Sandia hosting national conversation on engineering

Sandia Labs News Releases

May 28, 2013

Sandia hosting national conversation on engineering

Sandia President and Laboratories Director Paul Hommert will be among the leaders opening a National Engineering Forum in Albuquerque on Wednesday, May 29. The forum is the second in a series of regional dialogues scheduled this year in cities that have played a role in shaping engineering in the United States. (Photo by Randy Montoya) Click the thumbnail for a high-resolution image.

ALBUQUERQUE, N.M. — Sandia President and Laboratories Director Paul Hommert says U.S. prosperity depends on effective use of engineering to turn scientific innovation into products that come rapidly to market and increasingly are made in the U.S.A.

The National Engineering Forum (NEF) and Sandia are bringing together regional leaders for a conversation about engineering on Wednesday, May 29, in Albuquerque. The event will help identify what the nation’s engineering community can do to make sure technical talent will be available in the future, prepare engineers for the 21^st century and secure U.S. leadership in a global economy that’s increasingly focused on innovation.

Media representatives are invited to attend the invitation-only NEF event at 6 p.m. on Wednesday, May 29, at theNational Museum of Nuclear Science & History, 601 Eubank Blvd. SE. Sandia President and Laboratories Director Paul Hommert, Lockheed Martin Senior Vice President and Chief Technology Officer Ray O. Johnson, Lockheed Martin Vice President for Engineering Jeff Wilcox and Council on Competitiveness President and CEO Deborah L. Wince-Smith will speak at the NEF regional dialogue dinner. Contact Sue Holmes at (505) 844-6362 or sholmes@sandia.govby 2 p.m. Wednesday.

“Publicly funded research at Sandia National Laboratories benefits the nation in countless ways. Our multidisciplinary scientists and engineers solve complex problems, address issues of national and even global importance and translate basic science into technological discovery and innovation that strengthens U.S. competitiveness,” Hommert said before the forum.

The event is the second in a series of regional dialogues scheduled this year in cities that have played a prominent role in shaping engineering in the nation. The forums will culminate next year with a gathering in Washington, D.C., to bring together leaders and ideas from the regional events to emphasize the importance of engineering to the nation’s economic security.

The NEF brings together industry executives, academics, policymakers, engineering groups and others concerned about sustaining engineering in the United States and its impact on the nation’s security and prosperity. Lockheed Martin Corp., the Council on Competitiveness and the National Academy of Engineering launched the National Engineering Forum in 2012.

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Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin company, for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies and economic competitiveness.

Models from Big Molecules Captured in a Flash

Berkeley Lab researchers and their colleagues create a new way to model biological molecules caught with a flash of x-rays

MAY 26, 2013

Paul Preuss 510-486-6249  paul_preuss@lbl.gov

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News Release

Fluctuation x-ray scattering is the basis of a new technique for rapidly modeling the shapes of large biological models, here demonstrated (gray envelopes) using existing diffraction data superposed on known high-resolution structures. Top left, lysine-arginine-ornithine (LAO) binding protein; top right, lysozome; bottom left, peroxiredoxin; and, bottom right, Satellite Tobacco Mosaic Virus (STMV).

To learn how biological molecules like proteins function, scientists must first understand their structures. Almost as important is understanding how the structures change, as molecules in the native state do their jobs.
Existing methods for solving structure largely depend on crystallized molecules, and the shapes of more than 80,000 proteins in a static state have been solved this way. The majority of the two million proteins in the human body can’t be crystallized, however. For most of them, even their low-resolution structures are still unknown.
Their chance to shine may have come at last, thanks to new techniques developed by Peter Zwart and his colleagues at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), working with collaborators from Arizona State University, the University of Wisconsin-Milwaukee, and DOE’s Pacific Northwest National Laboratory (PNNL). The new method promises a more informative look at large biological molecules in their native, more fluid state.
The researchers describe their results in two recent papers in Foundations of Crystallography and in Physical Review Letters.
Diffraction before destruction
A key factor in new ways of looking at biomolecules is the data created by free-electron lasers (FELs) such as the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory, whose powerful x‑ray pulses are measured in quadrillionths of a second. These pulses are faster than a molecule can rotate, and the experimental data reflects the state of the molecule frozen in time.
“It’s a technique called ‘diffract before destroy,’ because the data is collected before the particle literally blows apart,” says Zwart, a member of the Lab’s Physical Biosciences Division, and the science lead for the Berkeley Center for Structural Biology at the Advanced Light Source. “FELs have shown they can derive structures from single particles, each hit with a single pulse, but there are major challenges to this approach.”
Instead of single particles, Zwart and his colleagues include many particles in each shot. When analyzed by computer programs, the data from the different diffraction patterns can be combined to provide detailed insights into the structures the molecules adopt in solution.

At left, numerous copies of a molecule in solution are fired across the x-ray beam of a free-electron laser. Diffraction patterns are collected just before the femtosecond x-ray pulses explode the particles. At right, a 3D model is constructed by repeatedly enlarging and removing parts of an arbitrary shape until it closely matches the average values derived from the diffraction patterns.

The technique is called fluctuation x-ray scattering (fXS), and Zwart and his colleagues have shown that data obtained this way with free-electron lasers can yield low-resolution shapes of biomolecules in close to their natural state, with much greater confidence than is currently possible with less powerful synchrotron light sources.
“Our algorithm starts with a trial model and modifies it by randomly adding or subtracting volume until the shape of the model achieves the optimum fit with the data,” Zwart says. This trial-and-error optimization technique, tested on known configurations at the LCLS, can resolve the shapes of individual macromolecules with fXS data alone.
It’s not only the structures of molecules taken one at a time that can be solved this way. Zwart and his former postdoc Gang Chen, working with Dongsheng Li of PNNL, have shown that data from mixtures of different kinds of molecules can be untangled to provide clues on the structure of the individual components, forming a basis for understanding the dynamic behavior of large biological molecules working together in solution.
By understanding their structural changes, Zwart and his colleagues are developing fluctuation x-ray scattering as an indispensable tool for determining how mixtures of different proteins behave independently or in concert.

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“Three-dimensional single-particle imaging using angular correlations from X-ray laser data,” by Haiguang Liu, Billy K. Poon, Dilano K. Saldin, John C. H. Spence, and Peter H. Zwart, appears in the July 2013 issue of Foundations of Crystallography and is available online athttp://journals.iucr.org/a/issues/2013/04/00/issconts.html.
“Component particle structure in heterogeneous disordered ensembles extracted from high-throughput fluctuation x-ray scattering,” by Gang Chen, Peter H. Zwart, and Dongsheng Li, appears in the 10 May 2013 edition of Physical Review Letters, and is available online at http://prl.aps.org/abstract/PRL/v110/i19/e195501.
This work was supported by DOE’s Office of Science through Laboratory Directed Research and Development programs at Berkeley Lab and PNNL; the international Human Frontier Science Program; the National Science Foundation; the University of Wisconsin Research Growth Initiative; and the Chinese Academy of Sciences.
Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit www.lbl.gov.
DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit the Office of Science website atscience.energy.gov.

TAGS: Advanced Light Source, computational research, physical biosciences

Copper on the Brain

MAY 24, 2013

Lynn Yarris (510) 486-5375  lcyarris@lbl.gov

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Science Short

Copper Sensor-3 (CS3), a small-molecule fluorescent probe, was used to map the movement of copper in the brain triggered by neuronal activity.

The value of copper has risen dramatically in the 21^st century as many a thief can tell you, but in addition to the thermal and electrical properties that make it such a hot commodity metal, copper has chemical properties that make it essential to a healthy brain. Working at the interface of chemistry and neuroscience, Berkeley Lab chemist Christopher Chang and his research group at UC Berkeley have developed a series of fluorescent probes for molecular imaging of copper in the brain. Speaking at the recent national meeting of the American Chemical Society in New Orleans, he described the challenges of creating and applying live-cell and live-animal copper imaging probes and explained the importance of meeting these challenges.
“The human brain is a unique biological system, possessing unparalleled biological complexity in a compact space,” Chang said. “Although it accounts for only two-percent of total body mass, it consumes 20-percent of the oxygen taken in through respiration. As a consequence of its high demand for oxygen and oxidative metabolism, the brain has among the highest levels of copper, as well as iron and zinc in the body.”
Neuron and glia cells in the brain both require copper for the basic respiratory and antioxidant enzymes cytochrome c oxidase and superoxide dismutase. Copper is also necessary for brain-specific enzymes that control neurotransmitters, such as dopamine, as well as neuropeptides and dietary amines. Disruption of copper oxidation in the brain has been linked to several neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Menkes’ and Wilson’s.

Christopher Chang is a chemist who holds joint appointments with Berkeley Lab and UC Berkeley and is also an investigator with the Howard Hughes Medical Institute. (Photo by Roy Kaltschmidt)

“The complex relationships between copper status and various stages of health and disease have been difficult to determine in part because of a lack of methods for monitoring dynamic changes in copper pools in whole living organisms,” Chang said. “We’ve been designing fluorescent probes that can map the movement of copper in live cells, tissue or even model organisms, such as mice and zebrafish.”
Their first success was Coppersensor-3 (CS3), a small-molecule fluorescent probe that can be used to image labile copper pools in living cells at endogenous, basal levels. They used CS3 in conjunction with synchrotron-based X-ray fluorescence microscopy (XRFM) to discover that neuronal cells move significant pools of copper upon activation and that these copper movements are dependent on calcium signaling.
“This was the first established link between mobile copper and major cell signaling pathways,” Chang said. “Being able to map transient copper movements after neuronal depolarization revealed how neural activity triggers copper mobility, and enabled us to create a model for calcium/copper crosstalk in neurons.”
The CS3 probe was followed by Mitochondrial Coppersensor-1 (Mito-CS1), a fluorescent sensor that can selectively target mitochondria and detect basal and labile copper pools in living cells. Mitochondria, the organelles that generate most of the chemical energy used by cells, are important reservoirs for copper. By allowing direct, real-time visualization of exchangeable mitochondrial copper pools, the Mito-CS1 probe enabled Chang and his colleagues to discover that cells maintain copper homeostasis in mitochondria even in situations of copper deficiency and metabolic malfunctions.
“This work illustrated the importance of regulating copper stores in mitochondria,” Chang said.
The latest copper probe from Chang’s group is Coppersensor 790 (CS790), a fluorescent sensor that features near-infrared excitation and emission capabilities, ideal for penetrating thicker biological specimens. CS790 can be used to monitor fluctuations in exchangeable copper stores under basal conditions, as well as under copper overload or deficiency conditions. Chang and his group are using CS790 to study a mouse model of Wilson’s disease, a genetic disorder characterized by an accumulation of excess copper.
“The in vivo fluorescence detection of copper provided by CS790 and our other fluorescent probes is opening up unique opportunities to explore the roles that copper plays in the healthy physiology of the brain, as well as in the development and progression copper-related diseases,” Chang said.
For more information about the research of Christopher Chang, visit his Website here

TAGS: biochemistry, bioimaging, biology, medical

Research effort deep underground could sort out cosmic-scale mysteries

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Media Contact: Bill Cabage Communications and Media Relations 865.574.4399 Secondary Contact: Joshua Haston Communications and Media Relations 865.574.4160

Research effort deep underground could sort out cosmic-scale mysteries

	The Majorana Demonstrator is being assembled and stored 4,850 feet beneath the earth's surface in enriched copper to limit the amount of background interference from cosmic rays and radioactive isotopes. (hi-res image)

OAK RIDGE, Tenn., May 23, 2013 — The Department of Energy's Oak Ridge National Laboratory has begun delivery of germanium-76 detectors to an underground laboratory in South Dakota in a team research effort that might explain the puzzling imbalance between matter and antimatter generated by the Big Bang.

"It might explain why we're here at all," said David Radford, who oversees specific ORNL activities in the Majorana Demonstrator research effort. "It could help explain why the matter that we are made of exists."

Radford, a researcher in ORNL's Physics Division and an expert in germanium detectors, has been delivering germanium-76 to Sanford Underground Research Laboratory (SURF) in Lead, S.D., for the project. After navigating a Valentine's Day blizzard on the first two-day drive from Oak Ridge, Radford made a second delivery in March.

ORNL serves as the lead laboratory for the Majorana Demonstrator research effort, a collaboration of research institutions representing the United States, Russia, Japan and Canada. The project is managed by the University of North Carolina's Prof. John Wilkerson, who also has a joint faculty appointment with ORNL.

Research at SURF is being conducted 4,850 feet beneath the earth's surface with the intention of building a 40-kilogram germanium detector, capable of detecting the theorized neutrinoless double beta decay. Detection might help to explain the matter-antimatter imbalance.

Before the detection of the unobserved decay can begin, however, the germanium must first be processed, refined and enriched. Radford coordinated the multistep process, which includes an essential pit stop in Oak Ridge.

The 42.5 kilograms of 86-percent enriched white germanium oxide powder required for the project is valued at $4 million and was transported from a Russian enrichment facility to a secure underground ORNL facility in a specially designed container. The container's special shielding and underground storage limited exposure of the germanium to cosmic rays.

Without such preventative measures, Radford says, "Cosmic rays transmute germanium atoms into long-lived radioactive atoms, at the rate of about two atoms per day per kilogram of germanium. Even those two atoms a day will add to the background in our experiment. So we use underground storage to reduce the exposure to cosmic rays by a factor of 100."

The germanium must further undergo a reduction and purification process at two Oak Ridge companies, Electrochemical Systems, Inc. (ESI) and Advanced Measurement Technology (AMETEK), before being moved to its final destination in South Dakota. ESI works to reduce the powdered germanium oxide to metal germanium bars. ORTEC, a division of AMETEK, further purifies the bars, using the material to grow large single crystals of germanium, and turning those into one-kilogram cylindrical germanium detectors that will be used in the Demonstrator. Once they leave AMETEK, Radford and his team transport the detectors to SURF.

The enrichment process is lengthy. The Majorana Demonstrator project began the partnership with ESI four years ago. To date, ORNL has delivered -- via Radford's two trips -- nine of the enriched detectors, which are valued at about $2 million including the original cost of the enriched germanium oxide powder.

Requiring a total of 30 enriched detectors, the Majorana Demonstrator is not expected to be fully complete and operational until 2015.

Those involved in the Majorana research effort believe its completion and anticipated results will help pave the way for a next-generation detector using germanium-76 with unprecedented sensitivity. The future one-ton detector will help to determine the ratio and masses of conserved and annihilated lepton particles that are theorized to cause the initial imbalance of matter and antimatter from the Big Bang.

"The research effort is the first major step towards building a one-ton detector - a potentially Nobel-Prize-worthy project," Radford says.

ORNL's partner institutions in the Majorana Demonstration Project are Black Hills State University, Duke University, Institute for Theoretical and Experimental Physics (Russia), Joint Institute for Nuclear Research (Russia), Los Alamos National Laboratory, Lawrence Berkeley National Laboratory, North Carolina State University, Osaka (Japan) University, Pacific Northwest National Laboratory, South Dakota School of Mines and Technology, Triangle Universities Nuclear Laboratory, Centre for Particle Physics (Canada), University of Chicago, University of North Carolina, University of South Carolina, University of South Dakota, University of Tennessee and the Center for Experimental Nuclear Physics and Astrophysics.

The Majorana Demonstrator research project is funded by the National Science Foundation and the Department of Energy's Office of Nuclear Physics.

ORNL is managed by UT-Battelle for the Department of Energy's Office of Science. DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visithttp://science.energy.gov.