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  • richardmitnick 12:37 pm on February 21, 2019 Permalink | Reply
    Tags: "Big Data at the Atomic Scale: New Detector Reaches New Frontier in Speed", A new detector that can capture atomic-scale images in millionths-of-a-second increments., , , Electron Microscopy, known as the “4D Camera” (for Dynamic Diffraction Direct Detector), , , NCEM-National Center for Electron Microscopy, The Molecular Foundry, The new detector, The Transmission Electron Aberration-corrected Microscope (TEAM 0.5) at Berkeley Lab   

    From Lawrence Berkeley National Lab: “Big Data at the Atomic Scale: New Detector Reaches New Frontier in Speed” 

    Berkeley Logo

    From Lawrence Berkeley National Lab

    February 21, 2019
    Glenn Roberts Jr.
    geroberts@lbl.gov
    (510) 486-5582

    1
    The Transmission Electron Aberration-corrected Microscope (TEAM 0.5) at Berkeley Lab has been upgraded with a new detector that can capture atomic-scale images in millionths-of-a-second increments. (Credit: Thor Swift/Berkeley Lab)


    This video provides an overview of the R&D effort to upgrade an electron microscope at Berkeley Lab’s Molecular Foundry with a superfast detector, the 4D Camera. The detector, which is linked to a supercomputer at Berkeley Lab via a high-speed data connection, can capture more images at a faster rate, revealing atomic-scale details across much larger areas than was possible before. (Credit: Marilyn Chung/Berkeley Lab)

    Advances in electron microscopy – using electrons as imaging tools to see things well beyond the reach of conventional microscopes that use light – have opened up a new window into the nanoscale world and brought a wide range of samples into focus as never before.

    Electron microscopy experiments can only use a fraction of the possible information generated as the microscope’s electron beam interacts with samples. Now, a team at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has designed a new kind of electron detector that captures all of the information in these interactions.

    This new tool, a superfast detector installed Feb. 12 at Berkeley Lab’s Molecular Foundry, a nanoscale science user facility, captures more images at a faster rate, revealing atomic-scale details across much larger areas than was possible before. The Molecular Foundry and its world-class electron microscopes in the National Center for Electron Microscopy (NCEM) provide access to researchers from around the world.

    Faster imaging can also reveal important changes that samples are undergoing and provide movies vs. isolated snapshots. It could, for example, help scientists to better explore working battery and microchip components at the atomic scale before the onset of damage.

    The detector, which has a special direct connection to the Cori supercomputer at the Lab’s National Energy Research Scientific Computing Center (NERSC), will enable scientists to record atomic-scale images with timing measured in microseconds, or millionths of a second – 100 times faster than possible with existing detectors.

    NERSC Cray Cori II supercomputer at NERSC at LBNL, named after Gerty Cori, the first American woman to win a Nobel Prize in science

    “It is the fastest electron detector ever made,” said Andrew Minor, NCEM facility director at the Molecular Foundry.

    “It opens up a new time regime to explore with high-resolution microscopy. No one has ever taken continuous movies at this time resolution” using electron imaging, he said. “What happens there? There are all kinds of dynamics that might happen. We just don’t know because we’ve never been able to look at them before.” The new movies could reveal tiny deformations and movements in materials, for example, and show chemistry in action.

    The development of the new detector, known as the “4D Camera” (for Dynamic Diffraction Direct Detector), is the latest in a string of pioneering innovations in electron microscopy, atomic-scale imaging, and high-speed data transfer and computing at Berkeley Lab that span several decades.

    “Our group has been working for some time on making better detectors for microscopy,” said Peter Denes, a Berkeley Lab senior scientist and a longtime pioneer in the development of electron microscopy tools.

    “You get a whole scattering pattern instead of just one point, and you can go back and reanalyze the data to find things that maybe you weren’t focusing on before,” Denes said. This quickly produces a complete image of a sample by scanning across it with an electron beam and capturing information based on the electrons that scatter off the sample.

    Mary Scott, a faculty scientist at the Molecular Foundry, said that the unique geometry of the new detector allows studies of both light and heavyweight elements in materials side by side. “The reason you might want to perform one of these more complicated experiments would be to measure the positions of light elements, particularly in materials that might be really sensitive to the electron beam – like lithium in a battery material – and ideally you would be able to also precisely measure the positions of heavy elements in that same material,” she said.

    The new detector has been installed on the Transmission Electron Aberration-corrected Microscope 0.5 (TEAM 0.5) at the Molecular Foundry, which set high-resolution records when it launched at NCEM a decade ago and allows visiting researchers to access single-atom resolution for some samples. The detector will generate a whopping 4 terabytes of data per minute.

    “The amount of data is equivalent to watching about 60,000 HD movies simultaneously,” said Peter Ercius, a staff scientist at the Molecular Foundry who specializes in 3D atomic-scale imaging.

    Brent Draney, a networking architect at Berkeley Lab’s NERSC, said that Ercius and Denes had approached NERSC to see what it would take to build a system that could handle this huge, 400-gigabit stream of data produced by the 4D Camera.

    His response: “We actually already have a system capable of doing that. What we really needed to do is to build a network between the microscope and the supercomputer.”

    2
    A technician works on the TEAM 0.5 microscope. The microscope has been upgraded with a superfast detector called the 4D Camera that can capture atomic-scale images in millionths-of-a-second increments. (Credit: Thor Swift/Berkeley Lab)

    Camera data is transferred over about 100 fiber-optic connections into a high-speed ethernet connection that is about 1,000 times faster than the average home network, said Ian Johnson, a staff scientist in Berkeley Lab’s Engineering Division. The network connects the Foundry to the Cori supercomputer at NERSC.

    Berkeley Lab’s Energy Sciences Network (ESnet), which connects research centers with high-speed data networks, participated in the effort.

    Ercius said, “The supercomputer will analyze the data in about 20 seconds in order to provide rapid feedback to the scientists at the microscope to tell if the experiment was successful or not.”

    Jim Ciston, another Molecular Foundry staff scientist, said, “We’ll actually capture every electron that comes through the sample as it’s scattered. Through this really large data set we’ll be able to perform ‘virtual’ experiments on the sample – we won’t have to go back and take new data from different imaging conditions.”

    The work on the new detector and its supporting data systems should benefit other facilities that produce high volumes of data, such as the Advanced Light Source and its planned upgrade, and the LCLS-II project at SLAC National Accelerator Laboratory, Ciston noted.

    LBNL Advanced Light Source

    SLAC LCLS-II

    The Advanced Light Source, ESnet, Molecular Foundry, and NERSC are DOE Office of Science User Facilities.

    The development of the 4D Camera was supported by the Accelerator and Detector Research Program of the Department of Energy’s Office of Basic Energy Sciences, and work at the Molecular Foundry was supported by the DOE’s Office of Basic Energy Sciences.

    3
    This computer chip is a component in a superfast detector called the 4D Camera. The detector is an upgrade for a powerful electron microscope at Berkeley Lab’s Molecular Foundry. (Credit: Marilyn Chung/Berkeley Lab)

    See the full article here .

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    Bringing Science Solutions to the World

    In the world of science, Lawrence Berkeley National Laboratory (Berkeley Lab) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the National Academy of Sciences (NAS), one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the National Academy of Engineering, and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

    Berkeley Lab is a member of the national laboratory system supported by the U.S. Department of Energy through its Office of Science. It is managed by the University of California (UC) and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above the UC Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

    Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a UC Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

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

    University of California Seal

    DOE Seal

     
  • richardmitnick 10:13 am on January 8, 2019 Permalink | Reply
    Tags: , , Electron Microscopy, Infrared spectroscopy, , , ,   

    From SLAC National Accelerator Lab: “Study shows single atoms can make more efficient catalysts” 

    From SLAC National Accelerator Lab

    January 7, 2019
    Glennda Chui

    1
    Scientists used a combination of four techniques, represented here by four incoming beams, to reveal in unprecedented detail how a single atom of iridium catalyzes a chemical reaction. (Greg Stewart/SLAC National Accelerator Laboratory)

    Detailed observations of iridium atoms at work could help make catalysts that drive chemical reactions smaller, cheaper and more efficient.

    Catalysts are chemical matchmakers: They bring other chemicals close together, increasing the chance that they’ll react with each other and produce something people want, like fuel or fertilizer.

    Since some of the best catalyst materials are also quite expensive, like the platinum in a car’s catalytic converter, scientists have been looking for ways to shrink the amount they have to use.

    Now scientists have their first direct, detailed look at how a single atom catalyzes a chemical reaction. The reaction is the same one that strips poisonous carbon monoxide out of car exhaust, and individual atoms of iridium did the job up to 25 times more efficiently than the iridium nanoparticles containing 50 to 100 atoms that are used today.

    The research team, led by Ayman M. Karim of Virginia Tech, reported the results in Nature Catalysis.

    “These single-atom catalysts are very much a hot topic right now,” said Simon R. Bare, a co-author of the study and distinguished staff scientist at the Department of Energy’s SLAC National Accelerator Laboratory, where key parts of the work took place. “This gives us a new lens to look at reactions through, and new insights into how they work.”

    Karim added, “To our knowledge, this is the first paper to identify the chemical environment that makes a single atom catalytically active, directly determine how active it is compared to a nanoparticle, and show that there are very fundamental differences – entirely different mechanisms – in the way they react.”

    Is smaller really better?

    Catalysts are the backbone of the chemical industry and essential to oil refining, where they help break crude oil into gasoline and other products. Today’s catalysts often come in the form of nanoparticles attached to a surface that’s porous like a sponge – so full of tiny holes that a single gram of it, unfolded, might cover a basketball court. This creates an enormous area where millions of reactions can take place at once. When gas or liquid flows over and through the spongy surface, chemicals attach to the nanoparticles, react with each other and float away. Each catalyst is designed to promote one specific reaction over and over again.

    But catalytic reactions take place only on the surfaces of nanoparticles, Bare said, “and even though they are very small particles, the expensive metal on the inside of the nanoparticle is wasted.”

    Individual atoms, on the other hand, could offer the ultimate in efficiency. Each and every atom could act as a catalyst, grabbing chemical reactants and holding them close together until they bond. You could fit a lot more of them in a given space, and not a speck of precious metal would go to waste.

    Single atoms have another advantage: Unlike clusters of atoms, which are bound to each other, single atoms are attached only to the surface, so they have more potential binding sites available to perform chemical tricks – which in this case came in very handy.

    Research on single-atom catalysts has exploded over the past few years, Karim said, but until now no one has been able to study how they function in enough detail to see all the fleeting intermediate steps along the way.

    Grabbing some help

    To get more information, the team looked at a simple reaction where single atoms of iridium split oxygen molecules in two, and the oxygen atoms then react with carbon monoxide to create carbon dioxide.

    They used four approaches­ – infrared spectroscopy, electron microscopy, theoretical calculations and X-ray spectroscopy with beams from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) – to attack the problem from different angles, and this was crucial for getting a complete picture.

    SLAC/SSRL

    SLAC SSRL Campus

    “It’s never just one thing that gives you the full answer,” Bare said. “It’s always multiple pieces of the jigsaw puzzle coming together.”

    The team discovered that each iridium atom does, in fact, perform a chemical trick that enhances its performance. It grabs a single carbon monoxide molecule out of the passing flow of gas and holds onto it, like a person tucking a package under their arm. The formation of this bond triggers tiny shifts in the configuration of the iridium atom’s electrons that help it split oxygen, so it can react with the remaining carbon monoxide gas and convert it to carbon dioxide much more efficiently.

    More questions lie ahead: Will this same mechanism work in other catalytic reactions, allowing them to run more efficiently or at lower temperatures? How do the nature of the single-atom catalyst and the surface it sits on affect its binding with carbon monoxide and the way the reaction proceeds?

    The team plans to return to SSRL in January to continue the work.

    See the full article here .


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    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.

     
  • richardmitnick 9:05 am on August 23, 2018 Permalink | Reply
    Tags: , , , Bouncing barrier, , Electron Microscopy, , , NASA Researchers Find Evidence of Planet-Building Clumps, Planetesimal formation   

    From NASA Ames: “NASA Researchers Find Evidence of Planet-Building Clumps” 

    NASA Ames Icon

    From NASA AMES

    Aug. 21, 2018
    Darryl Waller
    NASA Ames Research Center, Silicon Valley
    650-604-2675
    darryl.e.waller@nasa.gov

    Noah Michelsohn
    NASA Johnson Space Center, Houston
    281-483-5111
    noah.j.michelsohn@nasa.gov

    1
    False-color image of Allendale meteorite showing the apparent golf ball size clumps. Credits: NASA/J. Simon and J. Cuzzi

    NASA scientists have found the first evidence supporting a theory that golf ball-size clumps of space dust formed the building blocks of our terrestrial planets.

    A new paper from planetary scientists at the Astromaterials Research and Exploration Science Division (ARES) at NASA’s Johnson Space Center in Houston, Texas, and NASA’s Ames Research Center in Silicon Valley, California, provides evidence for an astrophysical theory called “pebble accretion” where golf ball-sized clumps of space dust came together to form tiny planets, called planetesimals, during the early stages of planetary formation.

    “This is very exciting because our research provides the first direct evidence supporting this theory,” said Justin Simon, a planetary researcher in ARES. “There have been a lot of theories about planetesimal formation, but many have been stymied by a factor called the ‘bouncing barrier.’”

    “The bouncing barrier principle stipulates that planets cannot form directly through the accumulation of small dust particles colliding in space because the impact would knock off previously attached aggregates, stalling growth. Astrophysicists had hypothesized that once the clumps grew to the size of a golf ball, any small particle colliding with the clump would knock other material off. Yet, if the colliding objects were not the size of a particle, but much larger – for example, clumps of dust the size of a golf ball – that they could exhibit enough gravity to hold themselves together in clusters to form larger bodies.”

    2
    Mosaic photograph of the ancient Northwest Africa 5717 ordinary chondrite with clusters of particles. Credits: NASA/J. Simon and J. Cuzzi

    The research provides evidence of a common, possibly universal, dust sticking process from studying two ancient meteorites – Allende and Northwest Africa 5717 – that formed in the pre-planetary period of the Solar System and have remained largely unaltered since that time. Scientists know through dating methods that these meteorites are older than Earth, Moon, and Mars, which means they have remained unaltered since the birth of the Solar System. The meteorites studied for this research are so old that they are often used to date the Solar System itself.

    The meteorites were analyzed using electron microscope images and high-resolution photomicrographs that showed particles within the meteorite slices appeared to concentrate together in three to four-centimeter clumps. The existence of the clumps demonstrates that the meteorites themselves were produced by the clustering of golf ball-sized objects, providing strong evidence that the process was possible for other bodies as well.

    The research, titled “Particle size distributions in chondritic meteorites: Evidence for pre-planetesimal histories,” was published in the journal Earth and Planetary Science Letters in July. The publication culminated six years of research that was led by planetary scientists Simon at Johnson and Jeffrey Cuzzi at Ames.

    Dig up more about how NASA studies meteorites, visit:

    https://ares.jsc.nasa.gov/

    See the full article here .

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    Ames Research Center, one of 10 NASA field Centers, is located in the heart of California’s Silicon Valley. For over 60 years, Ames has led NASA in conducting world-class research and development. With 2500 employees and an annual budget of $900 million, Ames provides NASA with advancements in:
    Entry systems: Safely delivering spacecraft to Earth & other celestial bodies
    Supercomputing: Enabling NASA’s advanced modeling and simulation
    NextGen air transportation: Transforming the way we fly
    Airborne science: Examining our own world & beyond from the sky
    Low-cost missions: Enabling high value science to low Earth orbit & the moon
    Biology & astrobiology: Understanding life on Earth — and in space
    Exoplanets: Finding worlds beyond our own
    Autonomy & robotics: Complementing humans in space
    Lunar science: Rediscovering our moon
    Human factors: Advancing human-technology interaction for NASA missions
    Wind tunnels: Testing on the ground before you take to the sky

    NASA image

     
  • richardmitnick 12:41 pm on January 20, 2018 Permalink | Reply
    Tags: , , , , , Electron Microscopy, Meteoritic stardust unlocks timing of supernova dust formation,   

    From Carnegie Institution for Science: “Meteoritic stardust unlocks timing of supernova dust formation” 

    Carnegie Institution for Science
    Carnegie Institution for Science

    January 18, 2018
    Conel Alexander
    Larry Nittler

    Dust is everywhere—not just in your attic or under your bed, but also in outer space. To astronomers, dust can be a nuisance by blocking the light of distant stars, or it can be a tool to study the history of our universe, galaxy, and Solar System.

    For example, astronomers have been trying to explain why some recently discovered distant, but young, galaxies contain massive amounts of dust. These observations indicate that type II supernovae—explosions of stars more than ten times as massive as the Sun—produce copious amounts of dust, but how and when they do so is not well understood.

    1
    An electron microscope image of a micron-sized supernova silicon carbide, SiC, stardust grain (lower right) extracted from a primitive meteorite. Such grains originated more than 4.6 billion years ago in the ashes of Type II supernovae, typified here by a Hubble Space Telescope image of the Crab Nebula, the remnant of a supernova explosion in 1054. Laboratory analysis of such tiny dust grains provides unique information on these massive stellar explosions. (1 μm is one millionth of a meter.) Image credits: NASA and Larry Nittler.

    New work from a team of Carnegie cosmochemists published by Science Advances reports analyses of carbon-rich dust grains extracted from meteorites that show that these grains formed in the outflows from one or more type II supernovae more than two years after the progenitor stars exploded. This dust was then blown into space to be eventually incorporated into new stellar systems, including in this case, our own.

    The researchers—led by former-postdoctoral fellow Nan Liu, along with Larry Nittler, Conel Alexander, and Jianhua Wang of Carnegie’s Department of Terrestrial Magnetism—came to their conclusion not by studying supernovae with telescopes. Rather, they analyzed microscopic silicon carbide, SiC, dust grains that formed in supernovae more than 4.6 billion years ago and were trapped in meteorites as our Solar System formed from the ashes of the galaxy’s previous generations of stars.

    Some meteorites have been known for decades to contain a record of the original building blocks of the Solar System, including stardust grains that formed in prior generations of stars.

    “Because these presolar grains are literally stardust that can be studied in detail in the laboratory,” explained Nittler, “they are excellent probes of a range of astrophysical processes.”

    For this study, the team set out to investigate the timing of supernova dust formation by measuring isotopes—versions of elements with the same number of protons but different numbers of neutrons—in rare presolar silicon carbide grains with compositions indicating that they formed in type II supernovae.

    Certain isotopes enable scientists to establish a time frame for cosmic events because they are radioactive. In these instances, the number of neutrons present in the isotope make it unstable. To gain stability, it releases energetic particles in a way that alters the number of protons and neutrons, transmuting it into a different element.

    The Carnegie team focused on a rare isotope of titanium, titanium-49, because this isotope is the product of radioactive decay of vanadium-49 which is produced during supernova explosions and transmutes into titanium-49 with a half-life of 330 days. How much titanium-49 gets incorporated into a supernova dust grain thus depends on when the grain forms after the explosion.

    Using a state-of-the-art mass spectrometer to measure the titanium isotopes in supernova SiC grains with much better precision than could be accomplished by previous studies, the team found that the grains must have formed at least two years after their massive parent stars exploded.

    Because presolar supernova graphite grains are isotopically similar in many ways to the SiC grains, the team also argues that the delayed formation timing applies generally to carbon-rich supernova dust, in line with some recent theoretical calculations.

    “This dust-formation process can occur continuously for years, with the dust slowly building up over time, which aligns with astronomer’s observations of varying amounts of dust surrounding the sites of stellar explosions,” added lead author Liu. “As we learn more about the sources for dust, we can gain additional knowledge about the history of the universe and how various stellar objects within it evolve.”

    See the full article here .

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    Carnegie Institution of Washington Bldg

    Andrew Carnegie established a unique organization dedicated to scientific discovery “to encourage, in the broadest and most liberal manner, investigation, research, and discovery and the application of knowledge to the improvement of mankind…” The philosophy was and is to devote the institution’s resources to “exceptional” individuals so that they can explore the most intriguing scientific questions in an atmosphere of complete freedom. Carnegie and his trustees realized that flexibility and freedom were essential to the institution’s success and that tradition is the foundation of the institution today as it supports research in the Earth, space, and life sciences.

    6.5 meter Magellan Telescopes located at Carnegie’s Las Campanas Observatory, Chile.
    6.5 meter Magellan Telescopes located at Carnegie’s Las Campanas Observatory, Chile

     
  • richardmitnick 10:53 am on January 4, 2018 Permalink | Reply
    Tags: , , Electron Microscopy, MicroED=micro-electron diffraction, ,   

    From UCLA Newsroom: “Imaging technique could be ‘new ballgame’ in drug development” 


    UCLA Newsroom

    January 02, 2018
    Tami Dennis

    UCLA researcher Tamir Gonen explores the potential of MicroED in neurological diseases.

    1
    Courtesy of Tamir Gonen
    Tamir Gonen published his proof of principle paper [eLIFE] on MicroED in 2013.

    Biochemistry and structural biology are surprisingly — at least to the uninitiated — visual fields. This is especially true in the study of proteins. Scientists like to see the structure of proteins within cells to help them truly understand how they work, how they don’t work or how they can be modified to work as they should. That is, how they can be targeted with drugs to cure disease.

    Current methods, however, have their downsides. Many widely used techniques require large amounts of protein for analysis, even though many diseases are caused by proteins that are far from abundant or that are difficult to amass in large quantities. A new method pioneered by a professor who recently joined UCLA overcomes this challenge, offering untold potential in the exploration of disease and treatment.

    Called “MicroED,” for micro-electron diffraction, the technique uses high-powered electron microscopy to determine the structure of proteins with atomic precision, using samples that are only one-billionth the size required by other imaging methods.

    Tamir Gonen, a new professor of physiology and biological chemistry at the David Geffen School of Medicine at UCLA, is the developer of MicroED. For the past five years, Gonen has been spearheading the exploration of MicroED in his lab at the Janelia Research Campus of the Howard Hughes Medical Institute near Washington D.C.

    Now, in joining UCLA’s faculty, Gonen’s goal is to set up a lab centered on this new imaging tool. Already the university is using the technique in the labs of Jose Rodriguez, assistant professor of biochemistry, and David Eisenberg, a professor of chemistry and biochemistry and of biological chemistry. Both use MicroED to view the structures of proteins involved in neurodegeneration.

    “With MicroED, the way we think about disease is going to be different,” Gonen said. “Because it uses minute samples and the resolution we get is very high, problems that were beyond our reach are suddenly attainable. We can see individual atoms and even peer deeper into subatomic space and see things that have not been seen before.”

    2
    Samples used in MicroED resemble jewels with one exception, they are made out of biological material rather than precious mineral. Gonen lab.

    Gonen began working on the technique at the Howard Hughes Medical Institute Janelia Research Campus, where he was a group leader. Upon moving to UCLA Gonen is now an investigator of the Howard Hughes Medical Institute and professor of physiology and biological chemistry. Prior to that, he was an assistant professor, then a tenured associate professor, at the University of Washington School of Medicine, as well as a Howard Hughes Medical Institute Early Career Scientist.

    Since 2013, which marked his publication of a proof of principle paper on MicroED [eLIFE], Gonen has been an advocate for the technique. As other researchers have come to understand the long-sought imaging potential MicroED offers, about 20 institutions worldwide have begun setting up MicroED labs, many with Gonen’s help.

    “I have fantastic folks working in my lab, and they are extremely collegial and want to help others get their science done,” Gonen said.

    That focus on getting “science done” — and MicroED itself — has enormous ramifications for the treatment of HIV, Parkinson’s, Alzheimer’s and other neurodegenerative diseases. “When you’re talking about drug discovery, it’s a whole new ballgame,” Gonen said.

    Gonen’s development of MicroED stemmed from his study of cell membranes, specifically the protein gateways within those membranes.

    These gateways can help cells maintain healthy homeostasis in which everything works as it should — think of it as a biological “peace.” When things go wrong, however, as happens with disease, these gateways might allow too much of one substance, such as water or sugar, in or out.

    3
    This illustration of a protein shows an example of a structure that could only be determined by the capabilities of micro-electron diffraction. Gonen lab.

    Gonen knew that targeting these gateways — or targeting their function — could lead to innovative ways to control disease and help patients. But he and other scientists needed good images to facilitate the design of better drugs.

    “More than 90 percent of all medicines sold these days target G-protein coupled receptors,” Gonen said. “When you feel pain, when you see light, when you taste, when you have any neurological sensation, all of this is occurring because of these receptors.”

    Another potential, and timely, target of this type: opioid receptors. “Opioids are an increasingly challenging problem, and not surprisingly there exists an opioid receptor,” Gonen said.

    MicroED makes it possible to image these G-protein coupled receptors, which move around a lot. This movement has made it difficult for traditional methods to capture images of them.

    MicroED’s potential goes far beyond such receptors, however.

    Larry Zipursky, a distinguished professor biological chemistry and the leader of the neuroscience research theme at the David Geffen School of Medicine at UCLA, called the approach “revolutionary.”

    “This technique uses a rational approach to disease,” Zipursky said. “It allows researchers to assess the structure of abnormal proteins that give rise to disease; from this structural determination, they can assess the disease in a more strategic way.”

    Gonen is enthusiastic about the larger potential as well. “For a medical school, this is going to be quite a resource for pushing research forward. I’m hoping to collaborate with a lot of people.”

    In fact, he’s already working on several projects, including one that points to a way to make more efficient HIV medicines. This is in addition to the projects with Eisenberg and Rodriguez, who’s studying the conversion of proteins from a normal state into an abnormal, clumped — or aggregated — state, as seen in Alzheimer’s and other diseases of the brain and nervous system.

    “We need new and better treatments for neurodegenerative diseases, one way to achieve this is to understand how atomic scale changes in the brain lead to disease. What do the structures look like before and after, and, quite simply, how are they so toxic?” Rodriguez said. “MicroED may finally open the door to that understanding.”

    The potential of such collaborations is what brought Gonen — and his emphasis on MicroED — to UCLA.

    “What I like about UCLA is it’s a top-rate institution — you can find some expert in every field,” Gonen said. “They’re a world leader, but they come without the ego you may find at other institutions.”

    That collaboration, he’s convinced, will lead to new approaches, new discoveries and new cures.

    Further papers:
    >Structure of catalase determined by MicroED
    Taking the measure of MicroED
    Protein structure determination by MicroED

    See the full article here .

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    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

     
  • richardmitnick 1:34 pm on December 21, 2017 Permalink | Reply
    Tags: , , Electron Microscopy, Magnetic fields of bacterial cells and magnetic nano-objects in liquid can be studied at high resolution using electron microscopy,   

    From Ames National Lab: “Ames Laboratory-led research team maps magnetic fields of bacterial cells and nano-objects for the first time” 

    Ames Laboratory

    Dec. 21, 2017
    Contacts:
    Tanya Prozorov, Division of Materials Sciences and Engineering
    tprozor@ameslab.gov
    (515) 294-3376

    Laura Millsaps, Ames Laboratory Public Affairs
    millsaps@ameslab.gov
    (515) 294-3474

    A research team led by a scientist from the U.S. Department of Energy’s Ames Laboratory has demonstrated for the first time that the magnetic fields of bacterial cells and magnetic nano-objects in liquid can be studied at high resolution using electron microscopy. This proof-of-principle capability allows first-hand observation of liquid environment phenomena, and has the potential to vastly increase knowledge in a number of scientific fields, including many areas of physics, nanotechnology, biofuels conversion, biomedical engineering, catalysis, batteries and pharmacology.

    1
    Left: Schematic of the off-axis electron holography using a fluid cell. Right: (A)
    Hologram of a magnetite nanocrystal chain released from a magnetotactic
    bacterium, and (B) corresponding magnetic induction map.

    “It is much like being able to travel to a Jurassic Park and witness dinosaurs walking around, instead of trying to guess how they walked by examining a fossilized skeleton,” said Tanya Prozorov, an associate scientist in Ames Laboratory’s Division of Materials Sciences and Engineering.

    Prozorov works with biological and bioinspired magnetic nanomaterials, and faced what initially seemed to be an insurmountable challenge of observing them in their native liquid environment. She studies a model system, magnetotactic bacteria, which form perfect nanocrystals of magnetite. In order to best learn how bacteria do this, she needed an alternative to the typical electron microscopy process of handling solid samples in vacuum, where soft matter is studied in prepared, dried, or vitrified form.

    For this work, Prozorov received DOE recognition through an Office of Science Early Career Research Program grant to use cutting-edge electron microscopy techniques with a liquid cell insert to learn how the individual magnetic nanocrystals form and grow with the help of biological molecules, which is critical for making artificial magnetic nanomaterials with useful properties.

    To study magnetism in bacteria, she applied off-axis electron holography, a specialized technique that is used for the characterization of magnetic nanostructures in the transmission electron microscope, in combination with the liquid cell.

    “When we look at samples prepared in the conventional way, we have to make many assumptions about their properties based on their final state, but with the new technique, we can now observe these processes first-hand,” said Prozorov. “It can help us understand the dynamics of macromolecule aggregation, nanoparticle self-assembly, and the effects of electric and magnetic fields on that process.”

    “This method allows us to obtain large amounts of new information,” said Prozorov. “It is a first step, proving that the mapping of magnetic fields in liquid at the nanometer scale with electron microscopy could be done; I am eager to see the discoveries it could foster in other areas of science.”

    The work was done in collaboration with the Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons and Peter Grünberg Institute, Forschungszentrum Jülich, Germany.

    The research is detailed in the paper, Off-axis electron holography of bacterial cells and magnetic nanoparticles in liquid, by T. Prozorov, T.P. Almeida, A. Kovács, and R.E. Dunin-Borkowski: and published in the Journal of the Royal Society Interface.

    See the full article here .

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    Ames Laboratory is a government-owned, contractor-operated research facility of the U.S. Department of Energy that is run by Iowa State University.

    For more than 60 years, the Ames Laboratory has sought solutions to energy-related problems through the exploration of chemical, engineering, materials, mathematical and physical sciences. Established in the 1940s with the successful development of the most efficient process to produce high-quality uranium metal for atomic energy, the Lab now pursues a broad range of scientific priorities.

    Ames Laboratory is a U.S. Department of Energy Office of Science national laboratory operated by Iowa State University. Ames Laboratory creates innovative materials, technologies and energy solutions. We use our expertise, unique capabilities and interdisciplinary collaborations to solve global problems.

    Ames Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.
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  • richardmitnick 6:02 pm on November 21, 2017 Permalink | Reply
    Tags: , , , , Electron Microscopy, , , , Plasma-facing material   

    From BNL: “Designing New Metal Alloys Using Engineered Nanostructures” 

    Brookhaven Lab

    Stony Brook University assistant professor Jason Trelewicz brings his research to design and stabilize nanostructures in metals to Brookhaven Lab’s Center for Functional Nanomaterials.

    1
    Materials scientist Jason Trelewicz in an electron microscopy laboratory at Brookhaven’s Center for Functional Nanomaterials, where he characterizes nanoscale structures in metals mixed with other elements.

    Materials science is a field that Jason Trelewicz has been interested in since he was a young child, when his father—an engineer—would bring him to work. In the materials lab at his father’s workplace, Trelewicz would use optical microscopes to zoom in on material surfaces, intrigued by all the distinct features he would see as light interacted with different samples.

    Now, Trelewicz—an assistant professor in the College of Engineering and Applied Sciences’ Department of Materials Science and Chemical Engineering with a joint appointment in the Institute for Advanced Computational Science at Stony Brook University and principal investigator of the Engineered Metallic Nanostructures Laboratory—takes advantage of the much higher magnifications of electron microscopes to see tiny nanostructures in fine detail and learn what happens when they are exposed to heat, radiation, and mechanical forces. In particular, Trelewicz is interested in nanostructured metal alloys (metals mixed with other elements) that incorporate nanometer-sized features into classical materials to enhance their performance. The information collected from electron microscopy studies helps him understand interactions between structural and chemical features at the nanoscale. This understanding can then be employed to tune the properties of materials for use in everything from aerospace and automotive components to consumer electronics and nuclear reactors.

    Since 2012, when he arrived at Stony Brook University, Trelewicz has been using the electron microscopes and the high-performance computing (HPC) cluster at the Center for Functional Nanomaterials (CFN)—a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory—to perform his research.

    “At the time, I was looking for ways to apply my idea of stabilizing nanostructures in metals to an application-oriented problem,” said Trelewicz. “I’ve long been interested in nuclear energy technologies, initially reading about fusion in grade school. The idea of recreating the processes responsible for the energy we receive from the sun here on earth was captivating, and fueled my interest in nuclear energy throughout my entire academic career. Though we are still very far away from a fusion reactor that generates power, a large international team on a project under construction in France called ITER is working to demonstrate a prolonged fusion reaction at a large scale.”

    Plasma-facing materials for fusion reactors

    Nuclear fusion—the reaction in which atomic nuclei collide—could provide a nearly unlimited supply of safe, clean energy, like that naturally produced by the sun through fusing hydrogen nuclei into helium atoms. Harnessing this carbon-free energy in reactors requires generating and sustaining a plasma, an ionized gas, at the very high temperatures at which fusion occurs (about six times hotter than the sun’s core) while confining it using magnetic fields. Of the many challenges currently facing fusion reactor demonstrations, one of particular interest to Trelewicz is creating viable materials to build a reactor.

    2
    A model of the ITER tokamak, an experimental machine designed to harness the energy of fusion. A powerful magnetic field is used to confine the plasma, which is held in a doughnut-shaped vessel. Credit: ITER Organization.

    “The formidable materials challenges for fusion are where I saw an opportunity for my research—developing materials that can survive inside the fusion reactor, where the plasma will generate high heat fluxes, high thermal stresses, and high particle and neutron fluxes,” said Trelewicz. “The operational conditions in this environment are among the harshest in which one could expect a material to function.”

    A primary candidate for such “plasma-facing material” is tungsten, because of its high melting point—the highest one among metals in pure form—and low sputtering yield (number of atoms ejected by energetic ions from the plasma). However, tungsten’s stability against recrystallization, oxidation resistance, long-term radiation tolerance, and mechanical performance are problematic.

    Trelewicz thinks that designing tungsten alloys with precisely tailored nanostructures could be a way to overcome these problems. In August, he received a $750,000 five-year award from the DOE’s Early Career Research Program to develop stable nanocrystalline tungsten alloys that can withstand the demanding environment of a fusion reactor. His research is combining simulations that model atomic interactions and experiments involving real-time ion irradiation exposure and mechanical testing to understand the fundamental mechanisms responsible for the alloys’ thermal stability, radiation tolerance and mechanical performance. The insights from this research will inform the design of more resilient alloys for fusion applications.

    In addition to the computational resources they use at their home institution, Trelewicz and his lab group are using the HPC cluster at the CFN—and those at other DOE facilities, such as Titan at Oak Ridge Leadership Computing Facility (a DOE Office of Science User Facility at Oak Ridge National Laboratory)—to conduct large-scale atomistic simulations as part of the project.

    ORNL Cray Titan XK7 Supercomputer

    “The length scales of the structures we want to design into our materials are on the order of a few nanometers to 100 nanometers, and a single simulation can involve up to 10 million atoms,” said Trelewicz. “Using HPC clusters, we can build a system atom-by-atom, representative of the structure we would like to explore experimentally, and run simulations to study the response of that system under various external stimuli. For example, we can fire a high-energy atom into the system and watch what happens to the material and how it evolves, hundreds or thousands of times. Once damage has accumulated in the structure, we can simulate thermal and mechanical forces to understand how defect structure impacts other behavior.”

    These simulations inform the structures and chemistries of experimental alloys, which Trelewicz and his students fabricate at Stony Brook University through high-energy milling. To characterize the nanoscale structure and chemical distribution of the engineered alloys, they extensively use the microscopy facilities at the CFN—including scanning electron microscopes, transmission electron microscopes, and scanning transmission electron microscopes. Imaging is conducted at high resolution and often combined with heating within the microscope to examine in real time how the structures evolve with temperature. Experiments are also conducted at other DOE national labs, such as Sandia through collaboration with materials scientist Khalid Hattar of the Ion Beam Laboratory. Here, students in Trelewicz’s research group simultaneously irradiate the engineered alloys with an ion beam and image them with an electron microscope over the course of many days.

    3
    Trelewicz and his students irradiated a nanostructured tungsten-titanium alloy with high-energy gold ions to explore the radiation tolerance of this novel material.

    “Though this damage does not compare to what the material would experience in a reactor, it provides a starting point to evaluate whether or not the engineered material could indeed address some of the limitations of tungsten for fusion applications,” said Trelewicz.

    Electron microscopy at the CFN has played a key role in an exciting discovery that Trelewicz’s students recently made: an unexpected metastable-to-stable phase transition in thin films of nanostructured tungsten. This phase transition drives an abnormal “grain” growth process in which some crystalline nanostructure features grow very dramatically at the expense of others. When the students added chromium and titanium to tungsten, this metastable phase was completely eliminated, in turn enhancing the thermal stability of the material.

    “One of the great aspects of having both experimental and computational components to our research is that when we learn new things from our experiments, we can go back and tailor the simulations to more accurately reflect the actual materials,” said Trelewicz.

    Other projects in Trelewicz’s research group.

    The research with tungsten is only one of many projects ongoing in the Engineered Metallic Nanostructures Laboratory.

    “All of our projects fall under the umbrella of developing new metal alloys with enhanced and/or multifunctional properties,” said Trelewicz. “We are looking at different strategies to optimize material performance by collectively tailoring chemistry and microstructure in our materials. Much of the science lies in understanding the nanoscale mechanisms that govern the properties we measure at the macroscale.”

    4
    Jason Trelewicz (left) with Olivia Donaldson, who recently graduated with her PhD from Trelewicz’s group, and Jonathan Gentile, a current doctoral student, in front of the scanning electron microscope/focused-ion beam at Stony Brook University’s Advanced Energy Center. Credit: Stony Brook University.

    Through a National Science Foundation CAREER (Faculty Early Career Development Program) award, Trelewicz and his research group are exploring another class of high-strength alloys—amorphous metals, or “metallic glasses,” which are metals that have a disordered atomic structure akin to glass. Compared to everyday metals, metallic glasses are often inherently higher strength but usually very brittle, and it is difficult to make them in large parts such as bulk sheets. Trelewicz’s team is designing interfaces and engineering them into the metallic glasses—initially iron-based and later zirconium-based ones—to enhance the toughness of the materials, and exploring additive manufacturing processes to enable sheet-metal production. They will use the Nanofabrication Facility at the CFN to fabricate thin films of these interface-engineered metallic glasses for in situ analysis using electron microscopy techniques.

    In a similar project, they are seeking to understand how introducing a crystalline phase into a zirconium-based amorphous alloy to form a metallic glass matrix composite (composed of both amorphous and crystalline phases) augments the deformation process relative to that of regular metallic glasses. Metallic glasses usually fail catastrophically because strain becomes localized into shear bands. Introducing crystalline regions in the metallic glasses could inhibit the process by which strain localizes in the material. They have already demonstrated that the presence of the crystalline phase fundamentally alters the mechanism through which the shear bands form.

    Trelewicz and his group are also exploring the deformation behavior of metallic “nanolaminates” that consist of alternating crystalline and amorphous layers, and are trying to approach the theoretical limit of strength in lightweight aluminum alloys through synergistic chemical doping strategies (adding other elements to a material to change its properties).

    5
    Trelewicz and his students perform large-scale atomistic simulations to explore the segregation of solute species to grain boundaries (GBs)—interfaces between grains—in nanostructured alloys, as shown here for an aluminum-magnesium (Al-Mg) system, and its implications for the governing deformation mechanisms. They are using the insights gained through these simulations to design lightweight alloys with theoretical strengths.

    “We leverage resources of the CFN for every project ongoing in my research group,” said Trelewicz. “We extensively use the electron microscopy facilities to look at material micro- and nanostructure, very often at how interfaces are coupled with compositional inhomogeneities—information that helps us stabilize and design interfacial networks in nanostructured metal alloys. Computational modeling and simulation enabled by the HPC clusters at the CFN informs what we do in our experiments.”

    Beyond his work at CFN, Trelewicz collaborates with his departmental colleagues to characterize materials at the National Synchrotron Light Source II—another DOE Office of Science User Facility at Brookhaven.

    BNL NSLS-II


    BNL NSLS II

    “There are various ways to characterize structural and chemical inhomogeneities,” said Trelewicz. “We look at small amounts of material through the electron microscopes at CFN and on more of a bulk level at NSLS-II through techniques such as x-ray diffraction and the micro/nano probe. We combine this local and global information to thoroughly characterize a material and use this information to optimize its properties.”

    Future of next-generation materials

    When he is not doing research, Trelewicz is typically busy with student outreach. He connects with the technology departments at various schools, providing them with materials engineering design projects. The students not only participate in the engineering aspects of materials design but are also trained on how to use 3D printers and other tools that are critical in today’s society to manufacture products more cost effectively and with better performance.

    Going forward, Trelewicz would like to expand his collaborations at the CFN and help establish his research in metallic nanostructures as a core area supported by CFN and, ultimately, DOE, to achieve unprecedented properties in classical materials.

    “Being able to learn something new every day, using that knowledge to have an impact on society, and seeing my students fill gaps in our current understanding are what make my career as a professor so rewarding,” said Trelewicz. “With the resources of Stony Brook University, nearby CFN, and other DOE labs, I have an amazing platform to make contributions to the field of materials science and metallurgy.”

    Trelewicz holds a bachelor’s degree in engineering science from Stony Brook University and a doctorate in materials science and engineering with a concentration in technology innovation from MIT. Before returning to academia in 2012, Trelewicz spent four years in industry managing technology development and transition of harsh-environment sensors produced by additive manufacturing processes. He is the recipient of a 2017 Department of Energy Early Career Research Award, 2016 National Science Foundation CAREER award, and 2015 Young Leaders Professional Development Award from The Minerals, Metals & Materials Society (TMS), and is an active member of several professional organizations, including TMS, the Materials Research Society, and ASM International (the Materials Information Society).

    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.
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  • richardmitnick 11:53 am on July 29, 2017 Permalink | Reply
    Tags: 3D structure of human chromatin, , ChromEMT, , Electron Microscopy, , , ,   

    From Salk: “Salk scientists solve longstanding biological mystery of DNA organization” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    July 27, 2017

    Stretched out, the DNA from all the cells in our body would reach Pluto. So how does each tiny cell pack a two-meter length of DNA into its nucleus, which is just one-thousandth of a millimeter across?

    The answer to this daunting biological riddle is central to understanding how the three-dimensional organization of DNA in the nucleus influences our biology, from how our genome orchestrates our cellular activity to how genes are passed from parents to children.

    Now, scientists at the Salk Institute and the University of California, San Diego, have for the first time provided an unprecedented view of the 3D structure of human chromatin—the combination of DNA and proteins—in the nucleus of living human cells.

    In the tour de force study, described in Science on July 27, 2017, the Salk researchers identified a novel DNA dye that, when paired with advanced microscopy in a combined technology called ChromEMT, allows highly detailed visualization of chromatin structure in cells in the resting and mitotic (dividing) stages. By revealing nuclear chromatin structure in living cells, the work may help rewrite the textbook model of DNA organization and even change how we approach treatments for disease.

    “One of the most intractable challenges in biology is to discover the higher-order structure of DNA in the nucleus and how is this linked to its functions in the genome,” says Salk Associate Professor Clodagh O’Shea, a Howard Hughes Medical Institute Faculty Scholar and senior author of the paper. “It is of eminent importance, for this is the biologically relevant structure of DNA that determines both gene function and activity.”

    2
    A new technique enables 3D visualization of chromatin (DNA plus associated proteins) structure and organization within a cell nucleus (purple, bottom left) by painting the chromatin with a metal cast and imaging it with electron microscopy (EM). The middle block shows the captured EM image data, the front block illustrates the chromatin organization from the EM data, and the rear block shows the contour lines of chromatin density from sparse (cyan and green) to dense (orange and red). Credit: Salk Institute.

    Ever since Francis Crick and James Watson determined the primary structure of DNA to be a double helix, scientists have wondered how DNA is further organized to allow its entire length to pack into the nucleus such that the cell’s copying machinery can access it at different points in the cell’s cycle of activity. X-rays and microscopy showed that the primary level of chromatin organization involves 147 bases of DNA spooling around proteins to form particles approximately 11 nanometers (nm) in diameter called nucleosomes. These nucleosome “beads on a string” are then thought to fold into discrete fibers of increasing diameter (30, 120, 320 nm etc.), until they form chromosomes. The problem is, no one has seen chromatin in these discrete intermediate sizes in cells that have not been broken apart and had their DNA harshly processed, so the textbook model of chromatin’s hierarchical higher-order organization in intact cells has remained unverified.

    To overcome the problem of visualizing chromatin in an intact nucleus, O’Shea’s team screened a number of candidate dyes, eventually finding one that could be precisely manipulated with light to undergo a complex series of chemical reactions that would essentially “paint” the surface of DNA with a metal so that its local structure and 3D polymer organization could be imaged in a living cell. The team partnered with UC San Diego professor and microscopy expert Mark Ellisman, one of the paper’s coauthors, to exploit an advanced form of electron microscopy that tilts samples in an electron beam enabling their 3D structure to be reconstructed. By combining their chromatin dye with electron-microscope tomography, they created ChromEMT.

    The team used ChromEMT to image and measure chromatin in resting human cells and during cell division when DNA is compacted into its most dense form—the 23 pairs of mitotic chromosomes that are the iconic image of the human genome. Surprisingly, they did not see any of the higher-order structures of the textbook model anywhere.

    3
    From left: Horng Ou and Clodagh O’Shea. Credit: Salk Institute.

    “The textbook model is a cartoon illustration for a reason,” says Horng Ou, a Salk research associate and the paper’s first author. “Chromatin that has been extracted from the nucleus and subjected to processing in vitro—in test tubes—may not look like chromatin in an intact cell, so it is tremendously important to be able to see it in vivo.”

    What O’Shea’s team saw, in both resting and dividing cells, was chromatin whose “beads on a string” did not form any higher-order structure like the theorized 30 or 120 or 320 nanometers. Instead, it formed a semi-flexible chain, which they painstakingly measured as varying continuously along its length between just 5 and 24 nanometers, bending and flexing to achieve different levels of compaction. This suggests that it is chromatin’s packing density, and not some higher-order structure, that determines which areas of the genome are active and which are suppressed.

    With their 3D microscopy reconstructions, the team was able to move through a 250 nm x 1000 nm x 1000 nm volume of chromatin’s twists and turns, and envision how a large molecule like RNA polymerase, which transcribes (copies) DNA, might be directed by chromatin’s variable packing density, like a video game aircraft flying through a series of canyons, to a particular spot in the genome. Besides potentially upending the textbook model of DNA organization, the team’s results suggest that controlling access to chromatin could be a useful approach to preventing, diagnosing and treating diseases such as cancer.

    “We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus,” adds O’Shea. “It’s the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes.”

    Future work will examine whether chromatin’s structure is universal among cell types or even among organisms.

    Other authors included Sébastien Phan, Thomas Deerinck and Andrea Thor of the UC San Diego.

    The work was largely funded by the W. M. Keck Foundation, the NIH 4D Nucleome Roadmap Initiative and the Howard Hughes Medical Institute, with additional support from the William Scandling Trust, the Price Family Foundation and the Leona M. and Harry B. Helmsley Charitable Trust.

    See the full article here .

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    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 9:28 am on July 24, 2017 Permalink | Reply
    Tags: , , Electron Microscopy, , Native mass spectrometry, Signaling islands in cells: targets for precision drug design,   

    From U Washington: “Signaling islands in cells: targets for precision drug design” 

    U Washington

    University of Washington

    07.13.2017
    Leila Gray

    1
    A critical component of the cell signaling system, anchored protein kinase A, has some flexible molecular parts, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets. John Scott Lab.

    Research results reported in the journal Science overturn long-held views on a basic messaging system within living cells.

    The findings suggest new approaches to designing precisely targeted drugs for cancer and other serious diseases.

    Dr. John D. Scott, professor and chair of pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute Investigator, along with Dr. F. Donelson Smith of the UW and HHMI, led this study, which also involved Drs. Claire and Patrick Eyers and their group at the University of Liverpool. Visit the Scott lab web site, Cell Signaling in Space and Time.

    The researchers explained that key cellular communication machinery is more regionally constrained inside the cell than was previously thought. Communication via this vital system is akin to social networking on your Snapchat account.

    Within a cell, the precise positioning of such messaging components allows hormones, the body’s chief chemical communicators, to transmit information to exact places inside the cell. Accurate and very local activation of the enzyme that Scott and his group study helps assure a correct response occurs in the right place and at the right time.

    “The inside of a cell is like a crowded city,” said Scott, “It is a place of construction and tearing down, goods being transported and trash being recycled, countless messages, (such as the ones we have discovered), assembly lines flowing, and packages moving. Strategically switching on signaling enzyme islands allows these biochemical activities to keep the cell alive and is important to protect against the onset of chronic diseases such as diabetes, heart disease and certain cancers.”

    Advances in electron microscopy and native mass spectrometry enabled the researchers to determine that a critical component of the signaling system, anchored protein kinase A, remains intact during activation. Parts of the molecule are flexible, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets.

    Still, where the molecule performs its act, space is tight. The distance is, in fact, about the width of two proteins inside the cell.

    2
    Green, circled area show where the enzyme in the signalling study is active in mitochondria, the powerhouses of living cells. John D. Scott.

    “We realize that in designing drugs to reach such targets that they will have to work within very narrow confines, ” Scott said.

    One of his group’s collective goals is figuring out how to deliver precision drugs to the right address within this teeming cytoplasmic metropolis.

    “Insulating the signal so that the drug effect can’t happen elsewhere in the cell is an equally important aspect of drug development because it could greatly reduce side effects,” Scott said.

    An effort to take this idea of precision medicine a step further is part of the Institute for Targeted Therapeutics at UW Medicine in Seattle. The institute is being set up by Scott and his colleagues in the UW Department of Pharmacology.

    The scientists are collaborating with cancer researchers to better understand the molecular causes — and possible future treatments — for a certain liver malignancy. This particular liver cancer arises from a mutation that produces an abnormal form of the enzyme that is the topic of this current work, protein kinase A, and alters the enzyme’s role in cell signaling.

    Other advances that gave the researchers a clearer view of the signaling mechanisms reported in Science include CRISPR gene editing, live-cell imaging techniques, and more powerful ways to look at all components of a protein complex.

    See the full article here .

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 2:52 pm on April 3, 2017 Permalink | Reply
    Tags: , , Electron Microscopy   

    From Cornell: “New electron microscope sees more than an image” 

    Cornell Bloc

    Cornell University

    March 30, 2017
    Bill Steele
    ws21@cornell.edu

    1
    Sol Gruner, left, professor of physics, and David Muller, professor of applied and engineering physics. Chris Kitchen/University Photography

    . Their electron microscope pixel array detector (EMPAD) yields not just an image, but a wealth of information about the electrons that create the image and, from that, more about the structure of the sample.

    “We can extract local strains, tilts, rotations, polarity and even electric and magnetic fields,” explained David Muller, professor of applied and engineering physics, who developed the new device with Sol Gruner, professor of physics, and members of their research groups.

    Cornell’s Center for Technology Licensing (CTL) has licensed the invention to FEI, a leading manufacturer of electron microscopes (a division of Thermo Fisher Scientific, which supplies products and services for the life sciences through several brands). FEI expects to complete the commercialization of the design and offer the detector for new and retrofitted electron microscopes this year.

    “It’s mind-boggling to contemplate what researchers around the world will discover through this match of Cornell’s deep expertise in detector science with market leader Thermo Fisher Scientific,” said Patrick Govang, technology licensing officer at CTL.

    The scientists described their work in the February 2016 issue of the journal Microscopy and Microanalysis.

    In the usual scanning transmission electron microscope (STEM), a narrow beam of electrons is fired down through a sample, scanning back and forth to produce an image. A detector underneath reads the varying intensity of electrons coming through and sends a signal that draws an image on a computer screen.

    The EMPAD that replaces the usual detector is made up of a 128×128 array of electron-sensitive pixels, each 150 microns (millionths of a meter) square, bonded to an integrated circuit that reads out the signals – somewhat like the array of light-sensitive pixels in the sensor in a digital camera, but not to form an image. Its purpose is to detect the angles at which electrons emerge, as each electron hits a different pixel. The EMPAD is a spinoff of X-ray detectors the physicists have built for X-ray crystallography work at the Cornell High Energy Synchrotron Source (CHESS), and it can work in a similar way to reveal the atomic structure of a sample.

    Combined with the focused beam of the electron microscope, the detector allows researchers to build up a “four-dimensional” map of both position and momentum of the electrons as they pass through a sample to reveal the atomic structure and forces inside. The EMPAD is unusual in its speed, sensitivity and wide range of intensities it can record – from detecting a single electron to intense beams containing hundreds of thousands or even a million electrons.

    “It would be like taking a photograph of a sunset that showed both details on the surface of the sun and the details of darkest shadows,” Muller explained.

    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.

     
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