Cancer drugs may hold key to treating Down syndrome

 

Wed, 05/20/2015 - 7:51am Ian Demsky, University of Michigan A class of FDA-approved cancer drugs may be able to prevent problems with brain cell development associated with disorders including Down syndrome and Fragile X syndrome, researchers at the University of Michigan Life Sciences Institute have found. The researchers' proof-of-concept study using fruit fly models of brain dysfunction was published in eLife. They show that giving the leukemia drugs nilotinib or bafetinib to fly larvae with the equivalent of Fragile X prevented the wild overgrowth of neuron endings associated with the disorder. Meanwhile, the drugs—both tyrosine-kinase inhibitors—did not adversely affect the development or neuronal growth in healthy flies. "This study proposes a potential therapeutic approach for treating brain disorders associated with dysregulated expression of the Dscam protein, which is seen in both Down syndrome and Fragile X syndrome," said senior study author Bing Ye, whose lab is in the LSI. Graduate student Gabriella Sterne and postdoctoral fellow Jung Hwan Kim are co-first authors of the paper. Down syndrome and Fragile X are the two most prevalent genetic causes of intellectual disabilities. Down syndrome is caused by an extra copy of chromosome 21, while Fragile X is caused by a mutation in a single gene. Recent studies by the Ye lab and by researchers at other institutions have pointed to a possible link between the two conditions. During early development, neurons produce high levels of the proteins encoded by a gene called DSCAM as they undergo an intense period of extending and branching to connect with other neurons. (DSCAM stands for Down Syndrome Cell-Adhesion Molecule.) But problems can occur when Dscam levels don't go back down. In flies, when Dscam levels stay high, branches off of the ends of their neurons grow too long and make faulty connections with neighboring neurons. In humans, whose nervous systems and brains are far more complicated, the downstream impacts of Dscam dysregulation have not been fully identified. In a series of experiments outlined in the study, the researchers showed that the Dscam protein activates another protein known as Abelson tyrosine kinase (Abl). The scientists then took genetically modified flies that produced high levels of Dscam and gave them the cancer drug, which acts by blocking the action of Abl. In one experiment, directly overexpressing Dscam led to flies with neuron endings (called presynaptic terminals) more than 50% longer than normal. But flies treated with the cancer drug showed only a 15% increase. In another experiment using a genetic model of Fragile X, the flies had presynaptic terminals almost a third longer than normal, but those that received the drug saw only 3% more terminal growth than the control group. "Although there's an amazing amount of similarity between flies and humans, more study is needed before we'll know if this could be a safe and effective treatment for human patients," said Ye, who is also an assistant professor in the Dept. of Cell and Developmental Biology at the U-M Medical School. The next step would be to test the approach in mouse models of these brain disorders. Collaborations with oncologists and pharmaceutical companies will also be essential to ensure Abl inhibitors are safe to use in this context, Ye said. "This study is also an example of the utility of model organisms," Ye said. "Fruit flies grow and develop rapidly—and although the behaviors of flies and humans are very different, our neurons grow in much the same way, and the genes controlling this process are usually the same or very similar." Source: University. of Michigan

Solar-powered Safari lodge in Africa

 

Les architectes Michaelis Boyd et Nick Plewman ont imaginé un véritable cocon luxueux au coeur de Botswana. Les amateurs de Safari peuvent séjourner au Sandibe Okavango Safari Lodge : une habitation uniquement alimentée par l’énergie solaire, faisant entièrement corps avec la nature de par sa structure circulaire faite de bois et de couleurs chauds.

Sennheiser takes a closed in approach to audiophile quality

 

Sennheiser's first closed-back audiophile headphones, the HD 630VB Image Gallery (3 images) Though open high definition headphones like Sennheiser's wonderful HD 598s or the mighty HD 800s can offer greater spacing and a more natural airy feel than closed-back designs, they can't really be used in anything but the quietest of environments so listening on the move is simply not an option. The German audio brand says that it's new HD 630VB headphones offer hi-res music lovers a balanced, airy and audiophile-grade listening experience with the benefit of effective passive noise isolation. Introduced last week at the High End Show in Munich, Germany, the HD 630VB circumaural headphones feature a new proprietary high performance transducer that provides the power for high resolution music file listening with "an impressively spatial sound image." Aluminum coil wire, combined with a reported total harmonic distortion of less than 0.08 percent (at 1 kHz and 100 dB SPL), promises precise, unaltered sonic reproduction across a large frequency range of 10 Hz to 42 kHz. Though if your tastes run to more bass-heavy listening, Sennheiser has also included a rotary dial to tweak the amount of thunder coming through the drivers. Playback and volume levels can be controlled via the right ear cup, too, and users can take calls with the help of an omnidirectional microphone integrated into the oxygen-free cable. Robust and classy aluminum ear cups, headband and sliders contribute to a scale-tipping weight of just 400 g (14 oz), the HD 630VBs can be collapsed down for travel and a 23 ohm impedance makes them mobile music device-friendly. Sennheiser's first closed-back audiophile headphones are due for release next month for US$549.95. Product page: Sennheiser HD 630VB

Vortex bladeless turbines wobble to generate energy

 

Groups of Vortex units can be placed close together as the disruption of the wind stream is not as critical to operation as it is for traditional, blade-driven wind turbines (Credit: Vortex) Image Gallery (4 images) Looking somewhat like a giant reed gently swaying in the wind, the new Vortex bladeless wind-driven generator prototype produces electricity with very few moving parts, on a very small footprint, and in almost complete silence. Designed to reduce the visual and aural impact of traditional spinning-blade turbines, this new device takes advantage of the power contained in swirling vortices of air. Many opponents of spinning wind turbines point to their supposed danger to birds and other flying animals, as well as their rather noisy operation and – particularly in commercial installations – their enormous size. Though these may well be excuses by those who prefer to stay with older electricity generating technologies that they know and trust, standard wind-driven turbines do have these issues and this tends to hold back their universal acceptance and use. This is where the creators of the Vortex bladeless believe that their device has the advantage. A relatively compact unit, it relies on the oscillation of its reed-like mast in reaction to air vortices to move a series of magnets located in the joint near its base to generate electricity. Though obviously not as efficient as a high-speed, directly wind-driven turbine, this is offset by the fact that the Vortex has fewer moving parts and is, according to the creators, up to 80 percent more cost effective to maintain. Coupled to the notion that it supposedly has a greater than 50 percent manufacturing cost advantage and a 40 percent reduction in its carbon footprint compared to standard wind turbines, the system also seems to offer direct economic advantages. We've explored a number of bladeless wind-turbines before – the Solar Aero turbine being one (though, by definition, not really bladeless as it merely covered the spinning blades with a housing) and the Saphonian being another. The latter being more of a true bladeless "turbine," it still required hydraulic actuation of pistons to generate electricity, so its efficiency was probably not all that great (and, to be perfectly frank, it was not strictly a turbine either as it had no spinning parts). The Vortex, on the other hand, is purported to take advantage of the swirling motion of wind and not direct force like the aforementioned units. This means that it can generate energy from the repeating pattern of vortices (known as the Kármán vortex street), which are generated as the air separates to pass by a blunt body, such as the Vortex structure itself. This also means that groups of Vortex units can be huddled closer together as the disruption of air movement in the wind stream is nowhere near as critical as it is when positioning standard, blade-driven wind turbines. This will also help ameliorate the inherent efficiencies in each unit as they can be grouped much closer together than their standard turbine counterparts and, therefore, potentially generate more power per square meter. The first model to be made available commercially will be known as the Mini: a 4 kW, 12.5 meter (41 ft) high unit intended for residential and small-scale commercial application. A larger model, dubbed the Gran, is also being designed and is a unit with a greater than one-megawatt output intended for use in large-scale power generation for industry and electricity companies. To get their creations to production, the team at Vortex will be launching a crowdfunding campaign on June 1, with details to become available via email alerts on the company's website.   Source: Vortex

14 Totally Free Things On The Internet Everyone Should Be Taking Advantage Of

 

Signifyd The wunderkinds over on Reddit recently took a break from uncracked safes and banana-based measurements to post a mega-thread addressing the best of the best of all things free on the interwebs, and I couldn't help but share some of the highlights with you all. If you're savvy, you might recognize a few of these bad boys already, but don't spoil the Supermarket Sweep-style fun for the rest of us, OK? ii.library.jhu.edu 1. College courses, no tuition Is the fear of smothering, unbearable student debt steering you away from the path of higher education? Class Central exposes hundreds of online class courses from the likes of Harvard, Stanford, and MIT, without that pesky tuition nonsense. This means you can educate yourself in subjects like Molecular Biology, Advanced Operating Systems, or The Rise Of Superheroes And Their Impact On Pop Culture. It's all the information you need to become a fully functional adult in today's global economy, without the loans, leftover futons, and career-debilitating Facebook photo rolls. related 33 Things You Used To Own That Your iPhone Replaced Wikimedia 2. Self-destructing email addresses With 10 Minute Mail, you can create an extremely temporary email address that will automatically self-destruct in 10 minutes, allowing you to sign up for sites, lists, and deals without the unbearable spam cannon that normally accompanies your quiet compliance. Also good for anonymous threats and insults to friends/family members. Not that I'd do that, of course. imagenesygraficos 3. Ambient sounds for any occasion If you simply can't work/sleep/make love without some kind of comforting white noise cascading over your eardrums, A Soft Murmur has you covered with all the classic ambient noises, and the somewhat odd ability to play a bunch of them at once. DJ Careless Whisper? You had me at "singing bowl" and "fire." related Why I Will Never Wear the Apple Watch Wikimedia 4. Learn every language on Earth If you've ever felt devastatingly isolated at your Swedish cousin's wedding to her Argentinean lover in Seoul (due to the triple language barrier), Duolingo might be right for you. Touted as the free Rosetta Stone—and some consider it to be even better—Duolingo softens the blow of learning another language by taking the pressure off your wallet. You'll be ordering with cultural authenticity at Taco Bell en un santiamén, muchacho. The Filmmakers Workshop 5. Unlimited access to a mega-library of documentaries Documentaries have been experiencing a recent boom thanks to their accessibility on Netflix, but one can only watch Jiro Dreams of Sushi so many times, and there's no chance in hell I'm buying a DVD again. With Documentary Heaven you have access to an endless river of reality piping through your computer monitor, like trout swimming upstream during their annual mating season (watch the documentary, you'll see what I mean). The Movie Mash 6. Someone to spill your guts to Everyone needs somebody, sometime—as Dean Martin once famously crooned, and most of the time, you don't have the funds or time to drop on a therapist or high-end escort. Welcome to 7 Cups of Tea, a completely free way to connect live with a "listener," with a bounty of free counseling options available. It's all anonymous too, so you don't have to worry about any of your dirty little secrets becoming public. What an age to be alive. related 10 Failed Gadgets That Were Before Their Time 7. Automatic alerts or actions for everything you care about While it's been notorious on the Internet for quite some time, If This, Then That is one of those sites that's bound to blow up one day (in a good way). Once you log in, you can create a "recipe," programming an alert or action that will happen anytime two correlating actions occur on the web. For instance, you can automatically push photos posted on your Facebook to a secure Dropbox, the second they are posted. Or, have an email sent to you anytime someone mentions "Cat," "Shaving," and "Wanted by Authorities" on all your local news sites. The possibilities are endless. Craigslist 8. Free used sh*t Craigslist - the domain of questionable career opportunities as well as questionable sexual opportunities, has become a digital smorgasbord of totally free sh*t. If you select your appropriate region, you’ll see a “Free” section under the “For Sale” category (confusing, I know) chock-full to the innuendo-soaked rim with perfectly good items folks are just begging to give away. Check out what you can snag sans payment in NYC alone. Pro Tip: avoid any cloth-based furniture (for obvious, soiled reasons) as well as any intimate products, also for obvious reasons. Nintendo 9. Old-school video games For my generation, some of the best childhood memories consist of gathering around a glowing TV screen, slowing rotting our minds with video games while vehemently ignoring the shining sun and temperate climate outside. Man, those were the days. For a quick blast of nostalgia to the face, hit up this SNES, NES, and SEGA emulator to relive your pasty glory years. All you have to worry about is your boss catching you playing Castlevania in-between TPS reports. Unless you don’t have a job. Then you probably shouldn't be playing SNES emulators, anyway. related Text This Number, Get Anything You Want On-Demand Lost Type 10. All the fonts you could ever want Normally, finding the right font for your situation isn't a huge problem. But that's probably because you don't know the dizzying heights design has reached in recent years. You are in for the shock of a lifetime, pal, because Lost Type has you covered from stylized head to sans-serif toe. With psychoactive billboard sets and funkadelic superfly stylings, your eyes will be widened to the magical world of spectacular fonts, all free to use in any way you wish. But please, type responsibly. Pixlr 11. Photo editing with panache  For those who want their photos to shine a little bit brighter or to casually drop themselves into Ariana Grande’s vacation pics (no judging), but balk at the big bucks for Photoshop, the photo editing app Pixlr is available for your computer and smartphone for the low price of absolutely nothing. Though it doesn’t have the absurd level of customization and features that Photoshop so smugly touts, it's a very serviceable application for amateur to mid-level Instagrammers who are sick of using Valencia as a crutch. SavingForMyFamily 12. Piles and piles of valuable coupons This is extremely relevant for those who not only want free swag, but want their free swag to turn into other free swag. RetailMeNot is an aggregate of comped codes, coupons, and other door-busting deals for both online services and brick & mortar outfits—with offerings varying from H&M to Domino's. So, you can get those organ-constricting skinny jeans on the cheap, with money left over to get cheese-soaked, grease-stuffed sugar sticks to ensure you will never fit in them again. related The 10 Best Parts Of Pierce Brosnan's Reddit AMA 13. Manage your finances and your future Living paycheck to paycheck? Can't afford to buy milk for your nonexistent cereal? Is your life literally crashing down around you as we speak? The sleek, financial management site Mint is a payment-free resource that allows you to check your credit, pay bills, and manage your bank accounts on a safe, well-designed platform. It will pretty much handle everything that has to do with your hard-earned bacon, aside from actually earning it for you. Still waiting for that upgrade, slackers... JustGive.org 14. Help feed the world Meet the only thing on this list ideal for those instances when you are trying to actually give the world something, instead of just reaping the bounty of comped items and services like a cyber-glutton. With Freerice, you can exercise your noggin and help feed hungry humans all over the world, without sparing a dime. The site presents you with a series of questions in subjects like English grammar and basic chemistry, and for every correct answer, the World Food Programme will donate 10 grains of rice to the global cause. You can rack up the grains pretty quickly, though—and all for a worthwhile cause. It's trivia that can make an actual difference. Unlike Trivial Pursuit, which just tears families apart. Trust me, I haven't spoken to my sister in years. Denise, if you're reading this, please call me. Wil Fulton is a staff writer for Supercompressor, and he doesn't really have a sister named Denise. Though if he did, he'd probably dislike her. Follow him @WilWithOnlyOneL.

Researchers identify new target for malaria treatment

 

The breakthrough, which focuses on a membrane separating parasites from their host cells, was made when studying Toxoplasma gondii (pictured) (Credit: Centers for Disease Control and Prevention) A team of MIT researchers has discovered a new target for drug treatments for prevalent diseases such as malaria. The findings focus on a membrane between the parasite and its host cell, with scientists successfully identifying a family of proteins that, when targeted, could cut off nutrients to the parasite. Many diseases, such as malaria and tuberculosis, are caused by pathogens that exist in separate compartments within their host cells, known as parasitophorous vacuoles. The vacuole is separated from the host cytoplasm by a membrane, which protects the disease from the cell's defences. However, it also makes it difficult for the pathogen to access vital nutrients, and release the proteins necessary to spread the disease. This means that the parasite has to develop a way to get around its own barrier in order to access nutrients essential to its survival. Previous studies have revealed that the membrane is selectively permeable, but scientists have been unable to determine the molecular makeup of the pores. The MIT researchers were studying Toxoplasma, investigating how the parasite is able to release its proteins into the host cell and beyond, when they stumbled upon a discovery. They found that two proteins – GRA17 and GRA23 – were central to the process, and were of shared ancestry to proteins in the parasite Plasmodium, which were themselves responsible for a protein export system within their host cell. However, when the team stopped the proteins from functioning, the export process of parasite proteins beyond the vacuole was unchanged. Puzzled by the specific role of the proteins in the export process, the researchers added dyes to the host cell and disabled the proteins once more. Observing the cells again, they found that the proteins were no longer able to flow through the selective membrane and into the vacuole, strongly indicating that GRA17 and GRA23 are responsible for the small-molecule transfer between the host cell and the parasitophorous vacuole. Furthermore, when the team switched the export protein from the Plasmodium parasite into the Toxoplasma, the dyes were able to flow into the vacuole once more, suggesting that the family of proteins responsible for the process had indeed been successfully identified. "This very strongly suggests that you could find small-molecule drugs to target these pores, which would be very damaging to these parasites, but likely wouldn’t have any interaction with any human molecules," says research lead Dan Gold. "So I think this is a really strong potential drug target for restricting the access of these parasites to a set of nutrients." The findings were recently published in journal Cell & Microbe. Source: MIT

Panasonic's Lumix G7 boasts 4K video and photo skills

 

The Panasonic Lumix DMC-G7 is a budget-friendly 4K-shooting mirrorless camera which has inherited a number of high-end features (Credit: Panasonic) Image Gallery (6 images) Panasonic's Lumix DMC-G7 feels like it's as much a little brother to the 4K-toting GH4, as a follow-up to the G6. It's being billed as the mirrorless camera to bring the full benefits of 4K video to the rest of us, thanks to its ability to shoot 4K footage at 30 fps, and then extract 8-megapixel stills from it. While we've seen those features before, the G7 is arguably the first time they've been built into a mirrorless camera which is simultaneously powerful and accessible to the masses. The Panasonic G7 features a 16-megapixel Micro Four Thirds (17.3 x 13.0 mm) Live MOS sensor paired with an improved Venus Engine image processor to deliver high quality images in a variety of conditions. It has an extended ISO range of 100 to 25,600 and is capable of firing off bursts of full resolution images at 8 fps (frames per second) in AFS, or 6 fps in AFC when using its mechanical shutter. It can do this for around 13 frames if shooting RAW, or more than 100 if shooting JPEG files. However, while that's all well and good, it's going to be the formerly high-end 4K capabilities making their way down the Panasonic mirrorless line-up which make the G7 stand out from the crowd of mid-range mirrorless cameras on the market. First off, it can record 4K footage at a 3,840 x 2,160 resolution at 30/24 fps and 100 Mbps, along with Full HD 1080p footage at 60 fps. The camera also boasts a number of photography-based 4K features including Panasonic's 4K Photo mode which lets users select a single frame out of a 4K video to extract as a very usable 8-megapixel JPEG image. This is a function which was added via firmware to the GH4 and FZ1000, and has also featured on the LX100 and CM1 smartphone camera. In addition to extracting a still from a video, 4K photo bursts can also be recorded while the shutter button is pressed, using the shutter button to start and stop recording, or in a pre-burst mode which initiates a 4K video sequence one second before and after the shutter button is pressed, giving users 60 extra images to select from. This mode can be great for capturing very quick moments and impressed us when we tried it out on the CM1 smartphone camera, even though it only offered an additional 30 shots because of the slower frame-rate. Autofocus uses a contrast-based AF system which features 49 areas along with Panasonic's Depth From Defocus technology to ensure speedy and accurate subject acquisition with speeds of up to 0.07 seconds. A new algorithm is also said to vastly improve AF tracking by recognizing not only color, but also the size and motion vector of a target. Other autofocus modes include Eye Detection and Touch AF, while features like Focus Peaking are there for those who like to take a more manual approach. The Panasonic G7 is styled similarly to the GH4 and G6, and as such looks like a small modern DSLR. There's a chunky grip along with plenty of control dials for changing settings. It measures 124.9 x 86.2 x 77.4 mm (4.92 x 3.39 x 3.05 in) and weighs in at 410g (0.90 lb) with a battery and SD card. On the rear there's an OLED electronic viewfinder with 2,360k dots, and a three-inch free-angle LCD touchscreen with 1,040k dots. Other features of note include the ability to shoot and export time lapse videos, Low Light AF for focussing in -4EV low light conditions, and a Starlight AF mode which lets you shoot better images of the night sky. There's also the inclusion of built-in Wi-Fi which means the camera can be controlled remotely via a smart device, giving users the ability to remotely focus and shoot with a live preview, and then share the results. The Panasonic Lumix G7 is available for preorder now, and is expected to ship in June. It will set you back US$800 with a 14-42-mm kit lens, or $1,100 with a 14-140-mm lens.   Product page: Panasonic Lumix G7

World's longest glass bridge set to open in China next year

 

An artist's concept of people walking across the glass bridge high above the Zhangjiajie canyon in China (Credit: Haim Dotan Ltd) Image Gallery (5 images) In a bid to attract more tourists to the region, Hunan Province in China has commissioned the architectural firm of Haim Dotan to produce a completely transparent glass bridge spanning 370 m (1,214 ft) across the Zhangjiajie Grand Canyon. Dizzyingly high at about 400 m (1,312 ft) above the canyon floor, the span is claimed to be capable of holding up to 800 people at a time. China seems to be enamored with terrifyingly high, world-beating glass structures. Gizmag recently detailed the world's longest glass-bottomed cantilever skywalk in Longgang National Geological Park, Chongqing, for example, which extends 26.64 m (87.4 ft) over a straight drop of 718 m (2,356 ft), making it some 5 m (16 ft) longer than the Grand Canyon Skywalk in Arizona. The Zhangjiajie Grand Canyon glass bridge continues this trend of oneupmanship. Funded as part the Tourism investment cooperation meeting at the Central China Expo in 2012, and slated for opening some time next year, the glass bridge is touted as a "Wonder of the World" by Hunan Province. Set to be constructed between the summits either side of the canyon, the deceptively fragile-looking structure will also have an added thrill for those that find the idea of walking across a sheer drop on a see-through bridge too tame: A bungee jump. To be located in the middle of the structure, the bungee jump is also said to be another world-first for Hunan province as the highest bungee on the planet, at around 60 m (197 ft) or so higher than the current highest commercial bungee of 233 m (764 ft) on the Macau Tower. Sources: Haim Dotan, China Glass Network