Experimental drug targets HIV in a novel way

SCIENTIFIC ACHIEVEMENT

Using the Advanced Light Source (ALS), researchers from Gilead Sciences Inc. solved the structure of an experimental HIV drug bound to a novel target: the capsid protein that forms a shield around the viral RNA.

SIGNIFICANCE AND IMPACT

The work could lead to a long-lasting treatment for HIV that overcomes the problem of drug resistance and avoids the need for burdensome daily pill-taking.

Progress in HIV treatment still needed

Over the past couple of decades, safe and effective treatment for HIV infection has turned what was once a death sentence into a chronic disease. Today, people on the latest HIV drugs have near-normal life expectancy.

However, many people are still living with multidrug-resistant HIV, unable to control their virus loads with currently available HIV drugs. The virus develops resistance when people take their pills inconsistently due to forgetfulness, side effects, or a complex schedule. To some, taking a pill every day is a burden: they schedule their lives around it for fear of missing a dose. To others, it is a stigma, as it makes it difficult to hide one’s HIV status from close friends and family.

Read more on the Advanced Light Source website

Image: An experimental small-molecule drug (GS-6207) targets the protein building blocks of the HIV capsid—a conical shell (colored red in this artistic rendering) that encloses and protects the viral RNA—making the virus unable to replicate in cells. Credit Advanced Light Source

A probe of light-harvesting efficiency at the nanoscale

SCIENTIFIC ACHIEVEMENT

Using time-resolved experiments at the Advanced Light Source (ALS), researchers found a way to count electrons moving back and forth across a model interface for photoelectrochemical cells.

SIGNIFICANCE AND IMPACT

The findings provide real-time, nanoscale insight into the efficiency of nanomaterial catalysts that help turn sunlight and water into fuel through artificial photosynthesis.

Solar-fuel tech goes for gold

In the search for clean-energy alternatives to fossil fuels, one promising solution relies on photoelectrochemical (PEC) cells: water-splitting, artificial-photosynthesis devices that turn sunlight and water into solar fuels such as hydrogen. In just a decade, researchers have achieved great progress in the development of PEC systems made of light-absorbing gold nanoparticles (NPs) attached to a semiconductor film of titanium dioxide (TiO2).

Read more on the Advanced Light Source website

Image: Laser pulses were used to excite electrons in gold nanoparticles (AuNPs) on a titanium dioxide (TiO2) substrate. X-ray pulses were used to count the electrons moving between the nanoparticles and the substrate. (Credit: Oliver Gessner/Berkeley Lab)

Unexpected rise in ferroelectricity as material thins

SCIENTIFIC ACHIEVEMENT

Researchers working at the Advanced Light Source (ALS) showed that hafnium oxide surprisingly exhibits enhanced ferroelectricity (reversible electric polarization) as it gets thinner.

SIGNIFICANCE AND IMPACT

The work shifts the focus of ferroelectric studies from more complex, problematic compounds to a simpler class of materials and opens the door to novel ultrasmall, energy-efficient electronics.

Ferroelectric lower limit?

Distortions in the atomic geometries of certain materials can lead to ferroelectricity—the presence of electric dipoles (charge separations) with switchable polarizations. The ability to control this polarization with an external voltage offers great promise for ultralow-power microprocessors and nonvolatile memory.

As electronic devices become smaller, however, the materials used to store and manipulate electronic data are being pushed to low-dimensional extremes. Properties that function reliably in bulk materials often diminish in ultrathin films just a few atomic units thick. Therefore, exploring the critical thickness limit in “polar” materials (i.e., materials having spontaneous electric polarization) is not only a fundamental issue for nanoscale ferroelectric research, it also has extensive implications for the future of high-density ferroelectric-based electronics.

Read more on Advanced Light Source (ALS) website

Image : A thin layer of hafnium oxide (two unit-cell thicknesses, or about 1 nm) has an electric polarization that’s reversible by an external electric field, making it attractive for use in next-generation low-power microelectronics.

Credit: Ella Maru Studio

A scalable platform for two-dimensional metals

SCIENTIFIC ACHIEVEMENT

Using a new method for stabilizing a two-dimensional (2D) metal on a large-area platform, researchers probed the origins of the material’s superconductivity at the Advanced Light Source (ALS).

SIGNIFICANCE AND IMPACT

The work represents a notable milestone in advancing 2D materials toward broad applications in topological computing, advanced optics, and molecular sensing.

Expanding the scientific palette

If you confine everyday metals to layers only a few atoms thick, they acquire new properties that are different from those exhibited by their more common bulk forms. The ability to synthesize such two-dimensional (2D) metals means that the range of materials available for novel uses can be expanded to different areas of the periodic table—providing a much richer “scientific palette” of properties for applications in topological computing, advanced optics, and molecular sensing.

Read more on the ALS website

Image: A confined layer of metal atoms (silver spheres) on a silicon carbide (SiC) substrate is capped by a layer of graphene, allowing for new forms of low-dimensional metals with unique properties. Gold spheres represent Cooper pairs, responsible for conventional superconductivity. 

Credit: Yihuang Xiong/Penn State

Assembly lines for designer bioactive compounds

Researchers successfully bioengineered changes to a molecular “assembly line” for bioactive compounds, based in part on insights gained from small-angle x-ray scattering at the Advanced Light Source (ALS).

The ability to re-engineer these assembly lines could improve their performance and facilitate the synthesis of new medically useful compounds.

Microbes are known to possess molecular “assembly lines” that produce an important class of compounds, many of which have uses as antibiotics, antifungals, and immunosuppressants. The compounds are peptides—chains of amino acids like RNA, but shorter and produced, not by ribosomes, but by cellular machines known as nonribosomal peptide synthetases (NRPSs).

>Read more on the Advanced Light Source website

Image: Top: Comparison of experimental SAXS scattering data (black) with theoretical curves (green) obtained using an ensemble optimization method (EOM) shows excellent agreement. Bottom: LgrA structural models corresponding to the EOM analyses show large differences in conformation, similar to the differences observed using crystallography.

Seeing “under the hood” in batteries

From next-gen smartphones to longer-range electric cars and an improved power grid, better batteries are driving tech innovation. And to push batteries beyond their present-day performance, researchers want to see “under the hood” to learn how the individual ingredients of battery materials behave beneath the surface.

This could ultimately lead to battery improvements such as increased capacity and voltage.

But many of the techniques scientists use can only scratch the surface of what’s at work inside batteries, and a high-sensitivity X-ray technique at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) is attracting a growing group of scientists because it provides a deeper, more precise dive into battery chemistry.

>Read more on the Advaced Light Source at LBNL website

Image: The high-efficiency RIXS system at the Advanced Light Source’s Beamline 8.0.1
Credit: Marilyn Sargent/Berkeley Lab

How a new electrocatalyst enables ultrafast reactions

The work provides rational guidance for the development of better electrocatalysts for applications such as hydrogen-fuel production and long-range batteries for electric vehicles.

The oxygen evolution reaction (OER) is the electrochemical mechanism at the heart of many processes relevant to energy storage and conversion, including the splitting of water to generate hydrogen fuel and the operation of proposed long-range batteries for electric vehicles. Because the OER rate is a limiting factor in such processes, highly active OER electrocatalysts with long-term stability are being sought to increase reaction rates, reduce energy losses, and improve cycling stability. Catalysts incorporating rare and expensive materials such as iridium and ruthenium exhibit good performance, but an easily prepared, efficient, and durable OER catalyst based on earth-abundant elements is still needed for large-scale applications.

Key insight: shorter O-O bonds
In an earlier study, a group led by John Goodenough (2019 Nobel laureate in chemistry) measured the OER activities of two compounds with similar structures: CaCoO3 and SrCoO3. They found that the CaCoO3 exhibited higher OER activity, which they attributed to its shorter oxygen–oxygen (O-O) bonds. Inspired by this, members of the Goodenough group have now analyzed a metallic layered oxide, Na0.67CoO2, which has an even more compact structure than CaCoO3. X-ray diffraction (XRD) experiments performed at the Advanced Photon Source (APS) confirmed that the shortest O-O separation in Na0.67CoO2 is 2.30 Å, compared to 2.64 Å for CaCoO3. The researchers then compared the OER performance of Na0.67CoO2 with IrO2, Co3O4, and Co(OH)2. They found that Na0.67CoO2 exhibited the highest current density, the lowest overpotential (a measure of thermodynamic energy loss), and the most favorable Tafel slope (sensitivity of the electric current to applied potential). The Na0.67CoO2 also showed excellent stability under typical operating conditions.

>Read more on the Advanced Light Source website

Image: (extract, full image here) A new electrocatalyst prepared for this study, Na0.67CoO2, consists of two-dimensional CoO2 layers separated by Na layers (not shown). The Co ions (blue spheres) have four different positions (Co1-Co4), and the distorted Co–O octahedra have varying oxygen–oxygen (O-O) separations (thick red lines connecting red spheres). All of the O-O bonds are shorter than 2.64 Å (the length of the corresponding bonds in a comparable material), and the shortest bonds are less than 2.40 Å. It turns out that O-O separation has a strong effect on the oxygen evolution reaction (OER) in this material.

Water improves material’s ability to capture CO2

With the help of the Advanced Light Source (ALS), researchers from UC Berkeley and ExxonMobil fine-tuned a material to capture CO2 in the presence of water.

About 65% of anthropogenic greenhouse gas emissions comes from the combustion of fossil fuels in power plants. So far, efforts to capture CO2 from power-plant flue gases and sequester it underground have mainly focused on coal-fired power plants. However, in the United States, natural gas has surpassed coal in the amount CO2 released, despite the fact that natural gas emits approximately half as much CO2 per unit of electricity. Therefore, new materials are urgently needed to address this situation.

Not all combustion is alike

Compared to coal-fired power plants, natural gas combined cycle (NGCC) plants produce flue gases with low CO2 concentrations. This reduces the carbon footprint, but increases the technical difficulty of CO2 capture. Also, materials capable of adsorbing such low concentrations of CO2 often require high temperatures to release it for sequestration, an important part of the cycle that offsets initial low-carbon benefits. NGCC emissions also have a higher concentration of O2, which has a corrosive effect on adsorbent materials, and both NGCC and coal flue streams are saturated in water, which can both degrade materials and reduce efficiency. Thus, an effective NGCC CO2-capture material must selectively bind low-concentration CO2 under humid conditions while being thermally and oxidatively stable.

>Read more on the Advanced Light Source website

Image: Single-crystal x-ray diffraction enables the precise determination of the positions of the atoms in metal–organic frameworks (MOFs), highly porous materials capable of soaking up vast quantities of a specific gas molecule, such as CO2. This structure represents 2-ampd–Zn2(dobpdc), a MOF with the same structure as 2-ampd–Mg2(dobpdc), the subject of this study. Light blue, blue, red, gray, and white spheres represent Zn, N, O, C, and H atoms, respectively.

ALS reveals vulnerability in cancer-causing protein

A promising anticancer drug, AMG 510, was developed by Amgen with the help of novel structural insights gained from protein structures solved at the Advanced Light Source (ALS).

Mutations in a signaling protein, KRAS, are known to drive many human cancers. One specific KRAS mutation, KRAS(G12C), accounts for approximately 13% of non-small cell lung cancers, 3% to 5% of colorectal cancers, and 1% to 2% of numerous other solid tumors. Approximately 30,000 patients are diagnosed each year in the United States with KRAS(G12C)-driven cancers.

Despite their cancer-triggering significance, KRAS proteins have for decades resisted attempts to target their activity, leading many to regard these proteins as “undruggable.” Recently, however, a team led by researchers from Amgen identified a small molecule capable of inhibiting the activity of KRAS(G12C) and driving anti-tumor immunity. Protein crystallography studies at the ALS provided crucial information about the structural interactions between the potential drug molecule and KRAS(G12C).

>Read more on the Advanced Light Source website

Image: A structural map of KRAS(G12C), showing the AMG 510 molecule in the binding pocket. The yellow region depicts where AMG 510 covalently attaches to the KRAS protein.
Credit: Amgen

New catalyst resists destructive carbon buildup in electrodes

Key challenges in the transition to sustainable energy include the long-duration storage of cheap, renewable electricity and the electrification of the heavy-freight transportation sector. Both challenges can be met using electrochemical cells. Solid oxide electrolysis cells are capable of highly efficient splitting of steam and CO2 to produce a synthetic H2–CO gas mixture (syngas), which can be converted into synthetic hydrocarbon transportation fuels using conventional industrial reactors. However, the efficiency of the process is limited by the risk of destructive carbon deposition inside the cells’ porous solid electrodes. A nickel catalyst is responsible for the carbon growth, but replacing this long-standing conventional catalyst has turned out to be highly challenging.

Now, researchers have used ambient-pressure x-ray photoelectron spectroscopy (APXPS) at ALS Beamlines 9.3.2 and 11.0.2 to probe the mechanisms by which carbon grows on different catalysts during CO2 electrolysis. Gadolinium-doped cerium oxide (GDC) is known to resist carbon growth, and the ambient-pressure experiments probed the degree and mechanism of this carbon resistance. The experimental data, subsequently confirmed by density functional theory calculations, revealed that the carbon atoms are energetically trapped by various oxygen species on the surface of GDC—a capability entirely lacking for nickel.

>Read more on the Advanced Light Source website

Image: Artistic representation of a nickel-based electrode as a broken down fuel pump and of a cerium-based electrode as a new, productive pump. Credit: Cube3D

Milestone in ALS-Upgrade project will bring in a new ring

Construction of innovative accumulator ring as part of ALS-U project will keep Berkeley Lab at the forefront of synchrotron light source science.

An upgrade of the Advanced Light Source (ALS) at the U.S. Department of Energy’s (DOE’s) Lawrence Berkeley National Laboratory (Berkeley Lab) has passed an important milestone that will help to maintain the ALS’ world-leading capabilities.

On Dec. 23 the DOE granted approval for a key funding step that will allow the project to start construction on a new inner electron storage ring. Known as an accumulator ring, this inner ring will feed the upgraded facility’s main light-producing storage ring, and is a part of the upgrade project (ALS-U).

This latest approval, known as CD-3a, authorizes an important release of funds that will be used to purchase equipment and formally approves the start of construction on the accumulator ring.

>Read more on the Advanced Light Source at Berkeley Lab website

Image: This cutaway rendering of the Advanced Light Source dome shows the layout of three electron-accelerating rings. A new approval step in the ALS Upgrade project will allow the installation of the middle ring, known as the accumulator ring.
Credit: Matthaeus Leitner/Berkeley Lab

Egyptian mummy bones explored with X-rays and infrared light

Researchers from Cairo University work with teams at Berkeley Lab’s Advanced Light Source to study soil and bone samples dating back 4,000 years.

Experiments at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) are casting a new light on Egyptian soil and ancient mummified bone samples that could provide a richer understanding of daily life and environmental conditions thousands of years ago.
In a two-monthslong research effort that concluded in late August, two researchers from Cairo University in Egypt brought 32 bone samples and two soil samples to study using X-ray and infrared light-based techniques at Berkeley Lab’s Advanced Light Source (ALS). The ALS produces various wavelengths of bright light that can be used to explore the microscopic chemistry, structure, and other properties of samples.
Their visit was made possible by LAAAMP – the Lightsources for Africa, the Americas, Asia and Middle East Project – a grant-supported program that is intended to foster greater international scientific opportunity and collaboration for scientists working in that region of the globe.

>Read more on the Advanced Light Source (Berkeley Lab) website

Image: From left, Cairo University postdoctoral researcher Mohamed Kasem, ALS scientist Hans Bechtel, and Cairo University associate professor Ahmed Elnewishy study bone samples at the ALS using infrared light.
Credit: Marilyn Sargent/Berkeley Lab

Machine learning enhances light-beam performance at the ALS

Successful demonstration of algorithm by Berkeley Lab-UC Berkeley team shows technique could be viable for scientific light sources around the globe.

Synchrotron light sources are powerful facilities that produce light in a variety of “colors,” or wavelengths – from the infrared to X-rays – by accelerating electrons to emit light in controlled beams.
Synchrotrons like the Advanced Light Source at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) allow scientists to explore samples in a variety of ways using this light, in fields ranging from materials science, biology, and chemistry to physics and environmental science. Researchers have found ways to upgrade these machines to produce more intense, focused, and consistent light beams that enable new, and more complex and detailed studies across a broad range of sample types. But some light-beam properties still exhibit fluctuations in performance that present challenges for certain experiments.

Image: This image shows the profile of an electron beam at Berkeley Lab’s Advanced Light Source synchrotron, represented as pixels measured by a charged coupled device (CCD) sensor. When stabilized by a machine-learning algorithm, the beam has a horizontal size dimension of 49 microns (root mean squared) and vertical size dimension of 48 microns (root mean squared). Demanding experiments require that the corresponding light-beam size be stable on time scales ranging from less than seconds to hours to ensure reliable data.
Credit: Lawrence Berkeley National Laboratory

Multimodal study of ion-conducting membranes

Using multiple x-ray characterization tools, researchers showed how chemical and structural changes improve the performance of a novel ion-conducting polymer (ionomer) membrane from 3M Company.

In fuel cells (which generate clean power from hydrogen fuel) and electrolyzers (water-splitting devices that produce hydrogen fuel), positive and negative electrodes are separated by membranes composed of ion-conducting polymers (ionomers). These membranes prevent contact between the electrodes—thus avoiding catastrophic failure—while allowing selective passage of ions to complete the circuit.

Generally, such membranes are based on a class of perfluorosulfonic acid (PFSA) ionomers with remarkable proton conductivity and stability. Recently, however, companies such as 3M have been developing new ionomers with improved performance. In this work, researchers took a closer look at the structural and chemical properties of these materials at the nanometer scale. The resulting insights provide valuable guidance on design strategies for optimally performing ionomers.

>Read more on the Advanced Light Source website

Image: Resonant x-ray scattering (RXS) and x-ray absorption spectroscopy (XAS) with elemental sensitivity unravel structural features and chemical factors affecting morphology and ion transport in proton-conducting membranes.

A citizen-science computer game for protein design

Using the computer game, “Foldit,” nonexpert citizen scientists designed new proteins whose structures, verified at the Advanced Light Source (ALS), were equivalent in quality to and more structurally diverse than computer-generated designs.

Proteins constitute the biomachinery—the cellular gears and levers—that make our bodies work. When this machinery is running smoothly, nutrients get absorbed, cells regenerate, and so on. When the machinery breaks down, the tools needed to fix the problem (i.e. drug molecules) are often proteins themselves.

Until recently, the pool of proteins available for such therapeutic purposes was limited to those found in nature. But natural proteins represent a small subset of all the possible ways to link 20 amino acids—the basic building blocks of all proteins—into chains hundreds, even thousands, of units long. On top of this, there are countless ways in which any given protein chain can fold—a key aspect of functionality.

In the last 20 years, “de novo” protein design (from scratch as opposed to starting with a known protein) has taken off, promising cheap and effective drugs with fewer side effects. But given the huge number of possibilities available, scientists are limited in their ability to fully explore this vast “protein space.”

>Read more on the Advanced Light Source website on Berkeley Lab

Image: The user interface of Foldit, a free online computer game developed to crowdsource problems in protein modeling. (a) The Foldit score: better models yield higher scores. (b) The design palette allows players to change the amino acids in the protein chain. (c) The “pull” tool allows players to manipulate the 3D structure of the model. (d) The “undo” graph tracks the score as a model is developed and allows players to backtrack. (e) Additional tool selections.

Study reveals ‘radical’ wrinkle in forming complex carbon molecules in space

Unique experiments at Berkeley Lab’s Advanced Light Source shine a light on a new pathway for carbon chemistry to evolve in space.

A team of scientists has discovered a new possible pathway toward forming carbon structures in space using a specialized chemical exploration technique at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). The team’s research has now identified several avenues by which ringed molecules known as polycyclic aromatic hydrocarbons, or PAHs, can form in space. The latest study is a part of an ongoing effort to retrace the chemical steps leading to the formation of complex carbon-containing molecules in deep space. PAHs – which also occur on Earth in emissions and soot from the combustion of fossil fuels – could provide clues to the formation of life’s chemistry in space as precursors to interstellar nanoparticles. They are estimated to account for about 20 percent of all carbon in our galaxy, and they have the chemical building blocks needed to form 2D and 3D carbon structures.

>Read more on the ALS at Berkeley Lab website

Image: This composite image shows an illustration of a carbon-rich red giant star (middle) warming an exoplanet (bottom left) and an overlay of a newly found chemical pathway that could enable complex carbons to form near these stars.
Credits: ESO/L. Calçada; Berkeley Lab, Florida International University, and University of Hawaii at Manoa.