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  • richardmitnick 7:45 am on October 7, 2014 Permalink | Reply
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    From SLAC: “Study Reveals ‘Bellhops’ in Cell Walls Can Double as Hormones” 


    SLAC Lab

    October 6, 2014

    Discovery at SLAC’s Synchrotron Could Lead to New Drug Designs, Treatments

    Researchers have discovered that some common messenger molecules in human cells double as hormones when bound to a protein that interacts with DNA. The finding could bring to light a class of previously unknown hormones and lead to new ways to target diseases – including cancers and a host of hormone-related disorders.

    image
    In this rendering, the structure of the nuclear receptor transcription factor Steroidogenic Factor-1 (SF-1, shown in gray) is bound by the signaling phospholipid referred to as “PIP3″ (blue and red). (Raymond Blind/UCSF)

    Published in the Oct. 6 edition of Proceedings of the National Academy of Sciences, these results were made possible, in part, by X-ray experiments at the Department of Energy’s SLAC National Accelerator Laboratory.

    “This finding is comparable in its importance to the discovery of how the estrogen hormone triggers activity in human cells, which was key in the development of anti-breast cancer drugs and other hormone treatments,” Robert Fletterick, professor of biochemistry and biophysics at University of California, San Francisco, and one of the principal investigators in the study, said.

    Resolving a Cellular Mystery

    Researchers focused on messengers called signaling phospholipids that act like bellhops in cell walls, escorting proteins to compartments within a cell and activating their functions. The results could explain why these messengers had been observed linked to proteins in the nucleus of cells; their purpose there had been a mystery.

    pj
    Renderings of a signaling phospholipid, PIP3, which was studied while bound to a nuclear receptor, SF-1. The phospholipid was found to behave as a hormone. (Raymond Blind/UCSF)

    X-ray crystallography at SLAC’s Stanford Synchrotron Radiation Lightsource, a DOE Office of Science User Facility, provided the first detailed look at how this messenger acts as a hormone in binding to a specialized hormone-sensing protein called a nuclear receptor.

    SLAC SSRL
    SLAC SSRL

    These receptors are known to interact with DNA in the cell’s nucleus and directly regulate gene expression – a critical mechanism for carrying out the cell’s functions. The experiment focused on a well-studied receptor called SF-1 because its mutations are believed to be associated with infertility and other reproductive disorders, and diseases including colon and pancreatic cancers.

    In analyzing X-ray data measured at SSRL, researchers observed how the phospholipids act like hormones when docked into the SF-1 receptors. Hormones are key links in the communications chain between different types of cells and organs that turn on specific genes in cells and activate a broad range of responses.

    “The greatest impact of this work might be to prompt scientists to take a new view of phospholipids and what they do in the cell,” said Holly A. Ingraham, a UCSF professor who participated in the study.

    “The idea that a component of a cell membrane such as a phospholipid could work as a hormone, triggering gene expression, is quite novel,” she said. “People have not really known what their role is in the nucleus. Now we can say for the first time we know why they are there: Some of them might be acting like hormones.”

    New Details in Bound Biomolecule

    Ray Blind, a UCSF postdoctoral researcher who led the study, devoted years of effort to finding a way to prepare crystallized samples of two types of phospholipids that were separately bound to the SF-1 receptor. High-quality crystals were needed to capture high-resolution X-ray data of their contents and determine the structure of the biomolecular complexes.

    Debanu Das, a staff scientist at SSRL’s Structural Determination Core of the Joint Center for Structural Genomics, oversaw the experiments at SSRL. Based on highly automated X-ray data collection and analysis of about 250 crystal samples, scientists were able to fully map the 3-D atomic-scale structure of the biomolecules, revealing never-before-seen details.

    Well-known hormones like estrogen and testosterone bind to and activate receptors by changing their shape. The study found that the phospholipids bind with the receptor protein in a more complex way than classic hormones do, which potentially enables the phospholipids to manipulate the shape of receptors in more profound ways.

    The researchers said they hope to design synthetic molecules that can target the disease-associated structures in the receptor protein.

    The Joint Center for Structural Genomics is a research consortium that includes SLAC’s SSRL; The Scripps Research Institute; the Genomics Institute of the Novartis Research Foundation; the University of California, San Diego; and the Sanford-Burnham Medical Research Institute. The joint center is supported by the National Institute of General Medical Sciences’ Protein Structure Initiative (PSI) and the National Institutes of Health. The research was also supported by the PSI-Biology Partnership for Stem Cell Biology. Support for the SSRL Structural Molecular Biology Program, whose X-ray facilities enabled the structural work, is provided by the DOE Office of Biological and Environmental Research and by the National Institute of General Medical Sciences.

    See the full article, with video, here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 3:46 pm on September 23, 2014 Permalink | Reply
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    From SLAC: “Research Pinpoints Role of ‘Helper’ Atoms in Oxygen Release” 


    SLAC Lab

    September 22, 2014

    System Studied at SLAC’s Synchrotron Mimics Steps in Photosynthesis

    Experiments at the Department of Energy’s SLAC National Accelerator Laboratory solve a long-standing mystery in the role calcium atoms serve in a chemical reaction that releases oxygen into the air we breathe. The results offer new clues about atomic-scale processes that drive the life-sustaining cycle of photosynthesis and could help forge a foundation for producing cleaner energy sources by synthesizing nature’s handiwork.

    The research is detailed in a paper published Sept. 14 in Nature Chemistry. X-ray experiments at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility, played a key role in the study, led by Wonwoo Nam at Ewha Womans University in Korea in a joint collaboration with Riti Sarangi, an SSRL staff scientist.

    SLAC SSRL
    SLAC SSRL

    “For the first time, we show how calcium can actually tune this oxygen-releasing reaction in subtle but precise ways,” said Sarangi, who carried out the X-ray work and supporting computer simulations and calculations. “The study helps us resolve the question, ‘Why does nature choose calcium?'”

    Photosynthesis is one of many important biological processes that rely on proteins with metal-containing centers, such as iron or manganese. The chemistry carried out in such centers is integral to their function. Scientists have known that the presence of calcium is necessary for the oxygen-releasing stages of photosynthesis, but they didn’t know how or why.

    The SSRL experiment used a technique known as X-ray absorption spectroscopy to explore the chemical and structural details of sample systems that mimic of the oxygen-releasing steps in photosynthesis. The basic oxygen-releasing system contained calcium and was centered around an iron atom.

    Researchers found that charged atoms, or ions, of calcium and another element, strontium, bind to the oxygen atoms in a way that precisely tunes the chemical reaction at the iron center. This, in turn, facilitates the bond formation between two oxygen atoms. The study also revealed that calcium and strontium do not obstruct the release of these bound oxygen atoms into the air as an oxygen molecule — the final step in this reaction.

    “We saw that unless you use calcium or strontium, this sample system will not release oxygen,” Sarangi said. “Calcium and strontium bind at just the right strength to facilitate the oxygen release. Anything that binds too strongly would impede that step.”

    While the sample system studied is not biological, the chemistry at work is considered a very good analogue for the oxygen-releasing steps carried out in photosynthesis, she said, and could assist in constructing artificial systems that replicate these steps. The next step will be to study more complex samples that perform more closely to the actual chemistry in photosynthesis.

    Other participants in this research were from Osaka University in Japan and the Japan Science Technology Agency. The research was supported by the National Research Foundation of Korea and the Ministry of Education, Culture, Sports, Science and Technology in Japan. SSRL’s Structural Molecular Biology program is supported by the National Institutes of Health and the Office of Biological and Environmental Research of the U.S. Department of Energy.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 5:33 am on August 16, 2014 Permalink | Reply
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    From Brookhaven Lab: “Harnessing the Power of Bacteria’s Sophisticated Immune System” 

    Brookhaven Lab

    August 15, 2014
    Karen McNulty Walsh, (631) 344-8350 or Peter Genzer, (631) 344-3174

    Researchers Now Better Understand How Bacteria Can So Quickly Protect Itself From Harm, Could Help Unlock Clues About Antibiotic Resistance

    Bacteria’s ability to destroy viruses has long puzzled scientists, but researchers at the Johns Hopkins Bloomberg School of Public Health say they now have a clear picture of the bacterial immune system and say its unique shape is likely why bacteria can so quickly recognize and destroy their assailants.

    The researchers drew what they say is the first-ever picture of the molecular machinery, known as Cascade, which stands guard inside bacterial cells. To their surprise, they found it contains a two-strand, unencumbered structure that resembles a ladder, freeing it to do its work faster than a standard double-helix would allow.

    The findings, published online Aug. 14 in the journal Science, may also provide clues about the spread of antibiotic resistance, which occurs when bacteria adapt to the point where antibiotics no longer work in people who need them to treat infections, since similar processes are in play. The World Health Organization (WHO) considers antibiotic resistance a major threat to public health around the world.

    “If you understand what something looks like, you can figure out what it does,” says study leader Scott Bailey, PhD, an associate professor in the Bloomberg School’s Department of Biochemistry and Molecular Biology. “And here we found a structure that nobody’s ever seen before, a structure that could explain why Cascade is so good at what it does.”

    For their study, Bailey and his colleagues used something called X-ray crystallography to draw the picture of Cascade, a key component of bacteria’s sophisticated immune system known as CRISPR, an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. Cascade uses the information housed in sequences of RNA as shorthand to identify foreign invaders and kill them.

    crispr
    Diagram of the possible mechanism for CRISPR

    Much of the human immune system is well understood, but until recently scientists didn’t realize the level of complexity associated with the immune system of single-cell life forms, including bacteria. Scientists first identified CRISPR several years ago when trying to understand why bacterial cultures used to make yogurt succumbed to viral infections. Researchers subsequently discovered they could harness the CRISPR bacterial immune system to edit DNA and repair damaged genes. One group, for example, was able to remove viral DNA from human cells infected with HIV.

    Bailey’s work is focused on how Cascade is able to help bacteria fight off viruses called bacteriophages. The Cascade system uses short strands of bacterial RNA to scan the bacteriophage DNA to see if it is foreign or self. If foreign, the cell launches an attack that chews up the invading bacteriophage.

    bac
    The structure of a typical myovirus bacteriophage

    To “see” how this happens, Bailey and his team converted Cascade into a crystalized form. Technicians at the National Synchrotron Light Source at Brookhaven National Laboratory in Upton, New York, and the Stanford Synchrotron Radiation Lightsource then trained high-powered X-rays on the crystals. The X-rays provided computational data to the Bloomberg School scientists allowing them to draw Cascade, an 11-protein machine that only operates if each part is in perfect working order.

    Brookhaven NSLS
    Brookhaven NSLS

    SLAC SSRL
    SLAC SSRL

    What they saw was unexpected. Instead of the RNA and DNA wrapping around each other to form what is known as a double-helix structure, in Cascade the DNA and RNA are more like parallel lines, forming something of a ladder. Bailey says that if RNA had to wrap itself around DNA to recognize an invader – and then unwrap itself to look at the next strand – the process would take too much time to ward off infection. With a ladder structure, RNA can quickly scan DNA.

    ah
    Annie Heroux at NSLS

    In the new study, Bailey says his team determined that the RNA scans the DNA in a manner similar to how humans scan text for a key word. They break long stretches of characters into smaller bite-sized segments, much like words themselves, so they can be spotted more easily.

    Since the CRISPR-Cas system naturally acts as a barrier to the exchange of genetic information between bacteria and bacteriophages, its function can offer clues to how antibiotic resistance develops and ideas for how to keep it from happening.

    “We’re finding more pieces to the puzzle,” Bailey says. “This gives us a better understanding of how these machines find their targets, which may help us harness the CRISPR system as a tool for therapy or manipulation of DNA in a lab setting. And it all started when someone wanted to make yogurt more cheaply.”

    “Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target” was written by Sabin Mulepati, Annie Heroux and Scott Bailey.

    This work was funded by a grant from the National Institute of Health’s National Institute of General Medical Sciences (GM097330).

    See the full article here.

    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 2:51 pm on August 14, 2014 Permalink | Reply
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    From SLAC Lab: “SLAC Secures Role in Energy Frontier Research Center Focused on Next-generation Materials” 


    SLAC Lab

    August 14, 2014

    X-ray Studies will Explore Hybrid Materials for Solar Energy, Efficient Lighting and Other Uses

    he Department of Energy’s SLAC National Accelerator Laboratory will play a key role in a research consortium that seeks out new materials for next-generation solar panels, low-energy lighting and other uses.

    Collaborators in this effort will use SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility, to characterize these new materials as they are being discovered.

    tunnel
    SLAC SSRL Accelerator Tunnel

    strip
    A researcher at SLAC’s Stanford Synchrotron Radiation Lightsource holds up a thin strip of material printed with an ink (magenta) relevant to solar-energy conversion. SSRL will play a role in a new center, led by the National Renewable Energy Laboratory in Colorado, that will explore new materials for solar panels, energy-efficient lighting and other uses. (SLAC National Accelerator Laboratory)

    The collaboration will also aid in understanding their structure and performance as they operate. The work is made possible by a four-year, $14 million DOE award for an Energy Frontier Research Center (EFRC) distributed among several national labs and universities.

    “We are pushing the idea of ‘materials by design’ to the next step,” said Mike Toney, an SSRL senior staff scientist and head of the SSRL Materials Science Division. Toney will oversee SLAC’s contributions to this Center for Next Generation of Materials by Design: Incorporating Metastability, which is led by the National Renewable Energy Laboratory (NREL) in Colorado.

    “It’s a theory-centric center that aims to tell you what materials to make and how to make them,” Toney added. SLAC’s role will be purely experimental: investigating the novel materials with a slew of X-ray techniques. Watching materials as they’re being made and while they’re operating are already SSRL specialties, Toney said.

    “SLAC is a key partner on our EFRC team, bringing unique characterization tools to probe and understand new materials, including the processes that control their formation,” Bill Tumas, EFRC director and associate lab director for materials and chemistry at NREL, said.

    The center is one of 32 EFRCs approved by the DOE in June, which follow an initial batch of DOE research centers approved five years ago. According to Toney, SLAC played an important role in one of the earlier centers, the Center for Inverse Design, which was also led by NREL and laid the groundwork for the new round of research.

    In materials science it’s common to work from known materials and modify them to achieve desired properties. The Center for Inverse Design sought to flip this approach on its head by using theory integrated with experiment to discover new materials with desired properties.

    The new center stretches this idea to a realm where the sought-after material properties are complex and theory and computation are not fully developed. It will initially focus on creating new semiconductor materials that can be incorporated into solar energy conversion systems and solid-state lighting technologies that use less power than standard light bulbs.

    It also aims to tackle “multiple-property design” – tailoring materials with several enhanced properties. And it will explore lesser-understood “metastable” materials, which can have desirable traits but are not in their most stable state – they can fall back to a lower, more stable energy level when disturbed, for example.

    “These centers are bringing together different groups of people who normally would not converse,” Toney said, which makes for lively discussions and innovative approaches to scientific challenges.

    Other participants in the new research center, which starts up this summer, are from Oregon State University, Colorado School of Mines, the Massachusetts Institute of Technology, Lawrence Berkeley National Laboratory and Harvard University.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 2:15 pm on July 29, 2014 Permalink | Reply
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    From SLAC: “New Platinum Alloy Shows Promise as Fuel Cell Catalyst” 


    SLAC Lab

    July 21, 2014

    Highly Efficient Nanoparticles Could Bring Down the Cost of Fuel Cells

    Fuel cells are a promising, non-polluting way to power cars, but their platinum catalysts are so expensive that there’s no way current technology could be economically scaled up for widespread use. Now scientists at the Department of Energy’s SLAC National Accelerator Laboratory and the Technical University of Denmark have developed an alternative that would use just one-fifth as much of the pricey metal.

    The new catalyst is a mixture of platinum and a second, cheaper element, yttrium, formed into nanoparticles whose size can be precisely controlled. Electron microscopy and X-ray studies show that yttrium atoms leach out of the surface of these particles, leaving a thin, dense, sturdy crust of platinum atoms to enthusiastically promote a key reaction in the fuel cell that converts oxygen molecules into water.

    The results were published July 13 in Nature Chemistry.

    “We now have proof of principle that these nanoparticles work the way we had predicted,” said report co-author Daniel Friebel, an associate staff scientist at SUNCAT Center for Interface Science and Catalysis, which is jointly run by SLAC and Stanford University. “The next step is to find a more efficient way to make these nanoparticles so they can be mass-produced.”

    Wanted: Cheaper Fuel Cells

    car
    Scientists at SLAC National Accelerator Laboratory and Technical University of Denmark have developed a new fuel cell catalyst that uses much less pricey platinum and is five times more active than platinum alone. If developed commercially, the new catalyst could bring down the cost of fuel cells for vehicles. (iStockphoto.com/gchutka)

    All but a handful of today’s electric vehicles run on batteries, which are heavy and can only store so much energy; that’s why electric cars have a limited range. Fuel cells are an attractive alternative because they’re small and light and could run on a tank full of hydrogen replenished at a fueling station. In addition, the car’s exhaust would contain nothing but pure water.

    But the catalyst that breaks down oxygen molecules in a fuel cell requires five to 10 times more platinum than the catalytic converter that scrubs pollutants from conventional engine exhaust. With the price of platinum nearly $1,500 an ounce, running the world’s automotive fleet on fuel cells would be prohibitively expensive.

    “The number one goal is to minimize how much platinum you use, and you can only realize that goal with nanoparticles,” Friebel said. “That’s because the catalytic reaction happens only at the surface of the material; and the smaller the particle, the larger the surface area it has with respect to its interior volume.”

    But the smaller the particles, he said, the more unstable they become. Scientists have combined platinum with other elements, such as nickel, to make catalysts that initially outperformed pure platinum, but later fell behind as the non-platinum part of the alloy corroded away.

    About five years ago, SUNCAT Director Jens Nørskov, a theorist who was then at Technical University of Denmark (DTU), and his coworkers suggested that a mixture of platinum and yttrium might do the trick. This seemed like an odd choice; yttrium likes to react with oxygen, which does not bode well for its stability, and the alloy would prove difficult to synthesize. But initial samples made by a company in Germany turned out to be both stable and a decent catalyst.

    Testing an Unlikely Combo

    To turn the samples into nanoparticles, researchers at DTU bombarded the alloy with argon ions in a vacuum chamber. This knocked out atoms of platinum and yttrium, which cooled and stuck together to form nanoparticles. The scientists sorted the particles by size and discovered that some of the larger ones – about 9 nanometers in diameter – had the best catalytic activity, five times better than today’s pure platinum catalysts.

    Then the scientists examined the nanoparticles with X-ray beams at SLAC’s Stanford Synchrotron Radiation Lightsource, a DOE Office of Science user facility, to find out what made them so active. They found that the larger yttrium atoms had escaped from the surfaces of the particles, leaving a surface crust in which the smaller platinum atoms packed together more tightly than usual in a very stable configuration.

    For a commercial catalyst, Friebel said, the team will need to find a more efficient way to make the nanoparticles. They’ll also see if they can tune the density of the platinum crust so it will perform its tasks of bond-breaking and bond-making to convert oxygen into water even faster.

    The 15-member research team included Patricia Hernandez-Fernandez, Ifan E.L Stephens and Ib Chorkendorff at DTU and Anders Nilsson of SUNCAT. Support for this research came from the Danish Ministry of Science, the Danish National Research Foundation, the A.P. Møller and Chastine Mc-Kinney Møller Foundation, the Interdisciplinary Center for Electron Microscopy at EPFL and the DOE Office of Science.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 7:36 pm on July 22, 2014 Permalink | Reply
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    From SLAC: “Bringing High-energy X-rays into Better Focus” 


    SLAC Lab

    July 22, 2014
    SLAC-invented Etching Process Builds Custom Nanostructures for X-ray Optics

    Scientists at the Department of Energy’s SLAC National Accelerator Laboratory have invented a customizable chemical etching process that can be used to manufacture high-performance focusing devices for the brightest X-ray sources on the planet, as well as to make other nanoscale structures such as biosensors and battery electrodes.

    “The tools researchers use to manipulate X-rays today are very limited,” said Anne Sakdinawat, an associate staff scientist at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) who developed the new “V-MACE” process with Chieh Chang, an SSRL research associate.

    scan
    Scanning electron microscope image of a cleaved spiral zone plate, a type of X-ray optic, created using a chemical etching technique that was developed at SLAC. (Chieh Chang, Anne Sakdinawat)

    “Our new technique for fabricating high performance X-ray optics involves just a few chemicals in a simple, easy-to-implement, one-step technology,” Sakdinawat said. “It offers significant advantages in many far-ranging applications.” The patent-pending technique is detailed in the June 27 edition of Nature Communications.

    Focusing X-rays, particularly higher-energy or “hard” X-rays, is particularly challenging at the nanoscale, though it is key to the success of many scientific studies at two of SLAC’s DOE Office of Science user facilities, SSRL and the Linac Coherent Light Source (LCLS) X-ray laser.

    It is also of great interest for commercial applications such as X-ray microscopy, complex electronics, and biomedical devices and imaging tools.

    Existing tools for focusing hard X-rays, such as specialized mirrors and sequences of concave metal structures that form lenses, are generally limited in how they can shape the X-ray light. Focusing the highest-energy X-rays to produce crisp images remains a challenge, as the focusing tools themselves generally lack nanoscale precision and sap away much of the X-ray energy.

    “It’s been technologically very difficult to fabricate structures that offer both high resolution and high efficiency,” Sakdinawat said, and the effectiveness of the structures, which are examples of X-ray “diffractive optics,” is typically based on the height and precision of their features.

    The new fabrication technique is adapted from a process used to create hairlike silicon wires for research on advanced batteries and electronics. It can fabricate structures up to 100 times as tall as they are wide, with dimensions accurate to billionths of a meter. The technique reduces the need to stack multiple layers to create tall structures.

    The researchers used the etching technique to build tall, precise X-ray diffractive optics, called zone plates, whose thinly spaced lines, symmetric rings or spiral patterns alternately obstruct or phase-shift X-rays and allow them to pass through in a way that separates and refocuses them. This improves the focus and produces higher-quality images.

    zone
    Scanning electron microscope (SEM) image of a zone plate pattern produced using a chemical etching technique invented at SLAC. (Chieh Chang, Anne Sakdinawat)

    zone2
    This scanning electron microscope image shows a cross-sectional view of a zone plate produced using a patent-pending chemical etching technique called “V-MACE” developed at SLAC. (Chieh Chang, Anne Sakdinawat)

    “Basically, this is like an artificial crystal,” Sakdinawat said, diffracting the X-ray light in a predictable pattern, as a crystal would. “You can basically manipulate the light in whatever fashion you want – you can shape the light in different ways,” she said, based on the design of the optics and the needs of the experiment.

    Sakdinawat and Chang tested and imaged a sample zone plate at SSRL, and they hope to construct similar plates for use in experiments at SSRL and LCLS.

    The same technique can be used to build other types of precise silicon and metal-coated nanostructures, such as filtration devices, thermoelectric devices that can create electricity from heat and components for tiny bio-sensors that can be embedded in the body, and researchers are working to tailor the process to suit the needs of government agencies and corporate partners.

    “We’re trying to expand into other fields,” Sakdinawat said. “There are many different applications for this.”

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 4:50 pm on May 22, 2014 Permalink | Reply
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    From SLAC Lab: “Stanford Researchers Discover Immune System’s Rules of Engagement” 


    SLAC Lab

    May 22, 2014
    Media Contacts:
    K. Chris Garcia, Department of Molecular & Cellular Physiology, Stanford School of Medicine: (650) 498-7111, kcgarcia@stanford.edu
    Dan Stober, Stanford News Service: (650) 721-6965, dstober@stanford.edu
    Andy Freeberg, SLAC National Accelerator Laboratory: (650) 926-4359, afreeberg@slac.stanford.edu

    Study finds surprising similarities in the way immune system defenders bind to disease-causing invaders.

    A study led by researchers at Stanford’s School of Medicine reveals how T cells, the immune system’s foot soldiers, respond to an enormous number of potential health threats.

    t
    Stanford School of Medicine researchers, working with scientists at the SLAC National Accelerator Laboratory, have made discoveries about the ways in which T cell receptors (shown in bright red) recognize invaders in the body. (Eric Smith and K. Christopher Garcia / Stanford University)

    X-ray studies at the Department of Energy’s SLAC National Accelerator Laboratory, combined with Stanford biological studies and computational analysis, revealed remarkable similarities in the structure of binding sites, which allow a given T cell to recognize many different invaders that provoke an immune response.

    t3
    T-cells use their receptors (red) to recognize different peptides (blue and yellow) presented on the surface of cells, a key mechanism to detect and combat infection. (Eric Smith and K. Christopher Garcia/Stanford University)

    t2
    This illustration shows the binding sites of a T-cell receptor (highlighted red) and a peptide (orange). Similarities in binding sites allow T-cells to bind to many different peptides. (Eric Smith and K. Christopher Garcia, Stanford University)

    The research demonstrates a faster, more reliable way to identify large numbers of antigens, the targets of the immune response, which could speed the discovery of disease treatments. It also may lead to a better understanding of what T cells recognize when fighting cancers and why they are triggered to attack healthy cells in autoimmune diseases such as diabetes and multiple sclerosis.

    “Until now, it often has been a real mystery which antigens T cells are recognizing; there are whole classes of disease where we don’t have this information,” said Michael Birnbaum, a graduate student who led the research at the School of Medicine in the laboratory of K. Christopher Garcia, the study’s senior author and a professor of molecular and cellular physiology and of structural biology.

    “Now it’s far more feasible to take a T cell that is important in a disease or autoimmune disorder and figure out what antigens it will respond to,” Birnbaum said.

    T cells are triggered into action by protein fragments, called peptides, displayed on a cell’s surface. In the case of an infected cell, peptide antigens from a pathogen can trigger a T cell to kill the infected cell. The research provides a sort of rulebook that can be used with high success to track down antigens likely to activate a given T cell, easing a bottleneck that has constrained such studies.

    Combination Approach

    In the study, researchers exposed a handful of mouse and human T-cell receptors to hundreds of millions of peptides, and found hundreds of peptides that bound to each type. Then they compiled and compared the detailed sequence – the order of the chemical building blocks – of the peptides that bound to each T-cell receptor.

    From that sample set, which represents just a tiny fraction of all peptides, a detailed computational analysis identified other likely binding matches. Researchers compared the 3-D structures of T cells and their unique receptors bound to different peptides at SLAC’s Stanford Synchrotron Research Lightsource (SSRL).

    “The X-ray work at SSRL was a key breakthrough in the study,” Birnbaum said. “Very different peptides aligned almost perfectly with remarkably similar binding sites. It took us a while to figure out this structural similarity was a common feature, not an oddity – that a vast number of unique peptides could be recognized in the same way.”

    Researchers also checked the sequencing of the peptides that were known to bind with a given T cell and found striking similarities there, too.

    “T-cell receptors are ‘cross-reactive,’ but in fairly limited ways. Like a multilingual person who can speak Spanish and French but can’t understand Japanese, a receptor can engage with a broad set of peptides related to one another,” Birnbaum said.

    Impact on Biomedical Science

    Finding out whether a given peptide activates a specific T-cell receptor has been a historically piecemeal process with a 20 to 30 percent success rate, involving burdensome hit-and-miss studies of biological samples. “This latest research provides a framework that can improve the success rate to as high as 90 percent,” Birnbaum said.

    “This is an important illustration of how SSRL’s X-ray-imaging capabilities allow researchers to get detailed structural information on technically very challenging systems,” said Britt Hedman, professor of photon science and science director at SSRL. “To understand the factors behind T-cell-receptor binding to peptides will have major impact on biomedical developments, including vaccine design and immunotherapy.”

    Additional contributors included the laboratories of Mark Davis, the Burt and Marion Avery Family Professor at Stanford School of Medicine, and Kai Wucherpfennig at the Dana Farber Cancer Institute and Harvard University. The research was supported by the National Institutes of Health and the Howard Hughes Medical Institute. SSRL is a scientific user facility supported by DOE’s Office of Science.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 1:25 pm on May 19, 2014 Permalink | Reply
    Tags: , , EBOLA, SLAC SSRL,   

    From SLAC Lab: “Fighting Ebola Virus Disease: ‘Transformer’ Protein Provides New Insights” 


    SLAC Lab

    May 15, 2014
    Manuel Gnida

    A new study reveals that a protein of the Ebola virus can transform into three distinct shapes, each with a separate function that is critical to the virus’s survival. Each shape offers a potential target for developing drugs against Ebola virus disease, a hemorrhagic fever that kills up to 9 out of 10 infected patients in outbreaks such as the current one in West Africa.

    eb
    VP40, a protein of the Ebola virus, can arrange itself into three very different shapes, shown in blue, each with a distinct function. (Nikola Stojanovic/SLAC and Zachary Bornholdt/The Scripps Research Institute)

    ebola
    Each of VP40’s structural arrangements is linked to a different function in the virus life cycle. While traveling inside infected cells, VP40 assumes a butterfly shape (top). Near the cell nucleus, VP40 transforms into a ring (bottom left) that regulates how the viral genetic information is copied. At the cell membrane, VP40 assembles into a linear structure (bottom right), which plays a role in the creation of new viruses. (Erica Ollmann Saphire and Zachary Bornholdt/The Scripps Research Institute)

    At SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and other X-ray facilities, a team led by Erica Ollmann Saphire of The Scripps Research Institute analyzed the structure of VP40, a protein best known for its role in creating and releasing new copies of the virus from infected cells.

    “The interesting thing about VP40 is that it does more than that,” Saphire says. “We found that it is multifunctional, with several essential roles for the virus.” The team reported its results in Cell.

    One Protein, Three Structures

    The team discovered that the protein can alter its shape, causing multiple copies of the protein to join up and create three very different assemblies: a butterfly shape composed of two, a ring formed by eight, and a linear structure built from six VP40 molecules. Prior to the study, only the protein ring was known.

    But what unique functions do the individual structures have? The researchers took the study to the next level by combining their X-ray data with additional biological experiments. “This approach allowed us to track not only where the different structures are located, but also what they do inside the cell,” Saphire says.

    It turns out that the function of each structure is linked to a specific stage of the virus life cycle.

    While moving around inside infected cells, VP40 assumes the butterfly shape.

    In the early stages of an infection, the VP40 molecules change their structure and assemble into a ring near the cell nucleus, regulating how the virus’s genetic information is copied.

    In the later stages, VP40 travels to the cell’s outer layer, or membrane, and transforms into its linear structure, which plays a crucial role in the creation of new copies of the virus.

    The transformational changes of VP40 update the nearly 60-year-old “central dogma of biology,” which implies that a given gene typically makes a single protein with a single 3-D shape. “Our findings open the central dogma wide up,” says Saphire, who suggests that structural rearrangements as seen in VP40 may be more common than previously thought.

    From an evolutionary perspective, structural diversity has developed out of necessity. Unlike humans, who possess some 20,000 protein-encoding genes, the Ebola virus must get by with a drastically smaller number.

    “The Ebola virus has only seven genes. However, its proteins must serve many more functions than that,” explains Scripps researcher Zachary Bornholdt, the study’s first author. “Protein transformability allows the virus to make the most out of very little.”

    Potential Drug Targets

    All three functions of VP40 – traveling inside infected cells, regulating genetic information and creating new viruses – are essential to the Ebola virus, and disrupting any of the corresponding structures or their transformations would severely affect it. Therefore, VP40’s triple role provides researchers with important clues for the development of potential antiviral drugs.

    “The more we are able to define VP40’s structures and functions, the more we can expand what we can do with this information,” Bornholdt says. “Our data suggest, for instance, that it might be more effective to target the ring than the other structures because only a small fraction of all VP40 molecules form the ring in the course of the viral life cycle.”

    Although a cure for Ebola virus disease is still remote, the new study already has practical applications: The same VP40 proteins produced for this study are being used in test strips to identify the disease in patients affected by the current outbreak in West Africa.

    The research team included scientists from The Scripps Research Institute and the University of Wisconsin-Madison in the U.S., as well as from the University of Tokyo and the Exploratory Research for Advanced Technology Program in Japan. Part of the research was performed at SSRL’s microbeam facility for crystallography (Beam Line 12-2). The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 12:57 pm on May 15, 2014 Permalink | Reply
    Tags: , , SLAC SSRL,   

    From SLAC Lab: “Exploring Heat and Energy at the Smallest Scales” 


    SLAC Lab

    May 14, 2014
    Glenn Roberts Jr.

    Special low-alpha operating period enables precise measurement of changes in material

    In a recent experiment at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), scientists “tickled” atoms to explore the flow of heat and energy across materials at ultrasmall scales. The experiment, detailed in the May 6 edition of Structural Dynamics, enabled them to see subtle light-driven changes in the atomic structure of thin materials, relevant to thermoelectric and electronic devices.

    “These results show that we can really follow the flow of energy across nanoscale devices, and resolve the dynamics in a way that hasn’t been possible before. It opens the door to new, more efficient types of devices,” said research team member Aaron Lindenberg, an assistant professor at SLAC and Stanford affiliated with the Stanford PULSE Institute and the Stanford Institute for Materials and Energy Sciences [SIMES].

    Striking superthin materials with specially timed X-ray and laser pulses fired at a rate of more than one million times per second, scientists caused atoms to vibrate and measured their movement with accuracy down to a fraction of a femtometer, which is a billion-billionth of a meter.

    “We were able to see remarkably small structural changes that we had never envisioned we could,” said Michael Kozina, a graduate student with the Stanford PULSE Institute, a joint institute of SLAC and Stanford, who led the research.

    Researchers observed a longer-than-expected time delay, measured at about a billionth of a second, in the transfer of heat from the thin films to the surface below.

    The cause of this delay has important implications for materials research, Kozina said. “In electronic devices, you want to dissipate the heat as fast as you can, and in thermoelectric devices you want to maintain that delay as long as you can and prevent heat from flowing rapidly,” he added. “Now we have a way to directly look at this.”

    laser
    An optical laser casts a green glow during a low-alpha-mode experiment at SSRL. (Aaron Lindenberg/SLAC)

    ssrl
    A view of a materials science experimental setup at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL). The circular instrument that frames this photo is part of a diffractometer that was used to align samples and a detector with X-rays. The metallic cylinders are motors used to align the samples. The blue box is one of the X-ray detectors used in the experiment. (Mike Kozina/SLAC)

    The response of the materials to the rapid-fire laser pulses, which was too fast to be measured for each individual pulse, was averaged out over time.

    The experiment was performed during a series of special operating periods at SSRL known as low-alpha mode, in which the accelerator ring that feeds X-rays to SSRL experiments is tuned to produce shorter-than-usual pulses, measured in trillionths of a second, and its electric current is dialed down. SSRL is one of just a few synchrotrons in the world to run in low-alpha mode.

    lode
    An optical laser interacts with a thin-film material in an experiment at SLAC’s Stanford Synchrotron Radiation Lightsource. The circular instrument is part of an X-ray diffractometer, and the bright light toward the middle of the photo is a view of the laser light striking the sample. The other bright spot in this image, at upper left, is produced by laser light glaring on an X-ray detector. In this experiment, laser pulses were synchronized with rapid-fire X-ray pulses to study very slight atomic-scale changes in samples. (Mike Kozina/SLAC)

    “Short-pulse research is an important component in SSRL’s science strategy and provides capabilities that are complementary to the Linac Coherent Light Source,” SLAC’s X-ray laser, said Piero Pianetta, acting director of SSRL.

    green
    Green laser light is visible in an experimental setup at SLAC’s SSRL. Infared laser light was “frequency-doubled” to produce this green laser light. The large apparatus on the left is an X-ray diffractometer that was used to align the sample and detector with X-rays. (Mike Kozina/SLAC)

    Kozina said low-alpha-mode experiments are complementary to other research the group has conducted at LCLS and using other tools, because they allow researchers to probe very slight processes in materials and don’t require jarring the material with higher-energy pulses to get a measurable response. “It’s like the difference between tickling the atomic structure in the samples versus hitting it with a hammer,” he said.

    The findings from this experiment, which explored films of bismuth, bismuth ferrite and PZT (a blend containing lead, zirconium and titanium) measuring just billionths of an inch thick, mark the first journal-published scientific results obtained during low-alpha-mode operations at SSRL.

    A next step in the research is to study different alignments of the samples with respect to the surface they rest on to measure whether those changes slow or speed the transfer of heat and charge, Kozina said.

    SSRL has three scheduled periods each year, each spanning a few days, for low-alpha mode, and Kozina said that the latest research is the culmination of a handful of experimental runs over the course of several years. “Incremental successes have finally reached the threshold of experimental success,” he said, “The goal is to make this operating mode more turn-key and open it up to visiting researchers.”

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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  • richardmitnick 4:08 pm on April 25, 2014 Permalink | Reply
    Tags: , , , , SLAC SSRL   

    From SLAC Lab: “Scientists Watch High-temperature Superconductivity Emerge out of Magnetism” 

    SLAC Lab

    April 24, 2014
    Glennda Chui

    Like Dancers at a Party, Electrons Pair Up a Few at a Time to Effortlessly Conduct Electricity

    Scientists at SLAC National Accelerator Laboratory and Stanford University have shown for the first time how high-temperature superconductivity emerges out of magnetism in an iron pnictide, a class of materials with great potential for making devices that conduct electricity with 100 percent efficiency.

    In experiments at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), the team “doped” the material – one of two known types of high-temperature superconductor – by adding or subtracting electrons to enhance its superconducting abilities. Then they used a beam of ultraviolet light to measure changes in the material’s electronic behavior as it was chilled to a temperature where superconductivity becomes possible.

    levityation
    Superconducting materials expel magnetic fields, whose repulsive force can levitate a magnet, as shown here. Nevertheless, studies have shown superconductivity and magnetism can coexist in the same material. Now SLAC and Stanford researchers show that the two phases are interwoven at a very fine, microscopic level in a type of high-temperature superconductor known as an iron pnictide, and reveal how one phase gives way to the other. (Julien Bobroff, Frederic Bouquet and Jeffrey Quilliam/Laboratory of Solid State Physics, LPS, via Wikimedia Commons)

    The researchers saw the two states battle for dominance: At first the electrons in the material all lined up with their spins pointed in specific directions, a hallmark of magnetism. But as the temperature dropped, a few electrons paired up, like dancers at a party, to effortlessly conduct electricity; then a few more; until finally all the active electrons found partners and the material was fully superconducting, a much more complex behavior.

    The results, published April 25 in Nature Communications, are an important step toward understanding how high-temperature superconductors work – information scientists need to realize their dream of engineering superconductors with more useful properties that operate at close to room temperature for a variety of practical applications.

    Complexity Emerges from Simple Ingredients

    “For a while both magnetism and superconductivity co-exist; that’s not a surprise,” said Ming Yi, a graduate student with the Stanford Institute for Materials and Energy Sciences (SIMES) and lead author of the report. “But we wanted to see how just these two phases interact with each other. Now we finally have the high-resolution tools we need to see these changes at a microscopic level, and we find that the same electrons that were participating in the magnetic order have switched over to participate in the superconducting order. These two orders compete for the same electrons.’’

    Comparing their experimental data to the results of simulations, the researchers determined that the magnetism and superconductivity in iron pnictide were interwoven at a very fine, microscopic level, rather than occupying larger, separate puddles within the material. The simulations were led by theorists Lex Kemper of Lawrence Berkeley National Laboratory, Stanford graduate student Nachum Plonka and SIMES Director Thomas Devereaux.

    “This is a beautiful example of ‘emergence,’ in which simple ingredients give rise to complex behavior,” said co-author Zhi-Xun Shen, a professor at SLAC and Stanford and SLAC’s advisor for science and technology. “Emergence is a major theme of modern research on organizing principles of nature,” he said. “Our hope is that research on quantum systems like this one, which are very simple model systems, will eventually give us insights into such organizing principles.”

    Exploring a Mystery Material

    Discovered in 1986, high-temperature superconductors carry electricity without any loss at much warmer temperatures than conventional superconductors, which have to be chilled to at least 30 kelvins (minus 243 degrees Celsius). Still, scientists have not been able to get high-temperature superconductors to operate above minus 138 degrees Celsius.

    While these materials have the potential to save money and energy in a number of applications, from carrying electricity over long-distance power lines to operating maglev trains, the high cost and logistics of keeping them cold and their difficult-to-handle properties have held them back.

    As in regular superconductors, electrons in high-temperature superconductors form pairs to conduct current. But the mechanism behind this pairing in the high-temperature materials – the “glue” that holds the electrons together – is still unknown, said Donghui Lu, a senior staff scientist at SSRL and one of the principal investigators for the study.

    Another mystery: In theory, superconductivity and magnetism are not supposed to co-exist; the presence of one should drive out the other. But previous studies have shown they can in fact exist in the same material, and scientists have been eager to learn the details of how and why that happens.

    While this study doesn’t answer those burning questions, it does give scientists a closer look at the details of what happens as superconductivity emerges.

    The results may also shed light on the other known family of high-temperature superconductors, the copper-based cuprates, the scientists wrote, and comparing results from the two may lead to “an eventual understanding of the mechanism of unconventional superconductivity.”

    In addition to SLAC and SIMES, which is a joint SLAC/Stanford institute, researchers from Stanford University, Lawrence Berkeley National Laboratory, Nanjing University, and the University of California-Berkeley contributed to this work. Some measurements were carried out at Berkeley Lab’s Advanced Light Source. The work at Stanford, SLAC and the Advanced Light Source was funded by the U.S. Department of Energy Office of Science.

    See the full article here.

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
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