandar has to offer?
Several flagship projects are under construction, including luxury hotels, shopping centres and theme parks - all aimed at increasing investment in Malaysia.
http://en.wikipedia.org/wiki/Iskandar_Malaysia
The Maldives meets Dubai, in Malaysia
http://www.bbc.com/travel/feature/20110901-the-maldives-meets-dubai-in-malaysia
02 September 2011 | By Carmen Roberts
Golden Palm Tree Resort and Spa, off the coast of Selangor in Malaysia. (Sepang Goldcoast)
The water gently laps beneath the deck of our villa, as we admire the sun setting over the Straits of Malacca. Condensation streams down the side of my glass of iced kalamansi juice as we gaze at the ships on the distant horizon. The only sound is the squawk of a native bird flying overhead.
This is the Golden Palm Tree Resort and Spa, a luxurious Maldivian-style, over-water villa complex, just off the coast of Selangor in Malaysia. It is hard to believe that only a few years ago, this was the humble, sleepy fishing village of Bagan Lalang, in Sepang. It has since been transformed into part of a glittering, 22km-long coastline development, poised to place Malaysia firmly on the world’s luxury property and tourism map.
Sepang Goldcoast was conceptualised as an integrated holiday destination catering to international tourists and travellers, modelled on famous beach havens such as the Gold Coast in Queensland, Australia and Miami Beach in the United States.
Sepang is situated in Malaysia’s richest and most developed state, Selangor, which is often referred to as the gateway to Malaysia; Port Klang, the country’s largest port, and the Kuala Lumpur International Airport are both located there.
Surrounding the Federal Territories of Kuala Lumpur and Putrajaya, Selangor's strategic location boosts its appeal as the preferred holiday destination for the rising middle class Malaysians and foreign tourists. Sepang Goldcoast is a mere 30-minute drive from the airport and just over an hour from the capital.
Local attractions include the stone-carved Hindu temples in the Batu Caves, the aboriginal communities at Pulau Carey and international sporting events like Formula One and yacht races. But the standout attraction at the moment is the Gold Palm Tree Resort and Spa, which opened last summer.
From the air, close to 400 villas fan out into the ocean in the shape of a giant palm tree, much like the Palm in Dubai -- a grandiose development that has been plagued with problems from its inception. Malaysian Tourism officials are counting on the bold resort development to be the jewel in their tourism crown rather than an international embarrassment.
Rooms start a RM800, a reasonable rate compared to similar over-water villas in destinations like the Maldives. When completed, sometime over the next decade, Sepang Goldcoast will have resorts, amusement parks, a marina, floating market and wildlife habitats. Besides sun worshiping, planned local activities include surfing, canoeing, kayaking canopy walks and yoga.
While a waterfront renaissance is nothing new, Malaysia is now realising the opportunities in drawing investments and creating iconic global attractions like this one. Hopefully Sepang Goldcoast will be an example of how revitalising rivers and waterways along with building tourist infrastructure, can reap economic rewards.
Friday, September 2, 2011
The man who draws in his sleep
http://theweek.com/article/index/218769/the-man-who-draws-in-his-sleep
The man who draws in his sleep
What makes a man get out of bed and start drawing — while he's still asleep? Doctors are baffled; art critics are impressed
posted on September 1, 2011, at 7:00 AM
Lee Hadwin is only a decent artist when he's awake, but asleep he's created masterpieces that have reportedly sold for six figures.
Lee Hadwin is only a decent artist when he's awake, but asleep he's created masterpieces that have reportedly sold for six figures. Photo: YouTube
Best Opinion: Huff. Post, Whitchurch Arts
The video: Lee Hadwin appears to be a perfectly normal 37-year-old nurse — by day. But when night falls, his other persona takes over: Hadwin is a gifted artist who sketches and paints in his sleep. (Watch the video, below.) While there are countless documented cases of sleep-walking, this is the first known case of sleep-drawing. Hadwin got started at age 4, when he scribbled on walls and furniture. Now some of his pieces fetch six-figure prices. Still, the North Wales native doesn't want to make art his career. He never studied art, and is lousy at drawing when awake. "Art has never interested me at all," says Hadwin, as quoted by the BBC. But just in case, he now prepares by leaving a sketchpad, brushes, and other art supplies in his bedroom.
The reaction: "The whole thing is almost surreal," says Dean Praetorius at The Huffington Post. "It's almost scary how good he is, too." Hadwin says that an evening of drinking can often trigger an episode of sleep-drawing. His condition leaves experts baffled: Doctors at the Edinburgh Sleep Center can't even determine what stage of sleep Hadwin is in when his creative impulses kick in. Whatever is happening here, says Whitchurch Arts, it's working. And — who knows — there could be more sleep-drawing prodigies out there. "Perhaps put out a piece of paper and pencil on the bedside table tonight to find out."
The man who draws in his sleep
What makes a man get out of bed and start drawing — while he's still asleep? Doctors are baffled; art critics are impressed
posted on September 1, 2011, at 7:00 AM
Lee Hadwin is only a decent artist when he's awake, but asleep he's created masterpieces that have reportedly sold for six figures.
Lee Hadwin is only a decent artist when he's awake, but asleep he's created masterpieces that have reportedly sold for six figures. Photo: YouTube
Best Opinion: Huff. Post, Whitchurch Arts
The video: Lee Hadwin appears to be a perfectly normal 37-year-old nurse — by day. But when night falls, his other persona takes over: Hadwin is a gifted artist who sketches and paints in his sleep. (Watch the video, below.) While there are countless documented cases of sleep-walking, this is the first known case of sleep-drawing. Hadwin got started at age 4, when he scribbled on walls and furniture. Now some of his pieces fetch six-figure prices. Still, the North Wales native doesn't want to make art his career. He never studied art, and is lousy at drawing when awake. "Art has never interested me at all," says Hadwin, as quoted by the BBC. But just in case, he now prepares by leaving a sketchpad, brushes, and other art supplies in his bedroom.
The reaction: "The whole thing is almost surreal," says Dean Praetorius at The Huffington Post. "It's almost scary how good he is, too." Hadwin says that an evening of drinking can often trigger an episode of sleep-drawing. His condition leaves experts baffled: Doctors at the Edinburgh Sleep Center can't even determine what stage of sleep Hadwin is in when his creative impulses kick in. Whatever is happening here, says Whitchurch Arts, it's working. And — who knows — there could be more sleep-drawing prodigies out there. "Perhaps put out a piece of paper and pencil on the bedside table tonight to find out."
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