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  • richardmitnick 12:17 pm on March 6, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Beamline Comissioning,   

    From BNL: “First Scientific Publication from Data Collected at NSLS-II” 

    Brookhaven Lab

    March 3, 2015
    Chelsea Whyte, (631) 344-8671 or Peter Genzer, (631) 344-3174

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    Just weeks after the National Synchrotron Light Source II (NSLS-II) achieved first light, the team of scientists at the X-Ray Powder Diffraction (XPD) beamline tested a set-up that yielded data on thermoelectric materials. The work was part of the commissioning activities for the XPD beamline, a process that fine-tunes the settings of beamline equipment to ready the facility for first scientific commissioning experiments in mid March on its way to full user operations later in the year. It was published online on March 3 in the scientific journal Applied Physics Letters – Materials. To test the optical performance and components of the beamline, the XPD scientists put a material in the path of the x-ray beam and attempted to characterize its structure as the best way to identify and fix possible flaws or aberrations that the instrument could have caused.

    BNL NSLS-II Interior
    BNL NSLS II Photo
    NSLS-II

    “Our colleagues at NSLS-II were commissioning the XPD beamline and we discussed the best sample for the instrument tuning, something that was going to be straightforward to measure. We realized we could use a sample that was also of scientific interest. It was one of the first things that was put in an NSLS-II beam shortly after the XPD team opened the shutter,” said Simon Billinge, a physicist at Brookhaven National Laboratory who co-authored the paper. “We were lucky. The sample gave valuable information allowing the beam to be tuned, but it also yielded an important scientific result.”

    That result revealed information about the relationship between the atomic structure of ruthenium diselenide (RuSe2) and its thermoelectric properties. Cedomir Petrovic, a condensed matter physicist at Brookhaven National Lab, was inspired to study the diselenide because of its close chemical relationship to iron diantimonide, the material holding the world record for its thermoelectric power factor.

    Thermoelectric materials hold promise for converting waste heat to electricity, as well as for solid-state refrigerators when worked in reverse. Good thermoelectric materials have high power factors and low thermal conductivities. The power factor is a product of thermopower and electrical conductivity. Petrovic reasoned that the little-studied RuSe2 compound would also have a high thermopower – and it did. But it also had a low electrical conductivity, making it less than ideal for real-world applications, and the NSLS-II data showed why.

    When you place a temperature gradient across thermoelectric materials– with one end of the material hotter than the other – electrons at the warm end heat up and gain kinetic energy, eventually migrating toward the cool end. It’s similar to a battery with a positive and negative end; the flow of electrons generates a voltage. The power factor measures how well this happens. If the material also conducts heat well, the cool end will warm up to match the hotter end and the flow will stop. Therefore, a good thermoelectric material has a high power factor but low thermal conductivity.

    Petrovic’s hunch that RuSe2 would have a high thermopower was borne out, but the power factor was limited by the low electrical conductivity. Milinda Abeykoon, who is part of the XPD team carrying out the commissioning, put the sample of this material in the beam to help the team find out why the electrical conductivity was low. The x-rays revealed how the atomic structure of ruthenium diselenide differs from iron antimony. In the latter, picture two pyramids with square bases that share an edge to make up the crystal structure. With ruthenium diselenide, it’s not the bases that share common edges but the vertices, or corners, of these structures that touch. That small change in orientation means there are fewer channels the electrons can flow through, resulting in the low conductivity and the modest power factor, despite the good thermopower.

    “Now that we understand this, we will explore ways to improve the thermoelectric properties of RuSe2, but we will have to concentrate on lowering the thermal conductivity with control over defects and introducing impurities. This will have to be done carefully, though, said Petrovic. “We need to find a way of destroying the thermal conductivity without killing the high thermopower.”

    Billinge adds, “We need a more fundamental understanding of how the thermoelectric properties come about. If we can study more new materials such as RuSe2 that are similar in some ways and different in others, we can tease out, or at least narrow down, what factors give materials their good thermoelectric properties.”

    XPD is designed for in situ and in operando studies of materials, so scientists can explore materials as they function and in real operating conditions. “It took me and my team many years to transform our conceptual ideas into a working state-of-the-art instrument. However, it is a testament to the dedication, effort and planning of the entire NSLS-II team—-from the scientists, engineers, technicians and procurement and administrative staff through the numerous support teams to the specialists overseeing our safety that it all came together so smoothly. There is some magic to see this decade-long process deliver a very intense and stable beam right to the sample so quickly after turning on the machine. There is a real sense of pride here in how well all that work is paying off,” said Eric Dooryhee, who led the design and construction of XPD. “As soon as we could safely stabilize and optimize the x-ray beam in the experimental endstation, we could not wait to benchmark the instrument with a real-world sample and see XPD address its first science case, which promises to be first of a long series.”

    The commissioning data were collected while NSLS-II was operating at just 5 milliamps of ring-current; NSLS-II is designed to provide 100 times more current, and ultrabright coherent x-ray beams.

    “As the power of NSLS-II ramps up, we will eventually put a complete, operating, thermoelectric device in the XPD beam and watch how the structure changes in response to voltage and temperature changes”, said Billinge. That’s what’s going to be possible with the very high brilliance of the beam that we’ll have at NSLS-II when we have the full capability of the machine.”

    Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

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    One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. The Laboratory’s almost 3,000 scientists, engineers, and support staff are joined each year by more than 5,000 visiting researchers from around the world.Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
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  • richardmitnick 3:42 am on March 6, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From NOVA: “Powerful, Promising New Molecule May Snuff Antibiotic Resistant Bacteria” 

    PBS NOVA

    NOVA

    09 Jan 2015
    R.A. Becker

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    Methicillin-resistant staph surround human immune cell.

    Antibiotic resistant bacteria pose one of greatest threats to public health. Without new weapons in our arsenal, these bugs could cause 10 million deaths and cost nearly $100 trillion worldwide each year by the year 2050, according to a recent study commissioned by the British government.

    But just this week, scientists announced that they have discovered a potent new weapon hiding in the ground beneath our feet—a molecule that kills drug resistant bacteria and might itself be resistant to resistance. The team published their results Wednesday in the journal Nature.

    Scientists have been coopting the arsenal of soil-dwelling microorganisms for some time, said Kim Lewis, professor at Northeastern University and senior investigator of the study. Earth-bound bacteria live tightly packed in an intensely competitive environment, which has led to a bacterial arms race. “The ones that can kill their neighbors are going to have an advantage,” Lewis said. “So they go to war with each other with antibiotics, and then we borrow their weapons to fight our own pathogens.”

    However, by the 1960s, the returns from these efforts were dwindling. Not all bacteria that grow in the soil are easy to culture in the lab, and so antibiotic discovery slowed. Lewis attributes this to the interdependence of many soil-dwelling microbes, which makes it difficult to grow only one strain in the lab when it has been separated from its neighbors. “They kill some, and then they depend on some others. It’s very complex, just like in the human community,” he said.

    But a new device called the iChip, developed by Lewis’s team in collaboration with NovoBiotic Pharmaceuticals and colleagues at the University of Bonn, enables researchers to isolate bacteria reluctant to grow in the lab and cultivate them instead where they’re comfortable—in the soil.

    Carl Nathan, chairman of microbiology and immunology at Weill Cornell Medical School and co-author of a recent New England Journal of Medicine commentary about the growing threat of antibiotic resistance, called the team’s discovery “welcome,” adding that it illustrates a point that Lewis has been making for several years, that soil’s well of antibiotic-producing microorganisms “is not tapped out.”

    The researchers began by growing colonies of formerly un-culturable bacteria on their home turf and then evaluating their antimicrobial defenses. They discovered that one bacterium in particular, which they named Eleftheria terrae, makes a molecule known as teixobactin which kills several different kinds of bacteria, including the ones that cause tuberculosis, anthrax, and even drug resistant staph infections.

    Teixobactin isn’t the first promising new antibiotic candidate, but it does have one quality that sets it apart from others. In many cases, even if a new antibiotic is able to kill bacteria resistant to our current roster of drugs, it may eventually succumb to the same resistance that felled its predecessors. (Resistance occurs when the few bacteria strong enough to evade a drug’s killing effects multiply and pass on their genes.)

    Unlike current antibiotic options, though, teixobactin attacks two lipid building blocks of the cell wall, which many bacteria strains can’t live without. By attacking such a key part of the cell, it becomes harder for a bacterium to mutate to escape being killed.

    “This is very hopeful,” Nathan said. “It makes sense that the frequency of resistance would be very low because there’s more than one essential target.” He added, however, that given the many ways in which bacteria can avoid being killed by pharmaceuticals, “Is this drug one against which no resistance will arise? I don’t think that’s actually proved.”

    Teixobactin has not yet been tested in humans. Lewis said the next steps will be to conduct detailed preclinical studies as well as work on improving teixobactin’s molecular structure to solve several practical problems. One they hope to address, for example, is its poor solubility; another is that it isn’t readily absorbed when given orally—as is, it will have to be administered via injection.

    While Lewis predicts that the drug will not be available for at least five years, this new method offers a promising new avenue of drug discovery. Nathan agrees, though he cautions it’s too soon to claim victory. The message of this recent finding, he said, “is not that the problem of antibiotic resistance has been solved and we can stop worrying about it. Instead it’s to say that there’s hope.”

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    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

     
  • richardmitnick 5:36 am on March 5, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From NYT: “Researchers Report Milestone in Developing Quantum Computer” 

    New York Times

    The New York Times

    MARCH 4, 2015
    JOHN MARKOFF

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    This device contains nine qubits, the very unstable basic elements of quantum computing equivalent to bits in a regular computer. In the array, each qubit interacts with its neighbors to protect them from error. Credit Julian Kelly/University of California, Santa Barbara, via Google

    Scientists at the University of California, Santa Barbara, and at Google reported on Wednesday in the journal Nature that they had made a significant advance that brings them a step closer to developing a quantum computer.

    Researchers have been pursuing the development of computers that exploit quantum mechanical effects since the 1990s, because of their potential to vastly expand the performance of conventional computers. The goal has long remained out of reach, however, because the computers are composed of basic elements known as qubits that have remained, despite decades of engineering research, highly unstable.

    In contrast to a bit, which is the basic element of a conventional computer and can represent either a zero or a one, a qubit can exist in a state known as superposition, in which it can represent both a zero and a one simultaneously.

    If the qubits are then placed in an entangled state — physically separate but acting with many other qubits as if connected — they can represent a vast number of values simultaneously.

    To date, matrices of qubits that are simultaneously in superposition and entangled have eluded scientists because they are ephemeral, with the encoded information dissipating within microseconds.

    The university and Google researchers reported, however, that they had succeeded in creating an error-correction system that stabilized a fragile array of nine qubits. The researchers said they had accomplished this by creating circuits in which additional qubits were used to observe the state of the computing qubits without altering their state.

    But an important asterisk remains, according to scientists who read an early version of the paper. The Nature paper stated the researchers had succeeded in preserving only the limited “classical” states, rather than the more complex quantum information that would be needed to create a system that outperforms today’s computers.

    The importance of the advance is that the scientists have developed evidence that the system becomes more stable as they interconnect more qubits in the error-checking array. This suggests that far larger arrays of qubits, composed of thousands or tens of thousands of qubits, might be able to control the errors that have until now bedeviled scientists.

    “We have for the first time in the long history of quantum computing an actual device, where we can test all of our ideas about error detection,” said Rami Barends, a quantum electronics engineer at Google and one of the authors of the paper.

    Julian Kelly, another Google quantum electronics engineer, said there remained significant challenges in manufacturing materials for quantum computing.

    In some cases, the scientists are able to rely on existing semiconductor technology, but there are many steps for which they will have to invent approaches.

    The research was reported by scientists working in the laboratory of John M. Martinis, a physicist at the university. In September, Google announced it would join efforts to build a quantum computer as part of the recently established Quantum Artificial Intelligence Laboratory. Under that agreement, Dr. Martinis joined Google while keeping his teaching role, and members of his laboratory became Google employees.

    While the researchers described their new circuit as a significant advance, they acknowledged that they had not yet solved all of the problems that prevented the building of a working quantum computer.

    “While the basic physical processes behind quantum error correction are feasible, many challenges remain, such as improving the logic operations behind error correction and testing protection from phase-flip errors,” the scientists noted in a statement posted on the company’s website.

    In a discussion of the Nature paper on his website, the M.I.T. physicist Scott Aaronson suggested that the achievement represented about half the progress required to build a fully functional quantum computer.

    Google is not the only computing company collaborating with academic researchers in advancing quantum computing. IBM is working with scientists at Yale, and Microsoft is working separately with researchers at the University of California, Santa Barbara, supporting the Station Q research laboratory it created there in 2006.

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  • richardmitnick 5:02 am on March 5, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Paleoanthropology,   

    From NYT: “Jawbone’s Discovery Fills Barren Evolutionary Period” 

    New York Times

    The New York Times

    MARCH 4, 2015
    JOHN NOBLE WILFORD

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    The Ledi-Geraru mandible fossil. Credit William Kimble/Arizona State University

    On the morning of Jan. 29, 2013, Chalachew Seyoum was climbing a remote hill in the Afar region of his native Ethiopia, his head bent, eyes focused on the loose sediment. The site, known as Ledi-Geraru, was rich in fossils. Soon enough, he spotted a telltale shape on the surface — a premolar, as it turned out. It was attached to a piece of a mandible, or lower jawbone. He collected other pieces of a left mandible, and five teeth in all.

    Mr. Seyoum, a graduate student in paleoanthropology at Arizona State University, had made a discovery that vaulted evolutionary science over a barren stretch of fossil record between two million and three million years ago. This was a time when the human genus, Homo, was getting underway. The 2.8-million-year-old jawbone of a Homo habilis predates by at least 400,000 years any previously known Homo fossils.

    More significant, scientists say, is that this H. habilis lived only 200,000 years after the last known evidence of its more apelike predecessors, Australopithecus afarensis, the species made famous by “Lucy,” whose skeleton was found in the 1970s at the nearby Ethiopian site of Hadar.

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    The fossil of Olduvai Hominid 7, includes a partial lower jaw, bones of the brain case and hand bones. Credit John Reader

    William H. Kimbel, director of the Institute of Human Origins at Arizona State, said the Ledi-Geraru jaw “helps narrow the evolutionary gap between Australopithecus and early Homo,” adding that it was an excellent “transitional fossil in a critical time period in human evolution.”

    The discovery was announced Wednesday in two reports for the journal Science by researchers at Arizona State, the University of Nevada, Las Vegas, and Pennsylvania State University. One paleoanthropologist not on the teams, Fred Spoor of University College London and the Max Planck Institute for Evolutionary Anthropology in Germany, endorsed the analysis.

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    The Ledi-Geraru mandible fossil. Credit William Kimble/Arizona State University

    Dr. Spoor said in an email that he agreed with the hypothesis that the new Ledi-Geraru mandible “derives from Australopithecus afarensis, and at 2.8 million years shows morphology that is ancestral to all early Homo.”

    How could Dr. Spoor not agree with the interpretation of the findings in the new report by Brian A. Villmoare of the University of Nevada, Las Vegas, and colleagues on the Arizona State team? By coincidence, Dr. Spoor was ready to predict many of the findings in the journal Nature a day before his predictions would have been proved right in the journal Science. When the relationship between the studies became clear, the two journals agreed to simultaneous publication of the articles on Wednesday.

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    The hills of the Lee Adoyta region in Ethiopia expose sediments that are less than 2.67 million years old, which helps to date the mandible. Credit Erin DiMaggio/Penn State University

    Dr. Spoor’s predictions were drawn from a digital reconstruction of the disturbed remains of the jaws of the original 1.8-million-year-old Homo habilis specimen found 50 years ago by the legendary fossil hunters Louis and Mary Leakey at Olduvai Gorge in Tanzania.

    The reconstruction, suggesting a plausible evolutionary link between A. afarensis and H. habilis, yielded a remarkably primitive picture of a deep-rooted diversity of a species that emerged much earlier than the 2.3 million years ago suggested by some specimens. The teeth and jaws appeared to be more similar to A. afarensis than to subsequent Homo erectus or Homo sapiens, modern humans that emerged about 200,000 years ago.

    Dr. Spoor’s analysis also seemed to put a new face on H. habilis. He said that individual species of early Homo were more easily recognizable by jaw structure and facial features than by differences in brain size, which tend to be highly variable. Dr. Villmoare and colleagues made similar observations in their article. Both the predictions and the mandible findings called attention to smaller teeth with the emergence of H. habilis and evidence suggesting that the species probably split in different evolutionary lines, only one of which might have been ancestral to later H. erectus and H. sapiens.

    In an email, Dr. Spoor explained that the split occurred sometime before 2.3 million years ago. The lineage leading to H. habilis must have kept the primitive jaw morphology. The Ledi-Geraru specimen kept the primitive, sloping chin that links it to a Lucy-like ancestor. Other lineages must account for the fact that H. erectus and H. habilis existed together for a period more than a million years ago.

    In a second report for the journal Science, Erin N. DiMaggio of Penn State and other geologists examined soil, vegetation and fossils at Ledi-Geraru. They determined that when the H. habilis left its jaw there, the habitat was dominated by mammals that lived in a more open landscape — grasslands and low shrubs — than the more wooded land often favored by A. afarensis.

    But after about 2.8 million years ago, increased African aridity has been cited as a possible result of widespread climate change affecting species changes and extinctions. Kaye E. Reed, co-leader of the Arizona State team, noted that the “aridity signal” had been observed at the Ethiopian fossil site. However, she said, “it’s still too soon to say this means climate change is responsible for the origin of Homo.”

    For that, Dr. Reed said, “we need a larger sample of hominin fossils, and that’s why we continued to come to the Ledi-Geraru area to search.” That, and to learn more about the evolution of our genus, Homo.

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  • richardmitnick 6:18 pm on March 4, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From CMU: “Intermediary Neuron Acts as Synaptic Cloaking Device, Says Carnegie Mellon Study” 

    Carnegie Mellon University logo
    Carnegie Mellon university

    February 26, 2015
    Jocelyn Duffy / 412-268-9982

    1

    Neuroscientists believe that the connectome, a map of each and every connection between the millions of neurons in the brain, will provide a blueprint that will allow them to link brain anatomy to brain function. But a new study from Carnegie Mellon University has found that a specific type of neuron might be thwarting their efforts at mapping the connectome by temporarily cloaking the synapses that link a wide field of neurons.

    If you’re a Star Trek fan, think of it as a Romulan or Klingon cloaking device, which hides a warship. The cloaked ship is invisible, until it fires at an enemy. In the study published in the March 16 issue of Current Biology, the researchers found that a class of inhibitory neurons, called somatostatin cells, send out a signal — much like a cloaking device — that silences neighboring excitatory neurons. Synapses, like a cloaked warship, can’t be seen if they aren’t firing; activating the somatostatin cells makes the synapses and local network of neurons invisible to researchers.

    Furthermore, by silencing certain parts of the neuronal network, the activity of the somatostatin neurons also can change the way the brain functions, heightening some perceptual pathways and silencing others.

    “It was totally unexpected that these cells would work this way,” said Alison Barth, professor of biological sciences and a member of BrainHubSM, Carnegie Mellon’s neuroscience research initiative. “Changing the activity of just this one cell type can let you change the brain’s circuit structure at will. This could dramatically change how we look at — and use — the connectome.”

    The Carnegie Mellon researchers discovered this synaptic cloaking device, much in the same way Starfleet would detect a cloaked Klingon warship — they were conducting their normal research and noticed that something just didn’t look quite right.

    Joanna Urban-Ciecko, a research scientist in Barth’s lab, noticed that the synapses in her experiments were not behaving the way that previous experimenters had reported. Prior studies reported that the synapses should be strong and reliable, and that they should always grow and strengthen in response to a stimulus. But the neurons Urban-Ciecko looked at were weak and unreliable.

    The difference between Urban-Ciecko’s research and the previously completed work was that her research was being done under real-life conditions. Prior research on synapse function was done under conditions optimized for observing synapses. However, such experimental conditions don’t reflect the noisy brain environment in which synapses normally exist.

    “There’s this big black box in neuroscience. We know how to make synapses stronger in a dish. But what’s going on in the brain to initiate synaptic strengthening in real life?” Barth asked.

    To find out, Urban-Ciecko looked at neurons in the brain’s neocortex that were functioning under normal, noisy conditions. She took paired-cell recordings from pyramidal cells, a type of excitatory neuron, and found that many of the synapses between the neurons were not functioning, or functioning at an unexpectedly low level. Urban-Ciecko then recorded the activity of somatostatin cells, a type of inhibitory neuron, and found that those neurons were much more active than expected.

    “The somatostatin cells were so active, I wondered if they could possibly be driving the inhibition of synapses,” Urban-Ciecko said.

    To test her hypothesis, Urban-Ciecko turned to optogenetics, a technique that controls neurons with light. She used light to trigger an enzyme that activated and deactivated the somatostatin neuron. When the somatostatin cells were turned off, synapses grew big and strong. When the cells were turned on, the synapses became weaker and in some cases, disappeared entirely.

    “You have inputs coming at you all the time, why do you remember one thing and not the other? We think that somatostatin neurons may be gating whether synapses are used, and whether they can be changed during some important event, to enable learning,” said Barth, who is also a member of the joint CMU/University of Pittsburgh Center for the Neural Basis of Cognition (CNBC).

    The researchers found that when the somatostatin neurons were turned on, this triggered the cloaking device. The neuron activated the GABAb receptors on hundreds of excitatory neurons in the immediate area. Activating this receptor suppressed the excitatory neurons, which prevented them from creating and strengthening synapses — and made them invisible to researchers.

    The researchers next plan to see if the somatostatin cells behave similarly in other areas of the brain. If they do, it could represent a novel target for studying and improving learning and memory.

    Erika E. Fanselow, a research biologist formerly with Carnegie Mellon and the CNBC, also contributed to this paper.
    The research was funded by the McKnight Foundation and the National Institutes of Health (DA0171-88).

    As the birthplace of artificial intelligence and cognitive psychology, Carnegie Mellon has been a leader in the study of brain and behavior for more than 50 years. The university has created some of the first cognitive tutors, helped to develop the Jeopardy-winning Watson, founded a groundbreaking doctoral program in neural computation, and completed cutting-edge work in understanding the genetics of autism. Building on its strengths in biology, computer science, psychology, statistics and engineering, CMU recently launched BrainHubSM, a global initiative that focuses on how the structure and activity of the brain give rise to complex behaviors.

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    Carnegie Mellon Campus

    Carnegie Mellon University (CMU) is a global research university with more than 12,000 students, 95,000 alumni, and 5,000 faculty and staff.
    CMU has been a birthplace of innovation since its founding in 1900.
    Today, we are a global leader bringing groundbreaking ideas to market and creating successful startup businesses.
    Our award-winning faculty members are renowned for working closely with students to solve major scientific, technological and societal challenges. We put a strong emphasis on creating things—from art to robots. Our students are recruited by some of the world’s most innovative companies.
    We have campuses in Pittsburgh, Qatar and Silicon Valley, and degree-granting programs around the world, including Africa, Asia, Australia, Europe and Latin America.

     
  • richardmitnick 7:51 pm on March 3, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , , WYSS Institute   

    From Wyss Institute at Harvard: “Activating genes on demand” 

    Harvard University

    Harvard University

    Harvard Wyss Institute

    Mar 3, 2015
    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Kat J. McAlpine, katherine.mcalpine@wyss.harvard.edu, +1 617-432-8266

    Harvard Medical School
    David Cameron, david_cameron@hms.harvard.edu, +1 617-432-0441

    New mechanism for engineering genetic traits governed by multiple genes paves the way for various advances in genomics and regenerative medicine

    When it comes to gene expression – the process by which our DNA provides the recipe used to direct the synthesis of proteins and other molecules that we need for development and survival – scientists have so far studied one single gene at a time. A new approach developed by Harvard geneticist George Church, Ph.D., can help uncover how tandem gene circuits dictate life processes, such as the healthy development of tissue or the triggering of a particular disease, and can also be used for directing precision stem cell differentiation for regenerative medicine and growing organ transplants.

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    In these images, the ability of the new Cas9 approach to differentiate stem cells into brain neuron cells is visible. On the left, a previous attempt to direct stem cells to develop into neuronal cells shows a low level of success, with limited red–colored areas indicating low growth of neuron cells. On the right, the new Cas9 approach shows a 40–fold increase in the number of neuronal cells developed, visible as red-colored areas on the image. Credit: Wyss Institute at Harvard University

    The findings, reported by Church and his team of researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School in Nature Methods, show promise that precision gene therapies could be developed to prevent and treat disease on a highly customizable, personalized level, which is crucial given the fact that diseases develop among diverse pathways among genetically–varied individuals.

    The approach leverages the Cas9 protein, which has already been employed as a Swiss Army knife for genome engineering, in a novel way. The Cas9 protein can be programmed to bind and cleave any desired section of DNA – but now Church’s new approach activates the genes Cas9 binds to rather than cleaving them, triggering them to activate transcription to express or repress desired genetic traits. And by engineering the Cas9 to be fused to a triple–pronged transcription factor, Church and his team can robustly manipulate single or multiple genes to control gene expression.

    “In terms of genetic engineering, the more knobs you can twist to exert control over the expression of genetic traits, the better,” said Church, a Wyss Core Faculty member who is also Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. “This new work represents a major, entirely new class of knobs that we could use to control multiple genes and therefore influence whether or not specific genetics traits are expressed and to what extent – we could essentially dial gene expression up or down with great precision.”

    Such a capability could lead to gene therapies that would mitigate age–related degeneration and the onset of disease; in the study, Church and his team demonstrated the ability to manipulate gene expression in yeast, flies, mouse and human cell cultures.

    “We envision using this approach to investigate and create comprehensive libraries that document which gene circuits control a wide range of gene expression,” said one of the study’s lead authors Alejandro Chavez, Ph.D., Postdoctoral Fellow at the Wyss Institute. Jonathan Schieman, Ph.D, of the Wyss Institute and Harvard Medical School, and Suhani Vora, of the Wyss Institute, Massachusetts Institute of Technology, and Harvard Medical School, are also lead co–authors on the study.

    In this technical animation, Wyss Institute researchers instruct how they engineered a Cas9 protein to create a powerful and robust tool for activating gene expression. The novel method enables Cas9 to switch a gene from off to on and has the potential to precisely induce on-command expression of any of the countless genes in the genomes of yeast, flies, mice, or humans. Credit: Wyss Institute at Harvard University

    The new Cas9 approach could also potentially target and activate sections of the genome made up of genes that are not directly responsible for transcription, and which previously were poorly understood. These sections, which comprise up to 90% of the genome in humans, have previously been considered to be useless DNA “dark matter” by geneticists. In contrast to translated DNA, which contains recipes of genetic information used to express traits, this DNA dark matter contains transcribed genes which act in mysterious ways, with several of these genes often having influence in tandem.

    But now, that DNA dark matter could be accessed using Cas9, allowing scientists to document which non-translated genes can be activated in tandem to influence gene expression. Furthermore, these non-translated genes could also be turned into a docking station of sorts. By using Cas9 to target and bind gene circuits to these sections, scientists could introduce synthetic loops of genes to a genome, therefore triggering entirely new or altered gene expressions.

    The ability to manipulate multiple genes in tandem so precisely also has big implications for advancing stem cell engineering for development of transplant organs and regenerative therapies.

    “In order to grow organs from stem cells, our understanding of developmental biology needs to increase rapidly,” said Church. “This multivariate approach allows us to quickly churn through and analyze large numbers of gene combinations to identify developmental pathways much faster than has been previously capable.”

    To demonstrate this point, the researchers used it to grow brain neuron cells from stem cells and found that using the approach to program development of neuronal cells was 40–fold more successful than prior established methods. This is the first time that Cas9 has been leveraged to efficiently differentiate stem cells into brain cells.

    The new approach is also compatible to be used in combination with other gene editing technologies. Church and his team have previously made breakthroughs by developing a gene editing mechanism for therapeutic applications and gene drives for altering traits in plant and animal species.

    “This newest tool in the Cas9 genome engineering arsenal offers a powerful new way to control cell and tissue function that could revolutionize virtually all areas of science and medicine, ranging from gene therapy to regenerative medicine and anti–aging,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital and Professor of Bioengineering at Harvard SEAS.

    See the full article here.

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

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  • richardmitnick 12:27 pm on March 3, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , , LBL ALS   

    From LBL: “A New Level of Earthquake Understanding” 

    Berkeley Logo

    Berkeley Lab

    March 3, 2015
    Lynn Yarris

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    The notorious San Andreas Fault runs virtually the entire length of California

    As everyone who lives in the San Francisco Bay Area knows, the Earth moves under our feet. But what about the stresses that cause earthquakes? How much is known about them? Until now, our understanding of these stresses has been based on macroscopic approximations. Now, the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) is reporting the successful study of stress fields along the San Andreas fault at the microscopic scale, the scale at which earthquake-triggering stresses originate.

    Working with a powerful microfocused X-ray beam at Berkeley Lab’s Advanced Light Source (ALS), a DOE Office of Science User Facility, researchers applied Laue X-ray microdiffraction, a technique commonly used to map stresses in electronic chips and other microscopic materials, to study a rock sample extracted from the San Andreas Fault Observatory at Depth (SAFOD). The results could one day lead to a better understanding of earthquake events.

    “Stresses released during an earthquake are related to the strength of rocks and thus in turn to the rupture mechanism,” says Martin Kunz, a beamline scientist with the ALS’s Experimental Systems Group. “We found that the distribution of stresses in our sample were very heterogeneous at the micron scale and much higher than what has been reported with macroscopic approximations. This suggests there are different processes at work at the microscopic and macroscopic scales.”

    Kunz is one of the co-authors of a paper describing this research in the journal Geology. The paper is titled Residual stress preserved in quartz from the San Andreas Fault Observatory at Depth. Co-authors are Kai Chen, Nobumichi Tamura and Hans-Rudolf Wenk.

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    (From left) Hans Wenk, Nobumichi Tamura and Martin Kunz at ALS beamline 12.3.2 where they applied Laue X-ray microdiffraction to study quartz from the San Andreas Fault. (Photo by Roy Kaltschmidt)

    Most earthquakes occur when stress that builds up in rocks along active faults, such as the San Andreas, is suddenly released, sending out seismic waves that make the ground shake. The pent- up stress results from the friction caused by tectonic forces that push two plates of rock against one another.

    “In an effort to better understand earthquake mechanisms, several deep drilling projects have been undertaken to retrieve material from seismically active zones of major faults such as SAFOD,” says co-author Wenk, a geology professor with the University of California (UC) Berkeley’s Department of Earth and Planetary Science and the leading scientist of this study. “These drill-core samples can be studied in the laboratory for direct information about physical and chemical processes that occur at depth within a seismically active zone. The data can then be compared with information about seismicity to advance our understanding of the mechanisms of brittle failure in the Earth’s crust from microscopic to macroscopic scales.”

    Kunz, Wenk and their colleagues measured remnant or “fossilized” stress fields in fractured quartz crystals from a sample taken out of a borehole in the San Andreas Fault near Parkfield, California at a depth of 2.7 kilometers. The measurements were made using X-ray Laue microdiffraction, a technique that can determine elastic deformation with a high degree of accuracy. Since minerals get deformed by the tectonic forces that act on them during earthquakes, measuring elastic deformation reveals how much stress acted on the minerals during the quake.

    “Laue microdiffraction has been around for quite some time and has been exploited by the materials science community to quantify elastic and plastic deformation in metals and ceramics, but has been so far only scarcely applied to geological samples”, says co-author Tamura, a staff scientist with the ALS’s Experimental Systems Group who spearheads the Laue diffraction program at the ALS.

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    Using ALS beamline 12.3.2, researchers carried out an X-ray microdiffraction study on quartz grains from the San Andreas Fault Observatory at Depth and found a heterogeneous distribution of stress.

    The measurements were obtained at ALS beamline 12.3.2, a hard (high-energy) X-ray diffraction beamline specialized for Laue X-ray microdiffraction.

    “ALS Beamline 12.3.2 is one of just a few synchrotron-based X-ray beamlines in the world that can be used to measure residual stresses using Laue micro diffraction,” Tamura says.

    In their analysis, the Berkeley researchers found that while some of the areas within individual quartz fragments showed no elastic deformation, others were subjected to stresses in excess of 200 million pascals (about 30,000 psi). This is much higher than the tens of millions of pascals of stress reported in previous indirect strength measurements of SAFOD rocks.

    “Although there are a variety of possible origins of the measured stresses, we think these measured stresses are records of seismic events shocking the rock”, says co-author Chen of China’s Xi’an Jiantong University. It is the only mechanism consistent with the geological setting and microscopic observations of the rock.”

    The authors believe their Laue X-ray microdiffraction technique has great potential for measuring the magnitude and orientation of residual stresses in rocks, and that with this technique quartz can serve as “paleo-piezometer” for a variety of geological settings and different rock types.

    “Understanding the stress fields under which different types of rock fail will help us better understand what triggers earthquakes,” says Kunz. “Our study could mark the beginning of a whole new era of quantifying the forces that shape the Earth.”

    This research was supported by the DOE Office of Science.

    See the full article here.

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    A U.S. Department of Energy National Laboratory Operated by the University of California

    University of California Seal

    DOE Seal

     
  • richardmitnick 1:48 pm on March 1, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From Perimeter: “Pioneering Women of Physics” 

    Perimeter Institute
    Perimeter Institute

    February 25, 2015

    For more information, contact:
    Lisa Lambert
    Manager, External Relations and Public Affairs
    llambert@perimeterinstitute.ca
    (519) 569-7600 x5051

    They discovered pulsars, found the first evidence of dark matter, pioneered mathematics, radioactivity, nuclear fission, elasticity, and computer programming, and have even stopped light.
    Perimeter celebrates women who made pioneering contributions to physics, often overcoming tremendous challenges to do so.

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    See the full article here.

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    About Perimeter

    Perimeter Institute is a leading centre for scientific research, training and educational outreach in foundational theoretical physics. Founded in 1999 in Waterloo, Ontario, Canada, its mission is to advance our understanding of the universe at the most fundamental level, stimulating the breakthroughs that could transform our future. Perimeter also trains the next generation of physicists through innovative programs, and shares the excitement and wonder of science with students, teachers and the general public.

     
  • richardmitnick 1:19 pm on March 1, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From NASA Earth: “Bang Kachao: Bangkok’s Green Lung” 

    NASA Earth Observatory

    NASA Earth Observatory

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    acquired February 2, 2014
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    acquired February 2, 2014

    In the heart of Thailand’s most populous city, an oasis stands out from the urban landscape like a great “green lung.” That’s the nickname given to Bang Kachao—a lush protected area that has escaped the dense development seen elsewhere in Bangkok.

    The city is built on the alluvial plain of the Chao Phraya River. Toward the southern end, near the Gulf of Thailand, is an old meander that never quite formed an oxbow lake. That meander traces the boundary of Bang Kachao, which TIME magazine once called the “best urban oasis” in Asia.

    On February 2, 2014, the Operational Land Imager (OLI) on Landsat 8 captured this natural-color view of Bang Kachao (also called Bang Krachao or Bang Kra Jao). The top image is a close up view of the region outlined with a rectangle in the bottom image.

    NASA LandSat8 OLI
    OLI

    NASA LandSat 8
    Landsat 8

    Bang Kachao is actually an island—albeit an artificial one. The Klong Lad Pho canal, built at the neck of the oxbow, allows water from the Chao Phraya to more quickly reach the sea. The canal contains floodgates that control water levels to prevent flooding. Immediately west of the canal is the Bhumibol Bridge, which twice crosses the Chao Phraya River.

    Look east of the mid-bridge interchange, however, and a stark transition occurs, as the urban jungle gives way to about 2,000 hectares of rural jungle, villages, and farmland. According to a travel story in The New York Times, Bang Kachao is gaining popularity among tourists lured by bike tours, a floating farmers’ market, and the relaxed atmosphere.

    See the full article here.

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    The Earth Observatory’s mission is to share with the public the images, stories, and discoveries about climate and the environment that emerge from NASA research, including its satellite missions, in-the-field research, and climate models. The Earth Observatory staff is supported by the Climate and Radiation Laboratory, and the Hydrospheric and Biospheric Sciences Laboratory located at NASA Goddard Space Flight Center.

     
  • richardmitnick 5:11 pm on February 27, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From The Siberian Times: “Concerns over future of joint Russian-American weather station” 

    Siberian Times

    The Siberian Times

    27 February 2015
    Olga Gertcyk

    Built just five years ago, western sanctions over Ukraine stop international cooperation at climate change research facility in Arctic.

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    Opened less than five years ago in Tiksi, in the Russian Far East, observatory was the first major polar weather station to be built through such multi-national cooperation. Picture: Maxim Avdeev/Forbes

    The future of a climate change monitoring facility in the Arctic run jointly by Russia and the United States is under threat following tensions between the nations.

    The Hydrometeorological Observatory was developed through a partnership between the National Science Foundation (NSF) and National Oceanic and Atmospheric Administration (NOAA) in America, the Finnish Meteorological Institute, and the Russian Federal Service for Hydrometeorology and Environmental Monitoring (Roshydromet).

    Opened less than five years ago in Tiksi, in the Russian Far East, it was the first major polar weather station to be built through such multi-national cooperation. It was installed with state-of-the-art equipment to take long-term environmental measurements, with the data made freely available to the international community.

    But with sanctions between the West and Russia following the Ukraine crisis, the future of the facility is now in question.

    All activity between nations at the observatory has been suspended after a decree by the US State Department banning any cooperation with Russian scientists on climate research.

    ‘There are difficulties in the relationships with the partners, first of all with the United States,’ said Alexander Frolov, the head of Roshydromet. ‘Officially, the State Department has banned cooperation on climate for government agencies such as NOAA with Roshydromet.

    ‘We are experiencing certain problems in this regard, since we had very good relations. The specialists from the United States are not experiencing any less problems because Tiksi is our very successful joint project.’

    He added: ‘I was approached by the president of the World Meteorological Organization. He is Canadian. I told him, ‘remove the sanctions and you get data’.’

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    It was built with a 20metre-high tower, air sampling stacks and boardwalks to maintain the pristine environment, and it aims to keep track of weather patterns, atmospheric differences, and changes to the thickness of the ice and permafrost. Pictures: NOAA

    The new observatory was opened in August 2010 to compliment the facilities already in existence in the Arctic region to monitor climate change.

    Tiksi is one of the most northern settlements in Yakutia, also known as the Sakha Republic, and was established in 1933 as one of the points on the Northern Sea Route. Since 1957, the Polar Geo-cosmic Observatory has been operational there.

    According to Interfax, the US State Department ban led to the suspension of the American scientists’ work on atmospheric observatory.

    Now Russian staff left at the facility are uncertain as to what the future might hold. While they are not working directly with the Americans, data is still being collected and passed to the Arctic and Antarctic Research Institute in St Petersburg and then on to foreign fellow researchers, including those at the NOAA.

    Yury Dikhtyarenko, deputy head of Yakut Hydromet Service, said: ‘We haven’t yet received any decrees from Roshydromet so at the moment I can’t say how it will affect the partnership.’

    Galina Chumachenko, head of Tiksi branch of the Yakut Hydromet Service, said: ‘We will keep sharing the data with scientists until we get official information. In the event a prohibition is launched, then the information from St Petersburg won’t be passed, and that’s it.’

    According to Chumachenko, it won’t affect meteorological forecasts because the American equipment is very particular and is mainly registering information on emissions and their concentration in the atmosphere.

    She doubts the equipment will be taken away. ‘First, it would be a very pricey procedure,’ she stressed. ‘Second, I think that the fellow American researchers are smart enough and won’t do that after five years of partnership.’

    There are about 870 climatic and atmospheric measuring stations in the world, of which 113 are Russian.

    See the full article here.

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