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Rare Supernova Discovery Ushers in New Era for Cosmology

With help from a supernova-hunting pipeline based at NERSC, astronomers captured multiple images of a gravitationally lensed Type 1a supernova. This is currently the only one, but if astronomers can find more they may be able to measure Universal expansion within four percent accuracy. Luckily, Berkeley Lab researchers do have a method for finding more.

Making Batteries From Waste Glass Bottles

Researchers at the University of California, Riverside's Bourns College of Engineering have used waste glass bottles and a low-cost chemical process to create nanosilicon anodes for high-performance lithium-ion batteries. The batteries will extend the range of electric vehicles and plug-in hybrid electric vehicles, and provide more power with fewer charges to personal electronics like cell phones and laptops.

Changing the Game

High performance computing researcher Shuaiwen Leon Song asked if hardware called 3D stacked memory could do something it was never designed to do--help render 3D graphics.

A Scientific Advance for Cool Clothing: Temperature-Wise, That Is

Stanford University researchers, with the aid of the Comet supercomputer at the San Diego Supercomputer at UC San Diego, have engineered a low-cost plastic material that could become the basis for clothing that cools the wearer, reducing the need for energy-consuming air conditioning.

Adjusting Solar Panel Angles a Few Times a Year Makes Them More Efficient

With Earth Day approaching, new research from Binghamton University-State of New York could help U.S. residents save more energy, regardless of location, if they adjust the angles of solar panels four to five times a year.

A Real CAM-Do Attitude

A multi-institutional team used resources at the Oak Ridge Leadership Computing Facility to catalog how desert plants photosynthetic processes vary. The study could help scientists engineer drought-resistant crops for food and fuel.

Predictive Power

The Consortium for Advanced Simulation of Light Water Reactors carried out the largest time-dependent simulation of a nuclear reactor ever to support Tennessee Valley Authority and Westinghouse Electric Company during the startup of Watts Bar Unit 2, the first new US nuclear reactor in 20 years. The simulation was carried out primarily on OLCF resources.

Advantage: Water

When water comes in for a landing on the common catalyst titanium oxide, it splits into hydroxyls just under half the time. Water's oxygen and hydrogen atoms shift back and forth between existing as water or hydroxyls, and water has the slightest advantage, like the score in a highly competitive tennis game.

Self-Assembling Polymers Provide Thin Nanowire Template

In a recent study, a team of researchers from Argonne, the University of Chicago and MIT has developed a new way to create some of the world's thinnest wires, using a process that could enable mass manufacturing with standard types of equipment.

Did You Catch That? Robot's Speed of Light Communication Could Protect You From Danger

If you were monitoring a security camera and saw someone set down a backpack and walk away, you might pay special attention - especially if you had been alerted to watch that particular person. According to Cornell University researchers, this might be a job robots could do better than humans, by communicating at the speed of light and sharing images.


ORNL to Collaborate with Five Small Businesses to Advance Energy Tech

Five small companies have been selected to partner with the Department of Energy's Oak Ridge National Laboratory to move technologies in commercial refrigeration systems, water power generation, bioenergy and battery manufacturing closer to the marketplace.

U.S. Department of Energy's INCITE Program Seeks Advanced Computational Research Proposals for 2018

The Department of Energy's INCITE program will be accepting proposals for high-impact, computationally intensive research campaigns in a broad array of science, engineering, and computer science domains.

New Berkeley Lab Project Turns Waste Heat to Electricity

A new Berkeley Lab project seeks to efficiently capture waste heat and convert it to electricity, potentially saving California up to $385 million per year. With a $2-million grant from the California Energy Commission, Berkeley Lab scientists will work with Alphabet Energy to create a cost-effective thermoelectric waste heat recovery system.

New SLAC Theory Institute Aims to Speed Research on Exotic Materials at Light Sources

A new institute at the Department of Energy's SLAC National Accelerator Laboratory is using the power of theory to search for new types of materials that could revolutionize society - by making it possible, for instance, to transmit electricity over power lines with no loss.

Lenvio Inc. Exclusively Licenses ORNL Malware Behavior Detection Technology

Virginia-based Lenvio Inc. has exclusively licensed a cyber security technology from the Department of Energy's Oak Ridge National Laboratory that can quickly detect malicious behavior in software not previously identified as a threat.

Argonne Scientist and Nobel Laureate Alexei Abrikosov Dies at 88

Alexei Abrikosov, an acclaimed physicist at the U.S. Department of Energy's Argonne National Laboratory who received the 2003 Nobel Prize in Physics for his work on superconducting materials, died Wednesday, March 29. He was 88.

Jefferson Lab Accomplishes Critical Milestones Toward Completion of 12 GeV Upgrade

The Continuous Electron Beam Accelerator Facility (CEBAF) at the U.S. Department of Energy's Thomas Jefferson National Accelerator Facility has achieved two major commissioning milestones and is now entering the final stretch of work to conclude its first major upgrade. Recently, the CEBAF accelerator delivered electron beams into two of its experimental halls, Halls B and C, at energies not possible before the upgrade for commissioning of the experimental equipment currently in each hall. Data were recorded in each hall, which were then confirmed to be of sufficient quality to allow for particle identification, a primary indicator of good detector operation.

Valerie Taylor Named Argonne National Laboratory's Mathematics and Computer Science Division Director

Computer scientist Valerie Taylor has been appointed as the next director of the Mathematics and Computer Science division at Argonne, effective July 3, 2017.

Three SLAC Employees Awarded Lab's Highest Honor

At a March 7 ceremony, three employees of the Department of Energy's SLAC National Accelerator Laboratory were awarded the lab's highest honor ­- the SLAC Director's Award.

Dan Sinars Represents Sandia in First Energy Leadership Class

Dan Sinars, a senior manager in Sandia National Laboratories' pulsed power center, which built and operates the Z facility, is the sole representative from a nuclear weapons lab in a new Department of Energy leadership program that recently visited Sandia.


Ultrafast Imaging Reveals the Electron's New Clothes

Scientists use high-speed electrons to visualize "dress-like" distortions in the atomic lattice. This work reveals the vital role of electron-lattice interactions in manganites. This material could be used in data-storage devices with increased data density and reduced power requirements.

One Small Change Makes Solar Cells More Efficient

For years, scientists have explored using tiny drops of designer materials, called quantum dots, to make better solar cells. Adding small amounts of manganese decreases the ability of quantum dots to absorb light but increases the current produced by an average of 300%.

Electronic "Cyclones" at the Nanoscale

Through highly controlled synthesis, scientists controlled competing atomic forces to let spiral electronic structures form. These polar vortices can serve as a precursor to new phenomena in materials. The materials could be vital for ultra-low energy electronic devices.

In a Flash! A New Way for Making Ceramics

A new process controllably but instantly consolidates ceramic parts, potentially important for manufacturing.

Deciphering Material Properties at the Single-Atom Level

Scientists determine the precise location and identity of all 23,000 atoms in a nanoparticle.

Smallest Transistor Ever

It has long been thought that building nanometer-sized transistors was impossible. Simply put, the physics and atomic structural imperfections couldn't be overcome. However, scientists built fully functional, nanometer-sized transistors.

Creation of Artificial Atoms

For the first time, scientists created a tunable artificial atom in graphene. The results from this research demonstrate a viable, controllable, and reversible technique to confine electrons in graphene.

Developing Tools to Understand Lithium-Ion Battery Instabilities

Scientists develop tools to understand Li-ion battery instabilities, enabling the study of electrodes and solid-electrolyte interphase formation.

Skyrmions Created with a Special Spiral

Researchers at Argonne have found a way to control the creation of special textured surfaces, called skyrmions, in magnetically ordered materials.

Coming Together, Falling Apart, and Starting Over, Battery Style

Scientists built a new device that shows what happens when electrode, electrolyte, and active materials meet in energy storage technologies.


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X-Ray Study Reveals Long-Sought Insights Into Potential Drug Target

Article ID: 672303

Released: 2017-04-03 13:00:43

Source Newsroom: SLAC National Accelerator Laboratory

  • Credit: Greg Stewart/SLAC National Accelerator Laboratory

    Researchers use powerful X-rays to reveal molecular structures at the site where drug compounds interact with cell receptors. These structures help point the way to designing medicines of the future.

  • Credit: Greg Stewart/SLAC National Accelerator Laboratory

    Although the two angiotensin II receptors are thought to be very similar, an X-ray study showed clear differences in the pockets where the receptors bind to drug-like compounds. This illustration shows details in the pocket structures of AT2 (left) and AT1 (right).

  • Credit: Greg Stewart/SLAC National Accelerator Laboratory

    A depiction of the AT2 receptor (gray spirals and filaments) extending through a cell membrane; the blue ovals represent the membrane’s inner and outer surfaces. A potential drug compound is bound into the receptor’s exterior pocket (yellow) stabilizing the receptor in an active-like conformation. This would normally lead to activation of G-proteins and spreading a signal throughout the cell. But in the case of AT2, the place where G-proteins dock to receive the signal is blocked by a spiral-shaped helix (orange) that is part of the receptor. This new detail helps explain why AT2 receptors do not bind and activate G-proteins, but instead likely transmit the signal inside the cell via other yet unknown mechanisms.

X-ray studies done in part at the Department of Energy’s SLAC National Accelerator Laboratory have produced surprising insights into the workings of a hormone receptor associated with blood pressure regulation. Researchers believe it could be a target for new medicines related to cardiovascular conditions, neuropathic pain and tissue growth.

Using powerful X-rays from SLAC's Linac Coherent Light Source (LCLS) and Argonne National Laboratory's Advanced Photon Source (APS), scientists discovered new structural details of an angiotensin II receptor called AT2 that has puzzled researchers for two decades. It is one of two angiotensin II receptors, and its partner, AT1, has been successfully used as a target for high blood pressure medications.

The information they uncovered could give drug developers a new path for compounds that combat pain and inflammation or promote tissue regeneration by docking snugly into a pocket in AT2.

"Unlike its sibling AT1, the AT2 receptor has not been fully understood," said Vadim Cherezov, chemistry professor at the University of Southern California and principal investigator of the study published today in Nature. "Through this study we uncovered many important details about the AT2 receptor structure and how it binds to chemical compounds, information that will stimulate further studies of the receptor’s function and could enable an exciting next step in drug discovery."

Two Receptors, Many Mysteries

Both angiotensin II receptors, AT1 and AT2, are key components of a hormone system that helps regulate blood pressure and sodium levels in the blood. They are known as “membrane proteins” because they straddle the plasma membranes of cells, where they receive signals from hormones outside the cell and pass them along to soluble partners inside the cell, such as G proteins or β-arrestins, setting off a cascade of events that spread the signal cell-wide.

Many hypertension medications currently on the market target the AT1 receptor because of its well-understood role in blood pressure regulation; they block AT1 to bring blood pressure down. Cherezov led earlier experiments at LCLS that provided structural details of receptor blockers bound to AT1. The AT2 receptor, on the other hand, is still an elusive drug target despite multiple studies of its function. Some, but not all, have shown it counteracts the effects of AT1; others point to its potential for tissue protection and regeneration; and still others suggest it could play a role in blocking pain.

"There are no approved drugs yet that act on AT2 receptors, but pharmaceutical companies are actively working on developing compounds that will activate or block these receptors," Cherezov said. "One such compound, called EMA401, is being tested in patients for the treatment of neuropathic pain.”

In the latest study, Cherezov's team set out to do two things: find out how AT2 differs from AT1, so they can find ways of selectively activating or blocking it; and better understand why AT2 – which like AT1 has all the classic features of a G-protein coupled receptor (GPCR) – fails to activate G-proteins, which spread signals inside cells, or interact with arrestin, which turns those signals off.

Biology Under X-Ray Light

In the experiments, the researchers looked at two different kinds of samples, which were formed into crystals for examination with X-rays. In one, the AT2 receptor was bound to a selective compound, one that binds only to AT2. These crystals were so small that they could only be studied at SLAC's X-ray free-electron laser LCLS, where they were streamed across a beam of ultrafast X-ray pulses.

In the other, a non-selective compound was bound to both AT1 and AT2. These samples, which formed larger crystals, were probed at Argonne's APS synchrotron light source. APS and LCLS are DOE Office of Science User Facilities.

Unexpected Outcomes

The results of the experiments were surprising in several ways, according to Cherezov. First, although both compounds were designed to block and deactivate the receptors, they left AT2 in a state that appeared to be active. But on the inward-facing side of AT2, the site where a G-protein would normally bind and spread the signal was blocked. "This basically explains why these receptors do not activate G-proteins," Cherezov said. "They are activated but self-inhibited."

In addition, although AT1 and AT2 were thought to be very similar, the pockets where the receptors bind to the compounds exhibited marked differences.

"This is something we have never seen with GPCRs," Cherezov said. "The idea was always that receptors that bind to the same compounds would have very similar pockets, so efforts to develop drugs that act on AT2 started with the same basic structures as drugs that act on AT1. Now we see that we may have to start with entirely different drug-like molecules that are tailored to fit the AT2 receptor, which could set the drug discovery process in a different direction."

SLAC staff scientist Mark Hunter said, "This kind of room-temperature measurement on interesting membrane protein targets is something that LCLS is well-suited to perform. Membrane proteins remain elusive targets for high-resolution structural studies, and researchers can spend many years trying to obtain crystals that are well ordered and large enough to use at conventional light sources."

Researchers from Zhejiang University in China; Merck & Co.; the Center for Free Electron Laser Science at the DESY lab in Germany; and Arizona State University also contributed to the study. The work was supported by the National Institutes of Health, the National Science Foundation and the Helmholtz Association. LCLS and APS are funded by the DOE Office of Science.

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 U.S. Department of Energy Office of Science. To learn more, please visit www.slac.stanford.edu.

SLAC National Accelerator 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.