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  • richardmitnick 2:07 pm on February 10, 2016 Permalink | Reply
    Tags: Applied Research & Technology, Biomolecules, , , ,   

    From DESY: “New method opens crystal clear views of biomolecules” 


    No writer credit found

    A scientific breakthrough gives researchers access to the blueprint of thousands of molecules of great relevance to medicine and biology. The novel technique, pioneered by a team led by DESY scientist Professor Henry Chapman from the Center for Free-Electron Laser Science CFEL and reported this week in the scientific journal Nature, opens up an easy way to determine the spatial structures of proteins and other molecules, many of which are practically inaccessible by existing methods. The structures of biomolecules reveal their modes of action and give insights into the workings of the machinery of life. Obtaining the molecular structure of particular proteins, for example, can provide the basis for the development of tailor-made drugs against many diseases. “Our discovery will allow us to directly view large protein complexes in atomic detail,” says Chapman, who is also a professor at the University of Hamburg and a member of the Hamburg Centre for Ultrafast Imaging CUI.

    Dimer crystals Detec of complex biomolecules like that of the photosystem II molecule shown here
    Slightly disordered crystals of complex biomolecules like that of the photosystem II molecule shown here produce a complex continous diffraction pattern (right, the disorder is greatly exaggerated) under X-ray light that contains far more information than the so-called Bragg peaks of a strongly ordered crystal alone (left). Credit: DESY, Eberhard Reimann

    To determine the spatial structure of a biomolecule, scientists mainly rely on a technique called crystallography. The new work offers a direct route to “read” the atomic structure of complex biomolecules by crystallography without the usual need for prior knowledge and chemical insight. “This discovery has the potential to become a true revolution for the crystallography of complex matter,” says the chairman of DESY’s board of directors, Professor Helmut Dosch.

    In crystallography, the structure of a crystal and of its constituents can be investigated by shining X-rays on it. The X-rays scatter from the crystal in many different directions, producing an intricate and characteristic pattern of numerous bright spots, called Bragg peaks (named after the British crystallography pioneers William Henry and William Lawrence Bragg). The positions and strengths of these spots contain information about the structure of the crystal and of its constituents. Using this approach, researchers have already determined the atomic structures of tens of thousands of proteins and other biomolecules.

    But the method suffers from two significant barriers, which make structure determination extremely difficult or sometimes impossible. The first is that the molecules must be formed into very high quality crystals. Most biomolecules do not naturally form crystals. However, without the necessary perfect, regular arrangement of the molecules in the crystal, only a limited number of Bragg peaks are visible. This means the structure cannot be determined, or at best only a fuzzy “low resolution” facsimile of the molecule can be found. This barrier is most severe for large protein complexes such as membrane proteins. These systems participate in a range of biological processes and many are the targets of today’s drugs. Great skill and quite some luck are needed to obtain high-quality crystals of them.

    Extreme Sudoku in three dimensions

    The second barrier is that the structure of a complex molecule is still extremely difficult to determine, even when good diffraction is available. “This task is like extreme Sudoku in three dimensions and a million boxes, but with only half the necessary clues,” explains Chapman. In crystallography, this puzzle is referred to as the phase problem. Without knowing the phase – the lag of the crests of one diffracted wave to another – it is not possible to compute an image of the molecule from the measured diffraction pattern. But phases can’t be measured. To solve the tricky phase puzzle, more information must be known than just the measured Bragg peaks. This additional information can sometimes be obtained by X-raying crystals of chemically modified molecules, or by already knowing the structure of a closely-related molecule.

    When thinking about why protein crystals do not always “diffract”, Chapman realised that imperfect crystals and the phase problem are linked. The key lies in a weak “continuous” scattering that arises when crystals become disordered. Usually, this non-Bragg, continuous diffraction is thought of as a nuisance, although it can be useful for providing insights into vibrations and dynamics of molecules. But when the disorder consists only of displacements of the individual molecules from their ideal positions in the crystal then the “background” takes on a much more complex character – and its rich structure is anything but diffuse. It then offers a much bigger prize than the analysis of the Bragg peaks: the continuously-modulated “background” fully encodes the diffracted waves from individual “single” molecules.

    “If you would shoot X-rays on a single molecule, it would produce a continuous diffraction pattern free of any Bragg spots,” explains lead author Dr. Kartik Ayyer from Chapman’s CFEL group at DESY. “The pattern would be extremely weak, however, and very difficult to measure. But the ‘background’ in our crystal analysis is like accumulating many shots from individually-aligned single molecules. We essentially just use the crystal as a way to get a lot of single molecules, aligned in common orientations, into the beam.” With imperfect, disordered crystals, the continuous diffraction fills in the gaps and beyond the Bragg peaks, giving vastly more information than in normal crystallography. With this additional gain in information, the phase problem can be uniquely solved without having to resort to other measurements or assumptions. In the analogy of the Sudoku puzzle, the measurements provide enough clues to always arrive at the right answer.

    The best crystals are imperfect crystals

    This novel concept leads to a paradigm shift in crystallography — the most ordered crystals are no longer the best to analyse with the novel method. Instead, the best crystals are imperfect crystals. “For the first time we have access to single molecule diffraction – we have never had this in crystallography before,” he explains. “But we have long known how to solve single-molecule diffraction if we could measure it.” The field of coherent diffractive imaging, spurred by the availability of laser-like beams from X-ray free-electron lasers, has developed powerful algorithms to directly solve the phase problem in this case, without having to know anything at all about the molecule. “You don’t even have to know chemistry,” says Chapman, “but you can learn it by looking at the three-dimensional image you get.”

    To demonstrate their novel analysis method, the Chapman group teamed up with the group of Professor Petra Fromme from the Arizona State University (ASU), and other colleagues from ASU, University of Wisconsin, the Greek Foundation for Research and Technology – Hellas FORTH, and SLAC National Accelerator Laboratory in the U.S. They used the world’s most powerful X-ray laser LCLS at SLAC to X-ray imperfect microcrystals of a membrane protein complex called Photosystem II that is part of the photosynthesis machinery in plants.

    SLAC LCLS Inside
    Inside LCLS

    Including the continuous diffraction pattern into the analysis immediately improved the spatial resolution around a quarter from 4.5 Ångström to 3.5 Ångström (an Ångström is 0.1 nanometres). The obtained image gave fine definition of molecular features that usually require fitting a chemical model to see. “That is a pretty big deal for biomolecules,” explains co-author Dr. Anton Barty from DESY. “And we can further improve the resolution if we take more patterns.” The team had only a few hours of measuring time for these experiments, while full-scale measuring campaigns usually last a couple of days.

    The scientists hope to obtain even clearer and higher resolution images of photosystem II and many other macromolecules with their new technique. “This kind of continuous diffraction has actually been seen for a long time from many different poorly-diffracting crystals,” says Chapman. “It wasn’t understood that you can get structural information from it and so analysis techniques suppressed it. We’re going to be busy to see if we can solve structures of molecules from old discarded data.”

    Macromolecular diffractive imaging using imperfect crystals; Kartik Ayyer et al.; Nature (2016); DOI: 10.1038/nature16949

    See the full article here .

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    DESY is one of the world’s leading accelerator centres. Researchers use the large-scale facilities at DESY to explore the microcosm in all its variety – from the interactions of tiny elementary particles and the behaviour of new types of nanomaterials to biomolecular processes that are essential to life. The accelerators and detectors that DESY develops and builds are unique research tools. The facilities generate the world’s most intense X-ray light, accelerate particles to record energies and open completely new windows onto the universe. 
That makes DESY not only a magnet for more than 3000 guest researchers from over 40 countries every year, but also a coveted partner for national and international cooperations. Committed young researchers find an exciting interdisciplinary setting at DESY. The research centre offers specialized training for a large number of professions. DESY cooperates with industry and business to promote new technologies that will benefit society and encourage innovations. This also benefits the metropolitan regions of the two DESY locations, Hamburg and Zeuthen near Berlin.

  • richardmitnick 1:47 pm on February 8, 2016 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From UC Riverside: “Double Dose of Bad Earthquake News” 

    UC Riverside bloc

    UC Riverside

    February 8, 2016
    Sean Nealon

    A team of researchers, including one from the University of California, Riverside, has discovered that earthquake ruptures can jump much further than previously thought, a finding that could have severe implications on the Los Angeles area and other regions in the world.

    The scientists found that an earthquake that initiates on one thrust fault can spread 10 times farther than previously thought to a second nearby thrust fault, vastly expanding the possible range of “earthquake doublets,” or double earthquakes.

    That could mean in areas such as Los Angeles, where there are multiple thrust faults close to each other, an earthquake from one thrust fault could spread to another fault, creating twice as much devastation.

    One potential bad scenario involves a single earthquake spreading between the Puente Hills thrust fault, which runs under downtown Los Angeles, and the Sierra Madre thrust fault, located close to Pasadena, said Gareth Funning, an associate professor of earth sciences at UC Riverside, and a co-author of a paper published online today (Feb. 8) about the research in the journal Nature Geoscience.

    Other susceptible areas where there are multiple thrust faults are in close proximity include the Ventura, Calif. area, the Middle East, particularly Tehran, Iran, and the front of the Himalayas, in countries such as Afghanistan, Pakistan, India and Nepal.

    Interferogram of earthquakes
    Satellite radar interferograms showing how the ground was moved in the 1997 Pakistan earthquake.

    The researchers studied a 1997 earthquake in Pakistan, originally reported as a magnitude 7.1 event, showing that it was in fact composed of two ‘subevents’ – a magnitude 7.0 earthquake, that was followed 19 seconds later by a magnitude 6.8 event, located 50 kilometers (30 miles) to the southeast.

    Funning considers the two earthquakes as subevents of one ‘mainshock,’ as opposed to the second earthquake being an aftershock, because they happened so close together in time and were so similar in size. There were many aftershocks in the following minutes and hours, but most of them were much smaller.

    The scientists used satellite radar images, precise earthquake locations, modeling and back projection of seismic radiation to prove the seismic waves from the first subevent caused the second to initiate, effectively ‘jumping’ the 50 kilometer distance between the two. Scientists previously thought an earthquake could only leap up to five kilometers.

    The finding has implications for seismic hazard forecasts developed by the United States Geological Survey. The current forecast model does not include the possibility of a similar double earthquake on the thrust faults in the Los Angeles area.

    “This is another thing to worry about,” Funning said. “The probability of this happening in Los Angeles is probably pretty low, but it doesn’t mean it can’t happen.”

    Funning started work on the paper about 12 years ago as a graduate student at the University of Oxford. He was the first to find the satellite data for the earthquakes in Pakistan, which occurred in a largely unpopulated area, and notice they occurred close together in space and time.

    After dropping the work for several years, he, along with lead author Ed Nissen of the Colorado School of Mines, picked it up about three to four years ago, in part because of the possible implications for the Los Angeles area, which has a similar plate boundary, with similar faults, similar distances apart as the region in Pakistan where the 1997 earthquake doublet occurred.

    Thrust faults happen when one layer of rock is pushed up over another, often older, layer of rock by compressional forces. Thrust faults came to the attention of Californians after the 1994 Northridge earthquake, about 20 miles northwest of Los Angeles, which occurred on a thrust fault.

    Thrust faults are not as well understood by scientists as strike-slip faults, such as the San Andreas, in part because they are not as visible in the landscape, and do not preserve evidence for past earthquakes as well.

    The paper is called Limitations of rupture forecasting exposed by instantaneously triggered earthquake doublet. Other authors are: John Elliott and Barry Parsons, both of the University of Oxford; Alastair Sloan, University of Oxford and University of Cape Town; Tim Craig and Tim Wright, both of the University of Leeds; and Alex Hutko, of the Incorporated Research Institutions for Seismology (IRIS) Data Management Center.

    See the full article here .

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    UC Riverside Campus

    The University of California, Riverside is one of 10 universities within the prestigious University of California system, and the only UC located in Inland Southern California.

    Widely recognized as one of the most ethnically diverse research universities in the nation, UCR’s current enrollment is more than 21,000 students, with a goal of 25,000 students by 2020. The campus is in the midst of a tremendous growth spurt with new and remodeled facilities coming on-line on a regular basis.

    We are located approximately 50 miles east of downtown Los Angeles. UCR is also within easy driving distance of dozens of major cultural and recreational sites, as well as desert, mountain and coastal destinations.

  • richardmitnick 1:28 pm on February 8, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , , , Sea level rise and global warming   

    From LLNL: “Consequences of today’s carbon emissions will linger for thousands of years, study finds” 

    Lawrence Livermore National Laboratory

    Feb. 8, 2016
    Anne M Stark

    Carbon emissions
    Carbon emissions in carbon dioxide

    The Earth may suffer irreversible damage that could last tens of thousands of years because of the rate humans are emitting carbon into the atmosphere.

    In a new study in Nature Climate Change, researchers at Oregon State University, Lawrence Livermore National Laboratory and collaborating institutions found that the longer-term impacts of climate change go well past the 21st century.

    “Much of the carbon we are putting in the air from burning fossil fuels will stay there for thousands of years — and some of it will be there for more than 100,000 years,” said Peter Clark, an Oregon State University paleoclimatologist and lead author on the article. “People need to understand that the effects of climate change on the planet won’t go away, at least not for thousands of generations.”

    LLNL’s Benjamin Santer said the focus on climate change at the end of the 21st century needs to be shifted toward a much longer-term perspective.

    “Our greenhouse gas emissions today produce climate-change commitments for many centuries to come,” Santer said. “Today’s actions — or inaction — will have long-term climate consequences for generations of our descendants.”

    “The long-term view sends the chilling message what the real risks and consequences are of the fossil fuel era,” said Thomas Stocker of the University of Bern in Switzerland, who is past co-chair of the Intergovernmental Panel on Climate Change’s (IPCC) Working Group I. “It will commit us to massive adaptation efforts so that for many, dislocation and migration becomes the only option.”

    Sea level rise is one of the most noticeable impacts of global warming, yet its effects are just starting to be seen, according to the article. The latest IPCC report calls for sea level rise of one meter by the year 2100. In the new study, however, the authors look at four different sea level-rise scenarios based on different rates of warming, from a low rate that could only be reached with massive efforts to eliminate fossil fuel use over the next few decades, to a higher rate based on the consumption of half the remaining fossil fuels over the next few centuries.

    With just two degrees (Celsius) warming in the low-end scenario, sea levels are predicted to eventually rise by about 25 meters. With seven degrees warming at the high-end scenario, the rise is estimated at 50 meters, although over a period of several centuries to millennia.

    “It takes sea level rise a very long time to react — on the order of centuries,” Clark said. “It’s like heating a pot of water on the stove; it doesn’t boil for quite a while after the heat is turned on — but then it will continue to boil as long as the heat persists. Once carbon is in the atmosphere, it will stay there for tens or hundreds of thousands of years, and the warming, as well as the higher seas, will remain.”

    For the low-end scenario, an estimated 122 countries have at least 10 percent of their population in areas that will be directly affected by rising sea levels, and some 1.3 billion people — or 20 percent of the global population — may be directly affected. The impacts become greater as the warming and sea level rise increases.

    The new paper makes the fundamental point that considering the long time scales of the carbon cycle and of climate change means that reducing emissions slightly or even significantly is not sufficient. “To spare future generations from the worst impacts of climate change, the target must be zero — or even negative carbon emissions — as soon as possible,” Clark said.

    The researchers’ work was supported by the U.S. National Science Foundation, the U.S. Department of Energy, the Natural Sciences and Engineering Research Council of Canada, the German Science Foundation and the Swiss National Science Foundation.

    See the full article here .

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    LLNL Campus

    Operated by Lawrence Livermore National Security, LLC, for the Department of Energy’s National Nuclear Security
    DOE Seal

  • richardmitnick 12:03 pm on February 8, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , DNA studies, Scientists Propose "Pumpjack" Mechanism for Splitting and Copying DNA   

    From BNL: “Scientists Propose “Pumpjack” Mechanism for Splitting and Copying DNA” 

    Brookhaven Lab

    High-resolution structural details of cells’ DNA-replicating proteins offer new insight into how these molecular machines function

    February 8, 2016
    Karen McNulty Walsh, (631) 344-8350
    Peter Genzer, (631) 344-3174

    BNL Mcm2-7 hexamer
    Two images showing the structure of the helicase protein complex from above. (a) A surface-rendered three-dimensional electron density map as obtained by cryo-EM. (b) A computer-generated “ribbon diagram” of the atomic model built based on the density map. The helicase has three major components: the Mcm2-7 hexamer ring in green, which encircles the DNA strand; the Cdc45 protein in magenta; and the GINS 4-protein complex in marine blue. Cdc45 and GINS recruit and tether other replisome components to the helicase, including the DNA polymerases that copy each strand of the DNA.

    New close-up images of the proteins that copy DNA inside the nucleus of a cell have led a team of scientists from the U.S. Department of Energy’s Brookhaven National Laboratory, Stony Brook University, Rockefeller University, and the University of Texas to propose a brand new mechanism for how this molecular machinery works. The scientists studied proteins from yeast cells, which share many features with the cells of complex organisms such as humans, and could offer new insight into ways that DNA replication can go awry.

    “DNA replication is a major source of errors that can lead to cancer,” explained Huilin Li, a biologist with a joint appointment at Brookhaven Lab and Stony Brook University and the lead author on a paper describing the new results in Nature Structural & Molecular Biology. “The entire genome—all 46 chromosomes—gets replicated every few hours in dividing human cells,” Li said, “so studying the details of how this process works may help us understand how errors occur.”

    The research builds on previous work by Li and others, including last year’s collaboration with the same team that produced the first-ever images of the complete DNA-copying protein complex, called the replisome.

    A representation of the structures of the replisome during DNA replication

    That study revealed a surprise about the location of the DNA-copying enzymes—DNA polymerases. This new study zooms in on the atomic-level details of the “helicase” portion of the protein complex—the part that encircles and splits the DNA double helix so the polymerases can synthesize two daughter strands by copying from the two separated parental strands of the “twisted ladder.”

    The scientists produced high-resolution images of the helicase using a technique known as cryo-electron microscopy (cryo-EM). One advantage of this method is that the proteins can be studied in solution, which is how they exist in the cells.

    “You don’t have to produce crystals that would lock the proteins in one position,” Li said. That’s important because the helicase is a molecular “machine” made of 11 connected proteins that must be flexible to work. “You have to be able to see how the molecule moves to understand its function,” Li said.

    download mp4 video here .

    download mp4 video here .

    The top movie shows the helicase protein complex from all angles, and reveals how its shape changes back and forth between two forms. The bottom movie shows how the rocking action of this conformational change might split the DNA double helix and move the helicase along one strand so it can be copied by DNA polymerase.

    Using computer software to sort out the images revealed that the helicase has two distinct conformations—one with components stacked in a compact way, and one where part of the structure is tilted relative to a more “fixed” base.

    The atomic-level view allowed the scientists to map out the locations of the individual amino acids that make up the helicase complex in each conformation. Then, combining those maps with existing biochemical knowledge, they came up with a mechanism for how the helicase works.

    “One part binds and releases energy from a molecule called ATP. It converts the chemical energy into a mechanical force that changes the shape of the helicase,” Li said. After kicking out the spent ATP, the helicase complex goes back to its original shape so a new ATP molecule can come in and start the process again.

    “It looks and operates similar to an old style pumpjack oil rig, with one part of the protein complex forming a stable platform, and another part rocking back and forth,” Li said. Each rocking motion could nudge the DNA strands apart and move the helicase along the double helix in a linear fashion, he suggested.

    This linear translocation mechanism appears to be quite different from the way helicases are thought to operate in more primitive organisms such as bacteria, where the entire complex is believed to rotate around the DNA, Li said. But there is some biochemical evidence to support the idea of linear motion, including the fact that the helicase can still function even when the ATP hydrolysis activity of some, but not all, of the components is knocked out by mutation.

    “We acknowledge that this proposal may be controversial and it is not really proven at this point, but the structure gives an indication of how this protein complex works and we are trying to make sense of it,” he said.

    The study was funded by the U.S. National Institutes of Health and the Howard Hughes Medical Institute (HHMI), with additional support from the Brookhaven Lab Biology Department. High-resolution cryo-EM data were collected at HHMI and the University of Texas Health Science Center.

    See the full article here .

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    BNL Campus

    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.

  • richardmitnick 9:30 am on February 8, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , Georgetown University   

    From Georgetown: “Gene family turns cancer cells into aggressive stem cells that keep growing” 

    Georgetown University bloc


    February 5, 2016
    Karen Teber

    An examination of 130 gene expression studies in 10 solid cancers has found that when any of four related genes is overexpressed, patients have much worse outcomes, including reduced survival.

    Researchers from Georgetown Lombardi Comprehensive Cancer Center say their study, published Feb. 5 in Oncotarget, shows that this Ly6 family of genes allows cancer cells to act like cancer stem cells — which keep dividing and growing without pause.

    Ly6 gene oncogene
    MedicalXpress from Oncotarget

    “These are remarkable findings. We believe this family of genes produces cancer that easily metastasizes, is drug resistant and very difficult to destroy,” says the study’s senior investigator, Geeta Upadhyay, PhD, research assistant professor of oncology at Georgetown Lombardi.

    Upadhyay and her collaborators are currently working on novel agents that can inhibit Ly6 gene expression.

    Upadhyay’s research was initially based on Sca1, a mouse gene investigators use to check for the presence of cancer stem cells in animals. In 2011, she found that Sca1 was more than just a biomarker — it played a key role in creating and maintaining the stem-like quality in cancer stem cells.

    She then looked to see if Sca1 works the same way in humans, and found a family of Ly6 genes that mapped to the same chromosomal location in humans where Sca1 resides in the mouse genome. The Ly6 family of genes was structurally similar to Sca1 as well.

    This study was designed to determine if any of the genes in the Ly6 family are important in human cancer.

    The researchers used 130 published, publicly available studies that included information on patients’ genes and their cancer outcomes. Some studies were from the Georgetown Database of Cancer; others were available at the National Institutes of Health.

    They discovered that four different members of the family — Ly6D, Ly6E, Ly6H, or Ly6K — are not active in normal tissue but are expressed in bladder, brain and central nervous system, colorectal, cervical, ovarian, lung, head and neck, pancreatic and prostate cancers. Investigators also found that high expression of these genes are linked to poor outcomes and reduced survival in ovarian, colorectal, gastric, lung, bladder and brain and central nervous system cancers.

    “Correlation between Ly6 gene expression and poor patient survival in multiple cancer types indicate that this family of genes will be important in clinical practice — not only as a marker of poor prognosis, but as targets for new drugs,” Upadhyay says.

    This study of big data supports the “cancer moonshot” proposal to speed up research announced by President Obama at this year’s State of the Union address, Upadhyay says. “The cancer field makes rapid progress when researchers share data and this study, which examines the work of scores of research teams, illustrates what can be done.”

    “We applied bioinformatic tools to explore the clinical significance of increased LY6 in survival outcome in multiple cancer types. Systems biology tools are critical for steering basic research to solve critical clinical challenges and identify novel signaling nodes such as this one,” says co-author Subha Madhavan, PhD, director of the Innovation Center for Biomedical Informatics at Georgetown.

    Other researchers participating in the study are Georgetown researchers Linlin Luo, Peter McGarvey PhD, and Yuriy Gusev, PhD, all from the Innovation Center for Biomedical Informatics, and Rakesh Kumar, PhD.

    This work was supported by a grant from the National Cancer Institute (1R21CA175862-01A1) and an American Cancer Society Institutional Research Grant.

    See the full article here .

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    Georgetown University campus

    Georgetown University is one of the world’s leading academic and research institutions, offering a unique educational experience that prepares the next generation of global citizens to lead and make a difference in the world. We are a vibrant community of exceptional students, faculty, alumni and professionals dedicated to real-world applications of our research, scholarship, faith and service.

    Established in 1789, Georgetown is the nation’s oldest Catholic and Jesuit university. Drawing upon the 450-year-old legacy of Jesuit education, we provide students with a world-class learning experience focused on educating the whole person through exposure to different faiths, cultures and beliefs. Students are challenged to engage in the world and become men and women in the service of others, especially the most vulnerable and disadvantaged members of the community.

    These values are at the core of Georgetown’s identity, binding members of the community across diverse backgrounds.

  • richardmitnick 1:07 am on February 8, 2016 Permalink | Reply
    Tags: Applied Research & Technology, Climate studies,   

    From Nature: “Job cuts in Australia target climate scientists” 

    Nature Mag

    05 February 2016
    Myles Gough

    National science agency announces strategic shift away from measuring and modelling climate change.

    Hundreds of climate researchers at Australia’s national science agency are set to lose their jobs after the organization announced that it would shift its strategy away from basic climate science.

    The Commonwealth Scientific and Industrial Research Organisation (CSIRO) employs thousands of scientists across Australia, and has been a leader in climate modelling and ocean observation in the Southern Hemisphere for decades.

    CSIRO bloc

    But in an e-mail sent to CSIRO staff members this week, chief executive Larry Marshall wrote that he expected the agency to shed up to 350 jobs over the next two years, of which the burden would fall on climate-science areas, including research divisions in the Oceans and Atmosphere and Land and Water units.

    Climate models and measurements had now proven the existence of global climate change, Marshall wrote, and the questions for the organization would now be: “What do we do about it” and “how can we find solutions for the climate we will be living with?” A spokesperson for CSIRO said that the cuts from climate-research units were a strategic decision.

    “The CSIRO is effectively saying ‘climate science is done and we’re moving on to adaptation and mitigation’,” says John Church, an expert in sea-level rise in the Ocean and Atmosphere unit who has spent 38 years with the organization. “My view is that there is inaccurate and misleading science in that statement — climate science is not done,” he says.

    Another senior scientist from the unit, who spoke to Nature on the condition of anonymity, says that 220 jobs will be cut from the two units; the 110 cuts from his unit will draw directly from the roughly 130 scientists (of the unit’s 421 staff) who work on climate science-related activities, he says. “More than 80% [of our climate scientists] will be cut. This is not about myself, it’s about my people and the capability we spent 40 years to build. It will be going overnight.”

    Disastrous move

    Other Australian researchers were quick to condemn the announcement. “This is a disastrous move that will decimate ocean and climate sciences in Australia,” Matthew England, co-director of the University of New South Wales’ Climate-Change Research Centre in Sydney, told the Australian Science Media Centre (SMC) in Adelaide.

    Penny Sackett, an astronomer at the Australian National University in Canberra, and a former chief scientist for the country, told the SMC that she was “stunned by reports that CSIRO management no longer thinks measuring and understanding climate change is important, innovative or impactful”.

    Andrew Holmes, president of the Australian Academy of Science in Canberra, said in a statement that the CSIRO job losses followed cuts of more than Aus$20 million (US$19 million) to climate and environmental science in the 2014–15 federal budget, and meant that there was “serious concern” about the country’s ability to conduct research in the area.

    “We call on the government to quickly make alternative arrangements to continue a comprehensive national program of climate research,” he said.

    Australia’s science and innovation minister, Christopher Pyne, did not respond to Nature’s requests for comment.

    The cuts come after a difficult time for CSIRO, which employs more than 5,000 people but dropped 1,300 jobs in the two years up to June 2015, largely because of a 2014 federal budget that cut CSIRO funding by 16%, or roughly Aus$115 million, over four years.

    Despite the most recent job losses, a CSIRO spokesperson said, “we expect that after two years, staff numbers will be at the same levels they are now, or higher.” But Sam Popovski, the secretary of the CSIRO Staff Association, says that there are doubts that, with flat federal funding for the next three years, CSIRO will be able to keep its staffing levels stable.

    Nature doi:10.1038/nature.2016.19313

    See the full article here .

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    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

  • richardmitnick 11:41 am on February 7, 2016 Permalink | Reply
    Tags: 5 Things Built at Cornell Tech This Year, Applied Research & Technology,   

    From Cornell: “5 Things Built at Cornell Tech This Year” 

    Cornell Bloc

    Cornell University

    January 11, 2016 [This just popped up in social media. Cornell is not very good at social media.]

    Cornell Tech students, postdocs and staff are constantly building and innovating whether it’s in the classroom, at work and even during summer break.

    Here are 5 things built at Cornell Tech and demonstrated during Open Studio, our end-of-semester celebration of student, faculty and staff projects:

    Cornell robot car
    1) RoboTC
    Developed by Wilson Pulling, MEng ‘16, RoboTC makes it easier for makers to build robots. Pulling compares the difficulty of building robots today to developing software years ago and wants to make building robots as easy as building an app. RoboTC is a chip which attaches to any robot and allows makers to download functionalities from an “algorithm store” instead of coding them from scratch.

    This enables easy implementation of otherwise difficult tasks such as path planning and object recognition, which Pulling hopes will drastically expand the scope of maker projects and help them to make the leap from robotics tinkerers to robotics entrepreneurs.

    Cornell Spider Eyes
    2) Spider Eyes
    Connective Media student Joanna Zhang ‘16 built an application called Spider Eyes over her summer break. The program crawls Wikipedia and visualizes all the connected Wikipedia articles and their relationship with the searched term. The size of each node on the web of related pages shows the importance of that page to the search.

    Cornell Facepage
    3) Facepage
    As part of her Connective Media specialization project, Zhang is building Facepage. The software generates a timeline of news for a searched term or topic. For example, a search of Barack Obama would return thousands of news articles. Facepage gathers the information, summarizes it and presents it to users in a easy-to-comprehend timeline.

    4) Slice
    Jai Chaudhary, developer in residence and MEng ‘15, has built a semantic search system currently being used by radiologists at Weill Cornell Medical College. It searches patient records with more precision than previous systems. What separates Slice from a normal keyword search is its ability to filter out terms in negative context. For example, if a radiologist searches for patients with cancer on other platforms, results for ‘no cancer’ would show up as well. Slice allows for positive searches, saving radiologists valuable time sorting through records.

    Slice is currently being used by about 36 radiologists at Weill and has helped them compile 5,000 reports in just 2 months. The long term vision for Slice is to further understand contextual meaning of terms and combine it with radiologist search intent.

    Cornell City Hive
    5) City Hive
    City Hive is a mobile first e-commerce platform developed by Runway Startup Postdoc Roi Kliper and his team. The platform allows for buy buttons and calls to action to be seamlessly integrated within the content being viewed on webpages, apps and other digital media. City Hive is currently being used by multiple customers and is shifting the power equilibrium of commerce online.

    See the full article here .

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    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

  • richardmitnick 3:23 pm on February 6, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , , , New Bedrest Adventure Adds Artificial Gravity   

    From ESA: New Bedrest Adventure Adds Artificial Gravity 

    ESA Space For Europe Banner
    European Space Agency

    2 February 2016
    No writer credit found

    The human body is made for living on Earth – take away the constant pull of gravity and muscles and bones begin to waste away. Living in space is hard on astronauts and ways must be found to keep them fit and safe.

    ESA and NASA are planning to confine human subjects to bed for 60 days in 2017 in Cologne, Germany to probe the effects of spaceflight, with periods in a centrifuge to test if artificial gravity can keep them healthy.

    Bedrest studies offer a way of testing measures to counter some of the negative aspects of living in space. Volunteers are kept in beds with the head end tilted 6° below the horizontal. For 60 days one of the subject’s shoulders must be touching the bed at all times.

    As blood flows to the head and muscle is lost from underuse, researchers can investigate changes and test techniques from diet to physical exercise.

    Human centrifuge for artificial gravity

    The study will be conducted at the DLR German Aerospace Center’s :envihab flagship site in Cologne. Built from the ground up to research the human body under spaceflight conditions, it allows researchers to change almost every aspect of the environment, including humidity, daylight and temperature.

    ESA and DLR have already run their first study – spare a thought for the 12 brave volunteers who finished 60 days in bed last November – but this one will be the first to use the facility’s centrifuge. By spinning the subjects, the blood is encouraged to flow back towards the feet.

    The advantage of artificial gravity is that it has the potential of reducing most of the negative effects of weightlessness on the human body in one go.

    :envihab’s centrifuge can adjust the centre of spin so that subjects can be spun around their heads or chests. Changing the position could have far-reaching consequences for rehabilitation but, as this is a new domain, nobody knows yet.

    Jennifer Ngo-Anh, leading ESA’s human research, says, “I am happy to start this new bedrest study with our friends and colleagues from NASA, our first in 10 years. This study begins a series of bedrest studies focusing on artificial gravity, making use of the ESA-built centrifuges in Cologne and at MEDES in Toulouse, France.

    “This exciting research platform offers scientists around the world a way to collect results and contribute to long-duration missions to the Moon, Mars and even beyond.”

    The results are helping astronaut physicians to design better ways for astronauts to keep fit, but the knowledge is also directly applicable to bedridden people on Earth.

    Scientists are invited to submit research proposals via this link. The letter of intent is due by 15 February, with a workshop at ESA’s technical heart, ESTEC, on 22 February.

    DLR Bloc

    NASA image

    See the full article here .

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    The European Space Agency (ESA), established in 1975, is an intergovernmental organization dedicated to the exploration of space, currently with 19 member states. Headquartered in Paris, ESA has a staff of more than 2,000. ESA’s space flight program includes human spaceflight, mainly through the participation in the International Space Station program, the launch and operations of unmanned exploration missions to other planets and the Moon, Earth observation, science, telecommunication as well as maintaining a major spaceport, the Guiana Space Centre at Kourou, French Guiana, and designing launch vehicles. ESA science missions are based at ESTEC in Noordwijk, Netherlands, Earth Observation missions at ESRIN in Frascati, Italy, ESA Mission Control (ESOC) is in Darmstadt, Germany, the European Astronaut Centre (EAC) that trains astronauts for future missions is situated in Cologne, Germany, and the European Space Astronomy Centre is located in Villanueva de la Cañada, Spain.

    ESA50 Logo large

  • richardmitnick 12:46 pm on February 6, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , Pangaea,   

    From livescience: “What If the Supercontinent Pangaea Had Never Broken Up?” 


    Brought forward 2.6.16
    Original date May 13, 2011

    Adam Hadhazy

    Things would be a little different.

    Pangaea and its breakup

    From about 300 million to 200 million years ago, all seven modern continents were mashed together as one landmass, dubbed Pangaea . The continents have since “drifted” apart because of the movements of the Earth’s crust, known as plate tectonics. Some continents have maintained their puzzle piece-like shapes: Look at how eastern South America tucks into western Africa.

    Techtonic plates
    The tectonic plates of the world were mapped in the second half of the 20th century.

    Life would be: Far less diverse. A prime driver of speciation the development of new species from existing ones is geographical isolation, which leads to the evolution of new traits by subjecting creatures to different selective pressures. Consider, for example, the large island of Madagascar, which broke off from Gondwana, Pangaea’s southern half, 160 million years ago. About nine out of 10 of the plant and mammal species that have evolved on the island are not found anywhere else on the planet, according to Conservation International.

    A locked-in Pangaea further constrains life’s possibilities because much of its interior would be arid and hot, said Damian Nance, a professor of geosciences at Ohio University. “Because of Pangaea’s size, moisture-bearing clouds would lose most of their moisture before getting very far inland,” Nance told Life’s Little Mysteries.

    Excess mass on a spinning globe shifts away from the poles, so the supercontinent would also become centered on the equator, the warmest part of the planet. Reptiles could deal with such a climate better than most, which is partly why dinosaurs, which emerged during the time the planet’s surface was one giant chunk, thrived before mammals.

    See the full article here .

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  • richardmitnick 12:29 pm on February 6, 2016 Permalink | Reply
    Tags: Applied Research & Technology, , Nature Genetics   

    From Nature: “The many ways MYB drives cancer” 

    Nature Mag

    free association
    free association from Nature Genetics

    Nature Genetics | Free Association

    05 Feb 2016
    Posted by Brooke LaFlamm

    Two papers published online this week in Nature Genetics demonstrate that MYB, long known as a cancer gene, has many different strategies for driving tumorigenesis.

    Fruitfly eye signals about cancer
    Fruitfly eye, evidence of cancer

    Bradley Bernstein, Birgit Knoechel and colleagues studied the role of MYB translocations in adenoid cystic carcinoma (ACC) and found that MYB translocations can reposition the gene to be driven by super-enhancers—which themselves are bound by MYB to drive its own expression even higher. In an interesting twist, they also found that MYB drives different regulatory programs in different ACC cell lineages: MYB’s oncogenic function is mediated by TP63 in myoepithelial cells, while in luminal epithelial cells, MYB appears to act through the Notch signaling pathway.

    In an independent study focused on pediatric angiocentric gliomas, Keith Ligon, Rameen Beroukhim, Adam Resnick and colleagues found that MYB translocations resulting in MYB-QKI fusion genes are the most common MYB alteration in this cancer type. The fusion results in higher expression of MYB and loss of QKI expression, both of which contribute to the development of these gliomas. As in the ACC study, this translocation resulted in repositioning of MYB near enhancers that help drive its expression up. At the same time, the translocation caused loss of some regulatory elements, also leading to aberrant expression of MYB, and loss of function of QKI, a tumor suppressor. Thus, MYB-QKI uses three different mechanisms to drive gliomagenesis.

    Both cancer types are relatively rare but aggressive, and new treatment options are sorely needed. Adenoid cystic carcinoma (ACC) occurs in secretory glands, mainly the salivary glands in the head and neck, and can spread to the nerves as well as metastasizing to distant sites, such as the lungs. The tumors are often resistant to therapy and can recur many years after the primary tumor has been removed surgically. Angiocentric gliomas are very rare brain tumors that generally affect children and young adults. Very little is known about the genetic changes that occur in this tumor type and, prior to this study, there were no known recurrent driver mutations, which are often good candidates for new targeted drug therapies. “The discovery of a recurrent rearrangement in angiocentric glioma provides a clinically relevant diagnostic marker, and insights into the biology that drives these tumors,” said Pratiti Bandopadhayay, one of the lead authors of the study.

    We asked some of the authors from both studies to tell us a little more about the work and why it is important. Yotam Drier and Birgit Knoechel talked to us about the study in ACC. Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain talked to us about the study in angiocentric gliomas.

    How do your findings clarify earlier results showing a role for MYB in ACC? Do you think these findings are relevant for other cancer types?

    Yotam Drier and Birgit Knoechel (Broad Institute):

    Our work identified a unifying mechanism for MYB over-expression in ACC. Persson et al. suggested in 2009 that MYB over-expression occurs where the MYB 3′ untranslated region (UTR) is lost. However, in most cases of ACC the MYB 3′ UTR remains intact, and we now describe that in all cases of detected MYB rearrangements in this cancer–independent of whether the 3′ UTR is retained or lost–MYB is being driven by hijacking MYB bound super-enhancers, thus creating a positive feedback loop. This is complementary to the previous model, and we believe that in those cases where the MYB 3′ UTR is lost, both mechanisms would contribute to increased MYB expression.

    We believe that similar rearrangements involving enhancer translocations may contribute to MYB overexpression in other cancer types. For example, our colleagues at Dana Farber simultaneously report a similar mechanism of MYB activation in angiocentric gliomas.

    How do the mechanisms described in your paper compare to what is described in the related paper by Drier et al.?

    Pratiti Bandopadhayay, Lori Ramkissoon and Guillaume Bergthold (Dana-Farber Cancer Institute) and Payal Jain (Children’s Hospital of Philadelphia):

    We were excited to learn about the findings from the Bernstein group as their findings compliment ours, in a completely different tumor type. We found that angiocentric gliomas harbor rearrangements involving the MYB and QKI genes, while Dr. Bernstein’s team focused on adenoid cystic carcinomas, which frequently have similar MYB rearrangements. Both papers show that MYB rearrangements result in aberrant activation of the MYB promoter to drive expression of the oncogenic fusion proteins, and that these fusion proteins then participate in auto-regulatory feedback loops to drive their own expression.

    From your perspective, what was the most unexpected finding in this study?

    Yotam Drier and Birgit Knoechel:

    We were surprised by our finding that MYB orchestrates 2 opposing epigenetic states—a TP63-dependent program in myoepithelial cells and a NOTCH-dependent program in luminal cells. Thus, overexpression of a single transcription factor can drive distinct epigenetic states that depend on the cellular context in which the overexpression occurs.

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    The unexpected result of our study that we find very exciting is that this one single driver rearrangement contributes to tumor growth through multiple mechanisms. MYB-QKI rearrangements simultaneously drive expression of a fusion protein that causes cells to grow faster and form tumors, it changes the regulatory landscape of the gene to promote expression of this protein and it simultaneously disrupts a tumor suppressor gene (QKI) that in turn also makes the cells divide faster. We feel that this finding is likely relevant to a number of other pediatric and adult cancers.

    How does the fusion with QKI impact the function of the translocated MYB and do you think it is necessary for its role in driving gliomagenesis?

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    The rearrangement with QKI results in displacement of regulatory elements on QKI towards MYB and these elements help drive expression of MYB-QKI. In addition, it disrupts the function of QKI itself, which is a tumor suppressor gene. We feel that the association with QKI is important in angiocentric glioma since the rearrangement between MYB and QKI occurred with such high frequency in our study.

    What are the additional steps needed before your findings can be implemented in the clinic?

    Yotam Drier and Birgit Knoechel:

    Interestingly, while BET inhibition can slow tumor growth in low grade ACCs, high grade ACCs often show genetic activation of NOTCH and are thus amenable to treatment with gamma secretase inhibitors or other NOTCH targeting therapies. It will be important to evaluate whether combining BET inhibition with NOTCH inhibition may show additional effects over BET inhibition alone. It is conceivable that by adding the NOTCH inhibitor one might preferentially target the luminal epithelial cells which are characterized by a NOTCH driven regulatory program. This will need to be tested further in preclinical models. Moreover, the fact that grade 3 tumors failed to respond to BET inhibition requires further preclinical analyses. Identifying mechanisms of BET inhibitor failure which are just entering clinical trials will be of utmost importance in order to predict which patients may benefit from these.

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    We are excited that our results provide us with novel possibilities to treat angiocentric gliomas. As MYB is a transcription factor the likelihood of targeting it or the MYB-QKI fusion is challenging; however we identified several downstream targets that represent potential therapeutic strategies. In addition, the finding of altered regulatory elements represents another exciting therapeutic strategy. Our findings directly impact clinical care for children with angiocentric glioma through development of two diagnostic tests that will be used to support the diagnosis of angiocentric glioma. We also feel our findings are likely relevant to other pediatric and adult cancers that are driven by driver rearrangements.

    Finally we would like to highlight that multiple institutions and funding sources helped facilitate this study. We would also like to acknowledge the families whose children have been afflicted with Pediatric Low-Grade Glioma.

    See the full article here .

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    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

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