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Google supercomputers rank billions of drug interactions and predict mechanisms of action solely through computation

Google supercomputers rank billions of drug interactions and predict mechanisms of action solely through computation | Amazing Science | Scoop.it

For decades, drug development was mostly a game of trial and error, with brute-force candidate screens throwing up millions more duds than winners. Researchers are now using computers to get a head start. By analysing the chemical structure of a drug, they can see if it is likely to bind to, or ‘dock’ with, a biological target such as a protein. Such algorithms are particularly useful for finding potentially toxic side effects that may come from unintended dockings to structurally similar, but untargeted, proteins.

 

Last week, researchers presented a computational effort that assesses billions of potential dockings on the basis of drug and protein information held in public databases. “It’s the largest computational docking ever done by mankind,” says Timothy Cardozo, a pharmacologist at New York University’s Langone Medical Center, who presented the project on 19 November at the US National Institutes of Health’s High Risk–High Reward Symposium in Bethesda, Maryland. The result, a website called Drugable (drugable.com) that is backed by the US National Library of Medicine (NLM), is still in testing, but it will eventually be available for free, allowing researchers to predict how and where a compound might work in the body, purely on the basis of chemical structure.


Predicting how untested compounds will interact with proteins in the body, as Drugable attempts to do, is more challenging. In setting up the website, Cardozo’s group selected about 600,000 molecules from PubChem and the European Bioinformatics Institute’s ChEMBL, which together catalogue millions of publicly available compounds. The group evaluated how strongly these molecules would bind to 7,000 structural ‘pockets’ on human proteins also described in the databases. Computing giant Google awarded the researchers the equivalent of more than 100 million hours of processor time on its supercomputers for the mammoth effort.

 

Cardozo acknowledges that the computations are just an initial step in drug discovery. After predicting whether a protein can bind to a compound, drug developers must test the drug’s action on the same protein in a cell to see what actually happens to the protein’s function, as well as how much of the drug is needed and under what conditions. Then come animal trials and, if researchers are lucky, human trials. But these extra data are often proprietary and held by pharmaceutical companies, says Brian Shoichet, a computational biologist at the University of California, San Francisco. Some public databases such as PubChem, maintained by the NLM, hold the results of automated tests of drugs on proteins in yeast cells, but they contain inaccuracies and false positives, he says.

 

Pharmaceutical companies have been doing similar computational predictions for years, says Jeremy Jenkins, a researcher at the Novartis Institutes. But he says that Novartis, which has a library of 1.5 million public and proprietary compounds, has never attempted to analyse as many proteins and drugs at once as Drugable has done.

 

Cardozo hopes that Drugable will be particularly helpful in evaluating psychiatric drugs, which often act in ways that are difficult to measure. As a demonstration, Cardozo’s group applied Drugable’s algorithm to clozapine and chlorpromazine, two drugs often prescribed to treat schizophrenia.

 

As expected, Drugable showed that the two drugs bind most strongly to receptors for the neurotransmitters serotonin and dopamine, which are expressed in the parts of the brain involved in higher information processing. But it found that clozapine, which also stabilizes mood disorders such as depression, binds strongly to a particular dopamine receptor called DRD4, which is expressed in the brain’s pineal gland — a known mood regulator.

 

The group also found that clozapine binds to a receptor in the part of the brain that regulates saliva production; excessive salivation is a known side effect of clozapine. Although the biochemical explanations for mood regulation and salivation have been proposed before, Cardozo says that Drugable can be used to reveal the most plausible mechanisms.

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Panel says, global warming carries risk of deep dramatic changes

Panel says, global warming carries risk of deep dramatic changes | Amazing Science | Scoop.it
Articles in the Temperature Rising series from The New York Times.

 

Continued global warming poses a risk of rapid, drastic changes in some human and natural systems, a scientific panel warned Tuesday, citing the possible collapse of polar sea ice, the potential for a mass extinction of plant and animal life and the threat of immense dead zones in the ocean. Articles in this series focus on the central arguments in the climate debate and examine the evidence for global warming and its consequences.

 

At the same time, some worst-case fears about climate change that have entered the popular imagination can be ruled out as unlikely, at least over the next century, the panel found. These include a sudden belch of methane from the ocean or the Arctic that would fry the planet, as well as a shutdown of the heat circulation in the Atlantic Ocean that would chill nearby land areas — the fear on which the 2004 movie “The Day After Tomorrow” was loosely based.

 

In a recent report, the panel appointed by the National Research Council called for the creation of an early warning system to alert society well in advance to changes capable of producing chaos. Nasty climate surprises have occurred already, and more seem inevitable, perhaps within decades, panel members warned. But, they said, little has been done to prepare.

 

“The reality is that the climate is changing,” said James W. C. White, a paleoclimatologist at the University of Colorado Boulder who headed the committee on abrupt impacts of climate change. “It’s going to continue to happen, and it’s going to be part of everyday life for centuries to come — perhaps longer than that.”

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New sperm 'blocking' method found: Male contraceptive could be on the horizon

New sperm 'blocking' method found: Male contraceptive could be on the horizon | Amazing Science | Scoop.it
Scientists have identified a way to block sperm transport during ejaculation, which could lead to a male contraceptive pill.

 

Published in the journal, Proceedings of the National Academy of Science, USA, scientists have found that complete male infertility could be achieved by blocking two proteins found on the smooth muscle cells that trigger the transport of sperm.

 

The researchers demonstrated that the absence of two proteins in mouse models, α1A-adrenoceptor and P2X1-purinoceptor, which mediate sperm transport, caused infertility, without effects on long-term sexual behavior or function.

 

Lead researchers, Dr. Sab Ventura and Dr. Carl White of the Monash Institute of Pharmaceutical Sciences, believe the knowledge could be applied to the potential development of a contraceptive pill for men.

 

“Previous strategies have focused on hormonal targets or mechanisms thatproduce dysfunctional sperm incapable of fertilization, but they often interfere with male sexual activity and cause long term irreversible effects on fertility,” Dr. Ventura said.

 

“We’ve shown that simultaneously disrupting the two proteins that control the transport of sperm during ejaculation causes complete male infertility, but without affecting the long-term viability of sperm or the sexual or general health of males. The sperm is effectively there but the muscle is just not receiving the chemical message to move it.

 

Dr. Ventura said there was already a drug that targets one of the two proteins, but they would have to find a chemical and develop a drug to block the second one.

 

“This suggests a therapeutic target for male contraception. The next step is to look at developing an oral male contraceptive drug, which is effective, safe, and readily reversible.” If successful, it is hoped a male contraceptive pill could be available within ten years.

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Benjamin Ebzery's curator insight, June 22, 2015 8:14 PM

This article is about a male version of a female contraceptive pill that stops the male sperm from leaving during male ejaculation. 

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The Bio-intelligence Explosion

The Bio-intelligence Explosion | Amazing Science | Scoop.it
How recursively self-improving organic robots will modify their own source code and bootstrap our way to full-spectrum superintelligence.
Via Szabolcs Kósa
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Super-thin membranes clear the way for chip-sized pumps

Super-thin membranes clear the way for chip-sized pumps | Amazing Science | Scoop.it

The ability to shrink laboratory-scale processes to automated chip-sized systems would revolutionize biotechnology and medicine. For example, inexpensive and highly portable devices that process blood samples to detect biological agents such as anthrax are needed by the U.S. military and for homeland security efforts. One of the challenges of "lab-on-a-chip" technology is the need for miniaturized pumps to move solutions through micro-channels. Electroosmotic pumps (EOPs), devices in which fluids appear to magically move through porous media in the presence of an electric field, are ideal because they can be readily miniaturized. EOPs however, require bulky, external power sources, which defeats the concept of portability. But a super-thin silicon membrane developed at the University of Rochester could now make it possible to drastically shrink the power source, paving the way for diagnostic devices the size of a credit card.

 

"Up until now, electroosmotic pumps have had to operate at a very high voltage—about 10 kilovolts," said James McGrath, associate professor of biomedical engineering. "Our device works in the range of one-quarter of a volt, which means it can be integrated into devices and powered with small batteries."

 

McGrath and his team use porous nanocrystalline silicon (pnc-Si) membranes that are microscopically thin—it takes more than one thousand stacked on top of each other to equal the width of a human hair. And that's what allows for a low-voltage system.

 

A porous membrane needs to be placed between two electrodes in order to create what's known as electroosmotic flow, which occurs when an electric field interacts with ions on a charged surface, causing fluids to move through channels. The membranes previously used in EOPs have resulted in a significant voltage drop between the electrodes, forcing engineers to begin with bulky, high-voltage power sources. The thin pnc Si membranes allow the electrodes to be placed much closer to each other, creating a much stronger electric field with a much smaller drop in voltage. As a result, a smaller power source is needed.

 

A microfluidic bioreactors consists of two chambers separated by a nanoporous silicon membrane. It allows for flow-based assays using minimal amounts of reagent. The ultra-thin silicon membrane provides an excellent mimic of biological barrier properties. The shown image combines two exposures in order to capture the brighter and darker parts of the scene, which exceed the dynamic range of the camera sensor. The resulting composite is truer to what the eye actually sees.

 

Along with medical applications, it's been suggested that EOPs could be used to cool electronic devices. As electronic devices get smaller, components are packed more tightly, making it easier for the devices to overheat. With miniature power supplies, it may be possible to use EOPs to help cool laptops and other portable electronic devices.

 

McGrath said there's one other benefit to the silicon membranes. "Due to scalable fabrication methods, the nanocrystalline silicon membranes are inexpensive to make and can be easily integrated on silicon or silica-based microfluid chips."

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Memories may be passed down through generations in DNA, a process underlying cause of phobias

Memories may be passed down through generations in DNA, a process underlying cause of phobias | Amazing Science | Scoop.it

In a recent study, published in the journal of Nature Neuroscience, the researchers trained mice to fear the smell of cherry blossom using electric shocks before allowing them to breed. The offspring produced showed fearful responses to the odor of cherry blossom compared to a neutral odor, despite never having encountered them before. The following generation also showed the same behavior. This effect continued even if the mice had been fathered through artificial insemination.

 

The researchers found the brains of the trained mice and their offspring showed structural changes in areas used to detect the odor. The DNA of the animals also carried chemical changes, known as epigenetic methylation, on the gene responsible for detecting the odor. This suggests that experiences are somehow transferred from the brain into the genome, allowing them to be passed on to later generations.

 

The researchers now hope to carry out further work to understand how the information comes to be stored on the DNA in the first place.

They also want to explore whether similar effects can be seen in the genes of humans.

 

Prof. Marcus Pembrey, a paediatric geneticist at University College London, said the work provided "compelling evidence" for the biological transmission of memory. He added: "It addresses constitutional fearfulness that is highly relevant to phobias, anxiety and post-traumatic stress disorders, plus the controversial subject of transmission of the ‘memory’ of ancestral experience down the generations.

 

"It is high time public health researchers took human transgenerational responses seriously. "I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”

 

Prof. Wolf Reik, head of epigenetics at the Babraham Institute in Cambridge, said, however, further work was needed before such results could be applied to humans. He said: "These types of results are encouraging as they suggest that transgenerational inheritance exists and is mediated by epigenetics, but more careful mechanistic study of animal models is needed before extrapolating such findings to humans.”

 

Another study in mice has shown that their ability to remember can be effected by the presence of immune system factors in their mother's milk. Dr Miklos Toth, from Cornell University in New York, found that chemokines carried in a mother's milk caused changes in the brains of their offspring, affecting their memory in later life.

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How close are we to finding dark matter?

How close are we to finding dark matter? | Amazing Science | Scoop.it

Dark matter makes up about a quarter of the cosmos, but we still don't know what it is. As part of a two-part series called Light & Dark on BBC Four, physicist Jim Al-Khalili pondered how close we are to understanding the mysterious "dark stuff".

 

Given all the progress we've made in modern physics over the past century, you may be forgiven for thinking that physicists are approaching a complete understanding of what makes up everything in our Universe.

 

For example, all the publicity surrounding the discovery of the Higgs boson last year seemed to be suggesting that this was one of the final pieces of the jigsaw - that all the fundamental building blocks of reality were now known.

 

So it might come as something of a shock to many people to hear that we still don't know what 95% of the Universe is made of. The stars in galaxies revolve around like undissolved coffee granules on the surface of you mug of coffee just after you've stopped stirring it.


It's all rather embarrassing. Everything we see: our planet and everything on it, the moon, the other planets and their moons, the Sun, all the stars in the sky that make up our Milky Way galaxy, all the other billions of galaxies beyond with their stars and clouds of interstellar gas, as well as all the dead stars and black holes that we can no longer see; it all amounts to less than 5% of the Universe.

 

And we don't even know if space goes on for ever, what shape the Universe is, what caused the Big Bang that created it, even whether it is just one of many embedded multiverses.

 
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malik matwi's comment, December 13, 2015 3:17 PM
neither dark matter nor energy http://iiste.org/Journals/index.php/APTA/article/view/26837
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Smartphone Physicals Are Taking Off With Explosion of Apps, Attachments

Smartphone Physicals Are Taking Off With Explosion of Apps, Attachments | Amazing Science | Scoop.it

There’s no shortage of smartphone appsto help people track their health. And in recent months, medical apps have started growing up, leaving behind the novelty of attaching probes to a smartphone to offer, they hope, serious clinical tools.

 

Last month in a Ted Talk, Shiv Gaglani showed that a standard physical exam can now be done using only smartphone apps and attachments. From blood pressure cuff to stethoscope and otoscope — the thing the doctor uses to look in your ears — all of the doctor’s basic instruments are now available in “smart” format.

 

 


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odysseas spyroglou's curator insight, November 30, 2013 1:10 PM

Smartphones in the service of health industry.

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Signs of Aging, Even in the Embryo

Signs of Aging, Even in the Embryo | Amazing Science | Scoop.it
New research indicates that senescent cells, those that stop dividing, play an important role at both the dawn and dusk of life.

 

In 1961, two biologists named Leonard Hayflick and Paul Moorehead discovered that old age is built into our cells. At the time, many scientists believed that if healthy human cells were put in a flask with a steady supply of nutrients, they would multiply forever. But when Dr. Hayflick and Dr. Moorehead reared fetal human cells, that’s not what they found. Time and again, their cells would divide about 50 times and then simply stop.


In fact, it turned out, senescent cells are involved in many of the ravages of old age. Wrinkled skin, cataracts and arthritic joints are rife with senescent cells. When researchers rid mice of senescent cells, the animals become rejuvenated.

 

Given all this research, the last place you would expect to find senescent cells would be at the very start of life. But now three teams of scientists are reporting doing just that. For the first time, they have found senescent cells in embryos, and they have offered evidence that senescence is crucial to proper development.

 

The discoveries raise the prospect that the dawn and dusk of life are intimately connected. For life to get off to the right start, in other words, youth needs a splash of old age.

 

Scott Lowe, an expert on senescence at Memorial Sloan-Kettering Cancer Center who was not involved in the research, praised the studies for pointing to an unexpected role for senescence. He predicted they would provoke a spirited debate among developmental biologists who study how embryos form. “They’re going to really love it or really hate it,” Dr. Lowe said.

 

While senescence may be a powerful defense against cancer, however, it comes at a steep cost. Even as we escape cancer, we accumulate a growing supply of senescent cells. The chronic inflammation they trigger can damage surrounding tissue and harm our health.

 

In the mid-2000s, William Keyes, a biologist then at Cold Spring Harbor Laboratory on Long Island, was studying how senescence leads to aging with experiments on mice. By shutting down a gene called P63, he could accelerate the rate at which the mice accumulated senescent cells — and accelerate their aging.

 

To observe the senescent cells, Dr. Keyes added a special stain to the bodies of these mice. To see the difference between these mice and normal ones, Dr. Keyes added the same stain to normal mouse embryos.

Naturally, he expected that none of the cells in the normal mouse embryos would turn dark. After all, senescent cells had been found only in old or damaged tissues. Much to his surprise, however, Dr. Keyes found patches of senescent cells in the normal mouse embryos. Dr. Keyes decided to look again at those peculiar senescent cells in normal embryos. He and his colleaguesconfirmed that cells became senescent in many parts of an embryo, such as along the developing tips of the legs.

 

The researchers, however, found no evidence that the senescent cells in embryos have damaged DNA. That discovery raises the question of how the cells were triggered to become senescent. Dr. Keyes hypothesizes they did so in response to a signal from neighboring cells.

 

Once an embryonic cell becomes senescent, it does the two things that all senescent cells do: it stops dividing and it releases a special cocktail. 

The new experiments suggest that this cocktail plays a different role in the embryo than in the adult body. It may act as a signal to other cells to become different tissues. It may also tell those tissues to grow at different rates into different shapes.

 

Dr. Keyes suspects that the sculpting that senescent cells carry out may be crucial to the proper development of an embryo. Consequently, any disruption to senescent cells may have dire consequences. “Where we see senescence in the embryo is where we see a lot of different birth defects,” he said.


For an embryo to develop properly, signals have to be sent to the right places at the right times. The peculiar behavior of senescent cells may help in both regards. If a cell stops growing, it won’t spread too far from a particular spot in an embryo. And by summoning immune cells to kill it, a senescent cell may ensure that its signals don’t last too long.

 

It’s possible, Dr. Keyes speculates, that senescence actually evolved first as a way to shape embryos; only later in evolution did it take on a new role, as a weapon against cancer. “I like the idea that it was a simple process that was then modified,” Dr. Keyes said.

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Madison Punch's comment, March 24, 2014 7:14 PM
I found this article to be among the coolest I've read from scoop.it. I figured that aging came with the weakening, or rather aging, of the body. Who knew it was basically "installed" into our cells? The end of cell division basically stops the flourishing of the peak of life and begins to fall into aging. Very cool.
Madison Carson's comment, September 1, 2015 8:44 PM
I found this article to be rather cool. I've never heard of some of the cells that they were talking about. I thought that the older you got, the effects of old age would just come with it. But, seeing that old age is in you from the time you were born is very interesting.
andrea luan villa's comment, February 2, 6:58 PM
I didn't know that old age is built into our cells; that very cool. I also didn't know that embryos had senses. this interesting I learned a lot from it.
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Developing a Fax Machine to Copy Life on Mars

Developing a Fax Machine to Copy Life on Mars | Amazing Science | Scoop.it
DNA sequencing and DNA synthesis are becoming faster and cheaper, and J. Craig Venter wants to use the technology to bring Martian life to Earth.

 

 J. Craig Venter is looking for a new world to conquer — Mars. He wants to detect life on Mars and bring it to Earth using a device called a digital biological converter, or biological teleporter. Although the idea conjures up “Star Trek,” the analogy is not exact. The transporter on that program actually moves Captain Kirk from one location to another. Dr. Venter’s machine would merely create a copy of an organism from a distant location — more like a biological fax machine.


Still, Dr. Venter, known for his early sequencing of the human genome and for his bold proclamations, predicts the biological converter will be his next innovation and will be useful on Earth well before it could ever be deployed on the red planet.

 

The idea behind it, not original to him, is that the genetic code that governs life can be stored in a computer and transmitted just like any other information.

 

Dr. Venter’s system would determine the sequence of the DNA units in an organism’s genome and transmit that information electronically. At the distant location, the genome would be synthesized — or chemically recreated — inserted into what amounts to a blank cell, and “booted up,” as Mr. Venter puts it. In other words, the inserted DNA would take command of the cell and recreate a copy of the original organism.

 

To test some ideas, he and a small team of scientists from his company and from NASA spent the weekend here in the Mojave Desert, the closest stand-in they could find for the dry surface of Mars.

 

The biological fax is not as far-fetched as it seems. DNA sequencing and DNA synthesis are rapidly becoming faster and cheaper. For now, however, synthesizing an organism’s entire genome is still generally too difficult. So the system will first be used to remotely clone individual genes, or perhaps viruses. Single-celled organisms like bacteria might come later. More complex creatures, earthly or Martian, will probably never be possible.

 

Dr. Venter’s company, Synthetic Genomics, and his namesake nonprofit research institute have already used the technology to help develop an experimental vaccine for the H7N9 bird flu with the drug maker Novartis.

 

Typically, when a new strain of flu virus appears, scientists must transport it to labs, which can spend weeks perfecting a strain that can be grown in eggs or animal cells to make vaccine.

 

But when H7N9 appeared in China in February, its genome was sequenced by scientists there and made publicly available. Within days, Dr. Venter’s team had synthesized the two main genes and used them to make a vaccine strain, without having to wait for the virus to arrive from China.

 

Dr. Venter said Synthetic Genomics would start selling a machine next year that would automate the synthesis of genes by stringing small pieces of DNA together to make larger ones.

 

Eventually, he said, “we’ll have a small box like a printer attached to your computer.” A person with a bacterial infection might be sent the code to recreate a virus intended to kill that specific bacterium.

 

“We can send an antibiotic as an email,” said Dr. Venter, who has outlined his ideas in a new book, “Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life.” Proteins might also be made, so that diabetics, for instance, could “download insulin from the Internet.”

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A Thin Sheet of Reality: Discussion about the Universe as a Hologram (Full VIDEO)

From the World Science Festival 2011:

 

What we touch. What we smell. What we feel. They're all part of our reality. But what if life as we know it reflects only one side of the full story? Some of the world's leading physicists think that this may be the case. They believe that our reality is a projection—sort of like a hologram—of laws and processes that exist on a thin surface surrounding us at the edge of the universe. Although the notion seems outlandish, it's a long-standing theory that initially emerged years ago from scientists studying black holes; recently, a breakthrough in string theory propelled the idea into the mainstream of physics. What took place was an intriguing discussion on the cutting-edge results that may just change the way we view reality.

Panel includes John Hockenberry, an award-winning journalist with twenty-five years experience in radio, broadcast television and print. He is the host of WNYC and PRI's The Takeaway, a correspondent for PBS Frontline, and a noted presenter and moderator at conferences such at TED, Aspen Ideas, and the World Science Festival. 

Gerardus 't Hooft, born on July 5, 1946, in Den Helder, Netherlands. He received his doctorate in theoretical physics in 1972 at Utrecht University on "The Renormalization Procedure for Yang-Mills Fields", this work would later earn him, together with his advisor Martinus Veltman, the 1999 Nobel Prize in Physics. Dr. 't Hooft has been Professor in Theoretical Physics at Utrecht for most of his professional life, doing research and education on the topics of the electro-weak interaction, the strong interaction and later also the gravitational forces in the world of the sub-atomic particles. Member of the Dutch Academy of Sciences (KNAW) as well as other institutions and academies, his work led to a number of honorary doctorates and international prizes such as the Wolf Prize of Israel, the Pius XI Medal, and the Franklin Medal.

Leonard Susskind, the Felix Bloch Professor of Theoretical Physics at Stanford University, and one of the discoverers of string theory, a candidate for a theory that unifies all laws of physics. An award-winning author, he is a proponent of the idea that our universe is one of an infinite number. 

Herman Verlinde, a renowned physicist and influential contributor to string theory and its application in mathematics, particle physics, cosmology, and black hole physics. Herman Verlinde's research has been recognized through several awards and fellowships from the Packard Foundation, the Sloan Foundation, and the Royal Dutch Academy of Science. In 1988, Verlinde received his Ph.D. at Utrecht University under the supervision of Gerard't Hooft. From 1994 to 1998, he was professor of physics at the University of Amsterdam, where he founded its Center for Mathematical Physics. In 2008 and 2009, he was a visiting member at the Institute of Advanced Study in Princeton. Herman Verlinde is the twin brother of Erik Verlinde, who is also a prominent string theorist and professor of physics at the University of Amsterdam.

Raphael Bousso is recognized for discovering the general relation between the curved geometry of space-time and its information content, known as the "covariant entropy bound." This allowed for a precise and general formulation of the holographic principle, which is believed to underlie the unification of quantum theory and Einstein's theory of gravity. Bousso is also one of the discoverers of the landscape of string theory, which explains the small but non-vanishing value of the cosmological constant or "dark energy". His work has led to a novel view of cosmology, the multiverse of string theory. Bousso is currently professor of physics at the University of California, Berkeley.

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Big Weather Pattern on Hot Jupiter Exoplanets

Among the hundreds of new planets discovered by NASA's Kepler spacecraft are a class of exotic worlds known as "hot Jupiters."  Unlike the giant planets of our own solar system, which remain at a safe distance from the sun, these worlds are reckless visitors to their parent stars. They speed around in orbits a fraction the size of Mercury’s, blasted on just one-side by starlight hundreds of times more intense than the gentle heating experienced by Jupiter here at home. Meteorologists watching this video are probably wondering what kind of weather a world like that might have. The short answer is "big."

 

Heather Knutson of Caltech made the first weather map of a hot Jupiter in 2007. "It's not as simple as taking a picture and--voila!—we see the weather," says Knutson. These planets are hundreds of light years from Earth and they are nearly overwhelmed by the glare of their parent stars. "Even to see the planet as a single pixel next to the star would be a huge accomplishment."

 

Instead, Knutson and colleagues use a trick dreamed up by Nick Cowan of Northwestern University. The key, she explains, is that "most hot Jupiters are tidally locked to their stars. This means they have a permanent dayside and a permanent night side.  As we watch them orbit from our vantage point on Earth, the planets exhibit phases--e.g., crescent, gibbous and full.  By measuring the infrared brightness of the planet as a function of its phase, we can make a rudimentary map of temperature vs. longitude."

 

 This exoplanet weather map shows temperatures on a hot Jupiter known as "HAT-P-2b". NASA’s Spitzer Space Telescope is the only infrared observatory with the sensitivity to do this work.  Since Knutson kick-started the research in 2007, nearly a dozen hot Jupiters have been mapped by astronomers using Spitzer.

 

The most recent study, led by Nikole Lewis, a NASA Sagan Exoplanet Fellow working at MIT, shows a gas giant named HAT-P-2b. "We can see daytime temperatures as high as 2400 K," says Lewis, "while the nightside drops below 1200K.  Even at night," she marvels, "this planet is ten times hotter than Jupiter."

 

These exoplanet maps may seem crude compared to what we’re accustomed to on Earth, but they are a fantastic accomplishment considering that the planets are trillions of miles away.

 

The maps show huge day-night temperature differences typically exceeding 1000 degrees.  Researchers believe these thermal gradients drive ferocious winds blowing thousands of miles per hour.

 

Without regular pictures, researchers can’t say what this kind of windy weather looks like. Nevertheless, Knutson is willing to speculate using climate models of Jupiter as a guide. "Weather on hot Jupiters," she predicts, "is really big." 

 

Over the years, planetary scientists have developed computer models to reproduce the storms and cloud belts in Jupiter’s atmosphere.  If you take those models and turn up the heat, and slow down the rotation to match the tidally-locked spin of a hot Jupiter, weather patterns become super-sized. For instance, on a hot Jupiter the Great Red Spot might grow as large as a quarter the size of the planet and manifest itself in both the northern and southern hemispheres.


"Just imagine what that would look like--a pair of giant eyes staring out into space!" says Lewis. Meanwhile, Jupiter’s famous belts would widen so much that only two or three would fit across the planet’s girth. Ordinary clouds of water and methane couldn’t form in such a hot environment. Instead, Knutson speculates that hot Jupiters might have clouds made of silicate—that is, "rock clouds."

 

"Silicates are predicted to condense in such an environment," she says. "We're already getting some hints that clouds might be common on these planets, but we don’t yet know if they’re made of rock." For now just one thing is certain: The meteorology of hot Jupiters is out of this world.

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No more injections? Nanoparticles as pills of the future

No more injections? Nanoparticles as pills of the future | Amazing Science | Scoop.it
Researchers design drug-carrying nanoparticles that can be taken orally

 

Several types of nanoparticles carrying chemotherapy drugs or short interfering RNA, which can turn off selected genes, are now in clinical trials to treat cancer and other diseases. These particles exploit the fact that tumors and other diseased tissues are surrounded by leaky blood vessels. After the particles are intravenously injected into patients, they seep through those leaky vessels and release their payload at the tumor site. 

For nanoparticles to be taken orally, they need to be able to get through the intestinal lining, which is made of a layer of epithelial cells that join together to form impenetrable barriers called tight junctions.

“The key challenge is how to make a nanoparticle get through this barrier of cells. Whenever cells want to form a barrier, they make these attachments from cell to cell, analogous to a brick wall where the bricks are the cells and the mortar is the attachments, and nothing can penetrate that wall,” Farokhzad says.

Researchers have previously tried to break through this wall by temporarily disrupting the tight junctions, allowing drugs through. However, this approach can have unwanted side effects because when the barriers are broken, harmful bacteria can also get through. 

To build nanoparticles that can selectively break through the barrier, the researchers took advantage of previous work that revealed how babies absorb antibodies from their mothers’ milk, boosting their own immune defenses. Those antibodies grab onto a cell surface receptor called the FcRN, granting them access through the cells of the intestinal lining into adjacent blood vessels. 

The researchers coated their nanoparticles with Fc proteins — the part of the antibody that binds to the FcRN receptor, which is also found in adult intestinal cells. The nanoparticles, made of a biocompatible polymer called PLA-PEG, can carry a large drug payload, such as insulin, in their core. 

After the particles are ingested, the Fc proteins grab on to the FcRN in the intestinal lining and gain entry, bringing the entire nanoparticle along with them. 

“It illustrates a very general concept where we can use these receptors to traffic nanoparticles that could contain pretty much anything. Any molecule that has difficulty crossing the barrier could be loaded in the nanoparticle and trafficked across,” Karnik says. 

The researchers’ discovery of how this type of particle can penetrate cells is a key step to achieving oral nanoparticle delivery, says Edith Mathiowitz, a professor of molecular pharmacology, physiology, and biotechnology at Brown University.

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Half of all US clinical trials go unpublished

Half of all US clinical trials go unpublished | Amazing Science | Scoop.it

Clinical trials — which usually compare the effectiveness of medical treatments to placebos — often get published in peer-reviewed journals only if they gave favourable results. The results of clinical trials are going unpublished as much as half the time, and those that are published omit some key details, a study has found.


US law requires the results of medical research for drugs approved by the US Food and Drug Administration to be submitted to a database called ClinicalTrials.gov. Results, including adverse effects, have been made public there since 2008. Researchers who do not post results within a year of trial completion risk losing grants and can be fined as much as US$10,000 per day. But the database was never meant to replace journal publications, which often contain longer descriptions of methods and results and are the basis for big reviews of research on a given drug.

 

In an analysis of 600 trials picked at random from the database, Agnes Dechartres, an epidemiologist at Paris Descartes University, and her colleagues have now found that only 50% had made their way into print. “Non-publication is a crucial problem for all stakeholders, from patients to health policy-makers,” says Dechartres. For one thing, she says, failure to publish results in journals breeches the implied contract with patients who participated in the trials. “If results are not [fully] available, we can consider that research wasted,” she says.

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Signature of Water Found on 5 Exoplanets by Hubble Telescope

Signature of Water Found on 5 Exoplanets by Hubble Telescope | Amazing Science | Scoop.it
NASA's Hubble Space Telescope has detected water in the atmospheres of five planets beyond our solar system, two recent studies reveal.

 

The five exoplanets with hints of water are all scorching-hot, Jupiter-size worlds that are unlikely to host life as we know it. But finding water in their atmospheres still marks a step forward in the search for distant planets that may be capable of supporting alien life, researchers said.

 

"We're very confident that we see a water signature for multiple planets," Avi Mandell, of NASA's Goddard Space Flight Center in Greenbelt, Md., lead author of one of the studies, said in a statement. "This work really opens the door for comparing how much water is present in atmospheres on different kinds of exoplanets — for example, hotter versus cooler ones."

 

The two research teams used Hubble's Wide Field Camera 3 to analyze starlight passing through the atmospheres of the five "hot Jupiter" planets, which are known as WASP-17b, HD209458b, WASP-12b, WASP-19b and XO-1b.

 

The atmospheres of all five planets showed signs of water, with the strongest signatures found in the air of WASP-17b and HD209458b. "To actually detect the atmosphere of an exoplanet is extraordinarily difficult. But we were able to pull out a very clear signal, and it is water," Drake Deming of the University of Maryland, lead author of the other recent study, said in a statement.

 

Water is thought to be a common constituent of exoplanet atmospheres and has been found in the air of several other distant worlds to date. But the new work marks the first time scientists have measured and compared profiles of the substance in detail across multiple alien worlds, researchers said.

 

"These studies, combined with other Hubble observations, are showing us that there are a surprisingly large number of systems for which the signal of water is either attenuated or completely absent," Heather Knutson of the California Institute of Technology in Pasadena, a co-author on Deming's paper, said in a statement. "This suggests that cloudy or hazy atmospheres may in fact be rather common for hot Jupiters."

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Neuroengineering - Engineering Memories - The Future is Now

Dr. Theodore Berger's research is currently focused primarily on the hippocampus, a neural system essential for learning and memory functions.


Theodore Berger leads a multi-disciplinary collaboration with Drs. Marmarelis, Song, Granacki, Heck, and Liu at the University of Southern California, Dr. Cheung at City University of Hong Kong, Drs. Hampson and Deadwyler at Wake Forest University, and Dr. Gerhardt at the University of Kentucky, that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for long-term memory. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease), and is considered to underlie the memory deficits characteristic of these neurological conditions.


The essential goals of Dr. Berger's multi-laboratory effort include: (1) experimental study of neuron and neural network function during memory formation -- how does the hippocampus encode information?, (2) formulation of biologically realistic models of neural system dynamics -- can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event?, (3) microchip implementation of neural system models -- can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization?, and (4) creation of conformal neuron-electrode interfaces -- can cytoarchitectonic-appropriate multi-electrode arrays be created to optimize bi-directional communication with the brain? By integrating solutions to these component problems, the team is realizing a biomimetic model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus.

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Neurobiologists investigate neuronal basis intelligence in birds

Neurobiologists investigate neuronal basis intelligence in birds | Amazing Science | Scoop.it
Scientists have long suspected that corvids – the family of birds including ravens, crows and magpies – are highly intelligent.

 

The Tübingen researchers are the first to investigate the brain physiology of crows' intelligent behavior. They trained crows to carry out memory tests on a computer. The crows were shown an image and had to remember it. Shortly afterwards, they had to select one of two test images on a touchscreen with their beaks based on a switching behavioral rules. One of the test images was identical to the first image, the other different. Sometimes the rule of the game was to select the same image, and sometimes it was to select the different one. The crows were able to carry out both tasks and to switch between them as appropriate. That demonstrates a high level of concentration and mental flexibility which few animal species can manage – and which is an effort even for humans.

 

The crows were quickly able to carry out these tasks even when given new sets of images. The researchers observed neuronal activity in the nidopallium caudolaterale, a brain region associated with the highest levels of cognition in birds. One group of nerve cells responded exclusively when the crows had to choose the same image – while another group of cells always responded when they were operating on the "different image" rule. By observing this cell activity, the researchers were often able to predict which rule the crow was following even before it made its choice.

 

The study published in Nature Communications provides valuable insights into the parallel evolution of intelligent behavior. "Many functions are realized differently in birds because a long evolutionary history separates us from these direct descendants of the dinosaurs," says Lena Veit. "This means that bird brains can show us an alternative solution out of how intelligent behavior is produced with a different anatomy." Crows and primates have different brains, but the cells regulating decision-making are very similar. They represent a general principle which has re-emerged throughout the history of evolution. "Just as we can draw valid conclusions on aerodynamics from a comparison of the very differently constructed wings of birds and bats, here we are able to draw conclusions about how the brain works by investigating the functional similarities and differences of the relevant brain areas in avian and mammalian brains," says Professor Andreas Nieder.

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Photon-plasmon nanowire laser offers new opportunities in light manipulation

Photon-plasmon nanowire laser offers new opportunities in light manipulation | Amazing Science | Scoop.it
Recently, researchers have been developing a new type of laser that combines photons and plasmons (electron density oscillations) into a single radiation-emitting device with unique properties.

 

The hybrid photon-plasmon nanowire laser is composed of a Ag nanowire and a CdSe nanowire coupled into an X-shape. This type of coupling enables the photonic and plasmonic modes to be separated, which gives the hybrid laser advantageous features.


"Compared to conventional photon lasers, the hybrid photon-plasmon nanowire laser offers two outstanding possibilities: the extremely thin laser beam (e.g., down to the size of a single molecule) and the ultrafast modulation (e.g., >THz repetition rate), both stemming from the longitudinally separable pure plasmon nanowire mode," Limin Tong, Professor at Zhejiang University in Hangzhou China, told Phys.org. "Owing to the above-mentioned merits, photon-plasmon lasers are potentially better for certain applications such as strong coupling of quantum nanoemitters, ultra-sensitivity optical sensing, and ultrafast-modulated coherent sources."


In a new study, the researchers have demonstrated that the photon and plasmon nanowire waveguides can be coupled in the longitudinal direction; that is, along the direction of the beams. This type of coupling makes it possible to spatially separate the plasmonic mode from the photonic mode, and to simultaneously use both modes. Under excitation, strong luminous spots are observed at both ends of the hybrid cavity, with interference rings indicating strong spatial coherence of the light emitted. The output spot of the Ag nanowire is much smaller than that of the CdSe nanowire, indicating much tighter confinement of the plasmon radiation.


The advantages of ultratight confinement and ultrafast modulation offered by side-coupling a plasmonic nanowire waveguide to a photonic one enable the hybrid laser to provide very precise lasing, which could be delivered to very small areas such as quantum dots. Photon-plasmon lasers can also have applications for nanophotonic circuits, biosensing, and quantum information processing. The researchers plan to make further improvements to the laser in the future.

 

"One of our future plans is to introduce the ultrafast nonlinear effects of the plasmonic nanowire into the hybrid laser, and explore the possibility of ultrafast-modulation of the nanolaser, while offering a far-field-accessible pure plasmon cavity mode with sub-diffration-limited beam size," Tong said.

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AIXI: To create a super-intelligent machine, start with an equation

AIXI: To create a super-intelligent machine, start with an equation | Amazing Science | Scoop.it
Intelligence is a very difficult concept and, until recently, no one has succeeded in giving it a satisfactory formal definition.

 

Most researchers have given up grappling with the notion of intelligence in full generality, and instead focus on related but more limited concepts – but Marcus Hutter argues that mathematically defining intelligence is not only possible, but crucial to understanding and developing super-intelligent machines. From this, his research group has even successfully developed software that can learn to play computer games from scratch.

 

But first, how do we define "intelligence"? Hutter's group has sifted through the psychology, philosophy and artificial intelligence literature and searched for definitions individual researchers and groups came up with. The characterizations are very diverse, but there seems to be a recurrent theme which we have aggregated and distilled into the following definition: Intelligence is an agent's ability to achieve goals or succeed in a wide range of environments.

 

The emerging scientific field is called universal artificial intelligence, with AIXI being the resulting super-intelligent agent. AIXI has a planning component and a learning component. The goal of AIXI is to maximise its reward over its lifetime – that's the planning part.

 

In summary, every interaction cycle consists of observation, learning, prediction, planning, decision, action and reward, followed by the next cycle. If you're interested in exploring further, AIXI integrates numerous philosophical, computational and statistical principles:

 

  • Ockham's razor (simplicity) principle for model selection
  • Epicurus principle of multiple explanations as a justification of model averaging
  • Bayes rule for updating beliefs
  • Turing machines as universal description language
  • Kolmogorov complexity to quantify simplicity
  • Solomonoff's universal prior, and
  • Bellman equations for sequential decision making.

 

AIXI's algorithm rigorously and uniquely defines a super-intelligent agent that learns to act optimally in arbitrary unknown environments. One can prove amazing properties of this agent – in fact, one can prove that in a certain sense AIXI is the most intelligent system possible. Note that this is a rather coarse translation and aggregation of the mathematical theorems into words, but that is the essence.

 

Since AIXI is incomputable, it has to be approximated in practice. In recent years, we have developed various approximations, ranging from provably optimal to practically feasible algorithms.

 

The point is not that AIXI is able to play these games (they are not hard) – the remarkable fact is that a single agent can learn autonomously this wide variety of environments. AIXI is given no prior knowledge about these games; it is not even told the rules of the games! It starts as a blank canvas, and just by interacting with these environments, it figures out what is going on and learns how to behave well. This is the really impressive feature of AIXI and its main difference to most other projects.

 

Even though IBM Deep Blue plays better chess than human Grand Masters, it was specifically designed to do so and cannot play Jeopardy. Conversely, IBM Watson beats humans in Jeopardy but cannot play chess – not even TicTacToe or Pac-Man. AIXI is not tailored to any particular application. If you interface it with any problem, it will learn to act well and indeed optimally.

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The world’s oldest astronomers: Scientists use ancient trees to look back on the history of our local cosmos

The world’s oldest astronomers: Scientists use ancient trees to look back on the history of our local cosmos | Amazing Science | Scoop.it
Scientists in Japan use ancient trees to look back on the history of our local cosmos, and discover a mystery.

 

Since the invention of the telescope in the year 1608, mankind has collected information about our local cosmos. As it turns out, we’re not the only ones. Trees have been doing the same for millennia.

 

A group of physicists led by Nagoya University graduate student Fusa Miyake has begun using information stored in ancient Japanese cedars to gain the oldest firsthand accounts of the local universe. They have discovered, hidden within tree rings, clear evidence of some surprisingly high-energy events—possibly supernovae or solar flares—that occurred more than 1200 years ago.

 

On Japan’s Yakushima island, trees regularly live at least a thousand years, thriving under the tree equivalent of a low-carb diet in the form of a low-nutrition granite bedrock that encourages a slower pace of growth. Miyake and her team examined core samples from two trees on this small island. Back at Nagoya University, they studied the number and thickness of the tree’s rings not just to determine the age of the trees but also to gather information about the atmosphere they breathed.


When high-energy radiation from space enters Earth’s upper atmosphere, it interacts with naturally occurring atmospheric molecules to produce the isotope carbon-14. As trees are firmly plugged into the earth’s carbon cycle by photosynthesis, the carbon-14 ends up in each tree ring, creating an annual record etched into the flesh of the tree of the average carbon-14 level in Earth’s atmosphere.

 

Miyake and her colleagues had good reason to focus on the rings corresponding to 775 AD. A previous project called IntCal, which uses tree records of carbon-14 levels to calibrate carbon-14 dating, had seen a noticeable rise in carbon-14 levels toward the end of the 8th century.

The signal Miyake’s team found was far above anything seen in recent times, indicating that Earth had been bombarded by an extremely intense burst of radiation. The rings revealed that, over the course of one year, the atmospheric level of carbon-14 rose 1.2 percent: nearly 20 times the normal variation.

 

This massive flash of radiation could have been caused by a supernova; a gamma ray burst from a supremely rare galactic event such as a collision of two neutron stars; or a super solar flare at least 10 times the size of the largest observed flare.

 

Using their knowledge of earth sciences, biology and astronomy, Miyake’s team uncovered a smoking gun in a cosmological whodunit. Now all that remains is to identify who fired that gun.

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Abel Farias's curator insight, December 2, 2013 5:38 PM

You can find history in any object. Whenever archeologists look for new fossils they are looking for a something that tells them a story. In this article they talk about how tree rings explain how the environment was during the life of the tree. I would use this article in Chemistry class during the Carbon Dating unit. It shows how recent day scientist used carbon dating to make a new discovery

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Ultrasound pulses could replace daily injections for diabetics

Ultrasound pulses could replace daily injections for diabetics | Amazing Science | Scoop.it

There could be hope for diabetics who are tired of giving themselves insulin injections on a daily basis. Researchers at North Carolina State University and the University of North Carolina at Chapel Hill are developing a system in which a single injection of nanoparticles could deliver insulin internally for days at a time – with a little help from pulses of ultrasound.

 

The biocompatible and biodegradable nanoparticles are made of poly(lactic-co-glycolic acid), and contain a payload of insulin. Each particle has either a positively-charged chitosan coating, or a negatively-charged alginate coating. When the two types of particles are mixed together, these oppositely-charged coatings cause them to be drawn to each other by electrostatic force.

 

 


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Joseph Perrone's comment, January 12, 2014 12:35 PM
Researchers in north Carolina are developing a way to help people with diabetes. so instead of giving insulin shots every day they are working on a way to use one shot and use that for days on end with the use of ultrasounds. This will make it much easier on the people who take the shots every single day. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I really think that this will be very useful to the diabetics! sounds much better that giving yourself a shot everyday! Must be painful to do that stuff. Good artical!
Taylor Marie Price's comment, February 5, 2014 5:18 PM
UNC and NC State students are trying to develop a way for diabetics to receive their insulin without daily injections. The plan is for nanoparticles to carry a payload of insulin to last a few days...................................As a diabetic I think it is a great idea and would be absolutely AMAZING!!! Even though I'm currently on a insulin pump which allows less shots it would even better if I had something that worked in the way the nanoparticles would work so it would allow me to not have to worry about forgetting as often or having to stress about giving my insulin to myself.
Madison Punch's comment, April 13, 2014 2:36 PM
It's so cool to know that in my home state, students are trying to improve treatment mediums for diabetics. It's a tough thing to deal with and to control and it's rad that more ways to accommodate the disease.
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Ash on the fire: Why do dying stars accumulate iron?

Ash on the fire: Why do dying stars accumulate iron? | Amazing Science | Scoop.it

Every now and again a physicist finds themselves in front of a camera and, either through over-enthusiasm or poor editing, is heard to say something that is “less nuanced” than they may have intended.  “Iron kills stars” is one of the classics.

 

Just to be clear, if you chuck a bunch of iron into a star, you’ll end up with a lot of vaporized iron that you’ll never get back.  The star itself will do just fine.  The Earth is about 1/3 iron (effectively all of that is in the core), but even if you tossed the entire Earth into the Sun, the most you’d do is upset Al Gore.

 

Stars are always in a balance between their own massive weight that tries to crush their cores, and the heat generated by fusion reactions in the core that pushes all that weight back out.  The more the core is crushed, the hotter and denser it gets, which increases the rate of fusion reactions (increases the cores rate of “explodingness”), which pushes the bulk of the Star away from the core again.  As long as there’s “fuel” in the core, and attempt to crush it will result in the core pushing back.

 

Young stars burn hydrogen, because hydrogen is the easiest element to fuse and also produces the biggest bang.  But hydrogen is the lightest element, which means that older stars end up with a bunch of heavier stuff, like carbon and oxygen and whatnot, cluttering up their cores.  But even that isn’t terribly bad news for the star.  Those new elements can also fuse and produce enough new energy to keep the core from being crushed.  The problem is, when heavier elements fuse they produce less energy than hydrogen did.  So more fuel is needed.  Generally speaking, the heavier the element, the less bang-for-the-buck.

 

Iron is where that slows to a stop.  Iron collecting in the core is like ash collecting in a fire.  It’s not that it somehow actively stops the process, but at the same time: it doesn’t help.  Throw wood on a fire, you get more fire.  Throw ash on a fire, you get hot ash.

 

So, iron doesn’t kill stars so much as it is a symptom of a star that’s about to be done.  Without fuel, the rest of the star is free to collapse the core without opposition, and generally it does.  When there’s a lot of iron being produced in the core, a star probably only has a few hours or seconds left to live.

 

Of course there are elements heavier than iron, and they can undergo fusion as well.  However, rather than producing energy, these elements require additional energy to be created (throwing liquid nitrogen on a fire, maybe?).  That extra energy (which is a lot) isn’t generally available until the outer layers of the star come crushing down on the core.  The energy of all that falling material drives the fusion rate of the remaining lighter elements way, way, way up (supernovas are super for a reason), and also helps power the creation of the elements that make our lives that much more interesting: gold, silver, uranium, lead, mercury, whatever.

 

There are more than a hundred known elements, and iron is only #26.  Basically, if it’s heavy, it’s from a supernova.  Long story short: iron doesn’t kill stars, but right before a (large) star dies, it is full of buckets of iron.

 
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Abel Farias's curator insight, December 2, 2013 5:11 PM

Think Astronomy class. Students are always wondering why stars shine or why they are in the sky. This article opens up another can of worms to intrigue students into further thinking. I would recommend this in a chemistry, physics or astronomy class. It provides information that you can piggy back off of what you would like to teach. For chemistry I would use it to explain properties of elements. 

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Novel gene therapy works to reverse heart failure

Novel gene therapy works to reverse heart failure | Amazing Science | Scoop.it
Researchers have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in large animal models.

 

Researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in large animal models.


The new research study findings, published in November 13 issue of Science Translational Medicine, is the final study phase before human clinical trials can begin testing SUMO-1 gene therapy. SUMO-1 is a gene that is "missing in action" in heart failure patients.


"SUMO-1 gene therapy may be one of the first treatments that can actually shrink enlarged hearts and significantly improve a damaged heart's life-sustaining function," says the study's senior investigator Roger J. Hajjar, MD, Director of the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai and the Arthur & Janet C. Ross Professor of Medicine at Mount Sinai. "We are very eager to test this gene therapy in our patients suffering from severe heart failure."

 

Heart failure remains a leading cause of hospitalization in the elderly. It accounts for about 300,000 deaths each year in the United States. Heart failure occurs when a person's heart is too weak to properly pump and circulate blood throughout their body.

 

Dr. Hajjar is already on a path toward approval from the Food and Drug Administration to test the novel SUMO-1 gene therapy in heart failure patients. When it begins, the clinical trial will be the second gene therapy treatment designed to reverse heart failure launched by Dr. Hajjar and his Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai.

 

The first trial, named CUPID, is in its final phases of testing SERCA2 gene therapy. Phase 1 and phase 2a trial results were positive, demonstrating substantial improvement in clinical events.

 

In that trial, a gene known as SERCA2 is delivered via an inert virus -- a modified virus without infectious particles. SERCA2 is a gene that produces an enzyme critical to the proper pumping of calcium out of cells. In heart failure, SERCA2 is dysfunctional, forcing the heart to work harder and in the process, to grow larger.

 

The virus carrying SERCA2 is delivered through the coronary arteries into the heart during a cardiac catheterization procedure. Studies show only a one-time gene therapy dose is needed to restore healthy SERCA2a gene production of its beneficial enzyme. But previous research by Mount Sinai discovered SERCA2 is not the only enzyme that is missing in action in heart failure.

 

A study published in Nature in 2011 by Dr. Hajjar and his research group showed that the SUMO-1 gene is also decreased in failing human hearts. But SUMO-1 regulates SERCA2a's activity, suggesting that it can enhance the function of SERCA2a without altering its levels. A follow-up study in a mouse model of heart failure demonstrated that SUMO-1 gene therapy substantially improved cardiac function.

 

This new study tested delivery of SUMO-1 gene therapy alone, SERCA2 gene therapy alone, and a combination of SUMO-1 and SERCA2.

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3D Cosmography of the Local Universe - a film by Hélène Courtois

The large scale structure of the universe is a complex web of clusters, filaments, and voids. Its properties are informed by galaxy redshift surveys and measurements of peculiar velocities. Wiener Filter reconstructions recover three-dimensional velocity and total density fields. The richness of the elements of our neighborhood are revealed with sophisticated visualization tools.


The ability to translate and zoom helps the viewer follow structures in three dimensions and grasp the relationships between features on different scales while retaining a sense of orientation. The ability to dissolve between scenes provides a technique for comparing different information, for example, the observed distribution of galaxies, smoothed representations of the distribution accounting for selection effects, observed peculiar velocities, smoothed and modeled representations of those velocities, and inferred underlying density fields.


The agreement between the large scale structure seen in redshift surveys and that inferred from reconstructions based on the radial peculiar velocities of galaxies strongly supports the standard model of cosmology where structure forms from gravitational instabilities and galaxies form at the bottom of potential wells.

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Animals’ Wildly Varying Reactions to the Smell of Death

Animals’ Wildly Varying Reactions to the Smell of Death | Amazing Science | Scoop.it

To humans, the scent of a rotting corpse is universally abhorrent, the very definition of disgusting. But as strong as that reaction is, many other animals don’t share our unalloyed revulsion. Goldfish are attracted to the smell. Bengal tigers include it in the cocktail of chemicals used to mark their territory. When a rat catches the smell of death on another of its kind, it will bury the stinky rat—even if it’s not actually dead. Many flies are drawn to the smell of death and deposit their eggs at its source. A type of fungus called stinkhorn uses the scent to lure in flies that pick up the stinkhorn’s spores and carry them far away, a noxious reversal of plants’ use of sweet-smelling nectar.


All of these varied behaviors are in response to the same two chemicals, the evocatively named cadaverine and putrescine, which are formed by the breakdown of proteins in the body of a decaying corpse. Animals’ different reactions are clear signs that they process the chemicals differently, but until the release of a study earlier this month, no one had shown how that processing happens.


The new research focused on zebrafish, an animal often used to study the sense of smell in vertebrates. Despite their evolutionary distance from humans, zebrafish have a similar reaction to cadaverine: They get the heck away. (Presumably this reflects an evolutionary drive in both species to avoid the infectious microbes that congregate in dead bodies.) Researchers from Harvard University and the German Institut für Genetik found a receptor in the olfactory neurons of zebrafish that responds specifically to cadaverine—what science writer Elizabeth Preston calls “a rotten-smell button in the brain.”


What’s perhaps most interesting about the cadaverine receptor is that it is a TAAR, a class of sensors that seems to be important for many animals’ perceptions of disgust, including ours. (See the related Facts So Romantic post, “Misdeeds & Disease: How Similar are Disgust & Moral Disgust?”) One TAAR is responsible for mice’s aversion to the smell of predator pee, while one in our own noses “helps” us smell rotting fish, bad breath, and the odor of bacterially infected vagina. The researchers behind the new study say humans probably don’t have the same receptor as the one in zebrafish, but rather a similar one.


As researchers find more matches between the TAARs and the specific molecules they bind, we should get a better understanding of why some smells revolt us so, and why other animals experience them so differently.

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