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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

AC-LGADs Fermilab front-end electronics characterization

Here, we characterized the front-end electronics used to process high-frequency signals from low-gain avalanche diodes (LGADs) at the Fermilab Test Beam Facility. LGADs are silicon detectors employed for charged particle tracking, offering exceptional spatial and temporal resolution. The purpose of this characterization was to understand how the time resolution is influenced by the front-end electronics. To achieve this, we developed a setup capable of generating input signals with varying amplitudes. The output results demonstrated that signal processing by the front-end electronics plays a crucial role in enhancing time resolution. We showed that the time resolution achieved by the FEE board is better than 2 p s at the 1 σ level.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

Asymmetric and non-stoichiometric glycoprotein recognition by two distinct antibodies results in broad protection against ebolaviruses

Several ebolaviruses cause outbreaks of severe disease. Vaccines and monoclonal antibody cocktails are available to treat Ebola virus (EBOV) infections, but not Sudan virus (SUDV) or other ebolaviruses. Current cocktails contain antibodies that cross-react with the secreted soluble glycoprotein (sGP) that absorbs virus-neutralizing antibodies. By sorting memory B cells from EBOV infection survivors, we isolated two broadly reactive anti-GP monoclonal antibodies, 1C3 and 1C11, that potently neutralize, protect rodents from disease, and lack sGP cross-reactivity. Both antibodies recognize quaternary epitopes in trimeric ebolavirus GP. 1C11 bridges adjacent protomers via the fusion loop. 1C3 has a tripartite epitope in the center of the trimer apex. One 1C3 antigen-binding fragment anchors simultaneously to the three receptor-binding sites in the GP trimer, and separate 1C3 paratope regions interact differently with identical residues on the three protomers. A cocktail of both antibodies completely protected nonhuman primates from EBOV and SUDV infections, indicating their potential clinical value.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Cellular mRNA triggers structural transformation of Ebola virus matrix protein VP40 to its essential regulatory form

The Ebola virus matrix protein VP40 forms distinct structures linked to distinct functions in the virus life cycle. Dimeric VP40 is a structural protein associated with virus assembly, while octameric, ring-shaped VP40 is associated with transcriptional control. In this study, we show that suitable nucleic acid is sufficient to trigger a dynamic transformation of VP40 dimer into the octameric ring. Deep sequencing reveals a binding preference of the VP40 ring for the 3' untranslated region of cellular mRNA and a guanine- and adenine-rich binding motif. Complementary analyses of the nucleic-acid-induced VP40 ring by native mass spectrometry, electron microscopy, and X-ray crystal structures at 1.8 and 1.4 Å resolution reveal the stoichiometry of RNA binding, as well as an interface involving a key guanine nucleotide. The host factor-induced structural transformation of protein structure in response to specific RNA triggers in the Ebola virus life cycle presents unique opportunities for therapeutic inhibition.

3′ UTR↗
DOE OSTI2022

Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies

Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structure of the Inmazeb cocktail and resistance to Ebola virus escape

Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Results for pixel and strip centimeter-scale AC-LGAD sensors with a 120 GeV proton beam

Here, we present the results of an extensive evaluation of strip and pixel AC-LGAD sensors tested with a 120 GeV proton beam, focusing on the influence of design parameters on the sensor temporal and spatial resolutions. Results show that reducing the thickness of pixel sensors significantly enhances their time resolution, with 20-μm-thick sensors achieving around 20 ps. Uniform performance is attainable with optimized n + sheet resistance, making these sensors ideal for future timing detectors. Conversely, 20-μm-thick strip sensors exhibit higher jitter than similar pixel sensors, negatively impacting time resolution, despite reduced Landau fluctuations with respect to the 50-μm-thick versions. Additionally, it is observed that a low resistivity in strip sensors limits signal size and time resolution, whereas higher resistivity improves performance. This study highlights the importance of tuning the n+ sheet resistance and suggests that further improvements should target specific applications like the Electron–Ion Collider or other future collider experiments. In addition, the detailed performance of four AC-LGADs sensor designs is reported as examples of possible candidates for specific detector applications. These advancements position AC-LGADs as promising candidates for future 4D tracking systems, pending the development of specialized readout electronics.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2026

Electron/hadron separation with the TRD based on GaAs pixel detectors

Transition Radiation Detectors (TRDs) are widely used for particle identification in both high-energy physics and astroparticle physics. They are typically equipped with gaseous detectors. The main limitation of these types of detectors is that TR photons and ionization losses cannot be decoupled, which significantly reduces the particle separation power. Recent advancements in the development of pixel detectors based on GaAs sensors offer a unique opportunity to effectively detect TR photons and separate them from ionization losses. Such detectors represent novel devices that combine precise tracking capabilities with particle identification (PID) properties. The present work is dedicated to an experimental study of particle identification properties of the TRD prototype based on 500 μ m-thick GaAs sensor bonded to a Timepix3 chip. Studies were performed at the CERN SPS and it was shown that at a particle momentum of 20 GeV/c, the probability of misidentifying a hadron as an electron is below 10 −2 for an electron detection efficiency of 98%–99%, and it is 1 . 6⋅10 −4 for electron detection efficiency of 90%. This performance surpasses the electron/hadron rejection power of all known TRDs by an order of magnitude for the same detector length.

GaAs detectors↗
DOE OSTI2025

Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane

Abstract Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP 1,2 ) are the standard of care for Ebola virus disease (EVD). Anti-GP 1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP 1,2 epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk–MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP 1,2 that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 provides therapeutic benefit at high-viremia advanced disease stages and at the lowest dose yet demonstrated for any anti-EBOV mAb-based monotherapy. The findings reported here can guide design of next-generation highly potent anti-EBOV therapeutics and vaccines.

Science & Technology - Other Topics↗
DOE OSTI2022

Glycan shield of the ebolavirus envelope glycoprotein GP

The envelope glycoprotein GP of the ebolaviruses is essential for host cell entry and the primary target of the host antibody response. GP is heavily glycosylated with up to 17 N-linked sites, numerous O-linked glycans in its disordered mucin-like domain (MLD), and three predicted C-linked mannosylation sites. Glycosylation is important for host cell attachment, GP stability and fusion activity, and shielding from neutralization by serum antibodies. Here, we use glycoproteomics to profile the site-specific glycosylation patterns of ebolavirus GP. We detect up to 16 unique O-linked glycosylation sites in the MLD, and two O-linked sites in the receptor-binding GP1 subunit. Multiple O-linked glycans are observed within N-linked glycosylation sequons, suggesting crosstalk between the two types of modifications. We confirmed C-mannosylation of W288 in full-length trimeric GP. We find complex glycosylation at the majority of N-linked sites, while the conserved sites N257 and especially N563 are enriched in unprocessed glycans, suggesting a role in host-cell attachment via DC-SIGN/L-SIGN. Our findings illustrate how N-, O-, and C-linked glycans together build the heterogeneous glycan shield of GP, guiding future immunological studies and functional interpretation of ebolavirus GP-antibody interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Suppression of neutral-pion production in deep-inelastic scattering off nuclei with the CLAS detector

We present the first threefold differential measurement for neutral-pion multiplicity ratios produced in semi-inclusive deep-inelastic electron scattering on carbon, iron, and lead nuclei normalized to deuterium from CLAS at Jefferson Lab. We found that the neutral-pion multiplicity ratio is maximally suppressed for the leading hadrons (energy fraction 𝑧 → 1), suppression varying from 25% in carbon up to 75% in lead. An enhancement of the multiplicity ratio at low 𝑧 and high 𝑝$^2_𝑇$ is observed, suggesting an interconnection between these two variables. This behavior is qualitatively similar to the previous twofold differential measurement of charged pions by the HERMES Collaboration and, recently, by CLAS Collaboration. The largest enhancement was observed at high 𝑝$^2_𝑇$ for heavier nuclei, namely, iron and lead, while the smallest enhancement was observed for the lightest nucleus, carbon. This behavior suggests a competition between partonic multiple scattering, which causes enhancement, and hadronic inelastic scattering, which causes suppression.

color confinement↗
DOE OSTI2022

Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody

Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39 Å cryo–electron microscopy structure of trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Feasibility Study of Developing Alternative Common-Cause Failure Model for Event Assessment

This report is a revision of the original report, INL/LTD-14-33376. The original report, which was a limited distribution to the Nuclear Regulatory Commission (NRC) only and not available to the public, was revised as this report for public distribution. The report presents the feasibility study of alternative common-cause failure (CCF) models that could be used for event assessment in the Standardized Plant Analysis Risk (SPAR) models. The current CCF model used by the SPAR models is the alpha factor model. The proposed alternative CCF models are the partial alpha factor model and general dependency model. These alternative CCF models are reviewed and compared to the current alpha factor model, with the partial alpha factor model being identified as the preferred CCF model that could be used for event assessment in the SPAR models.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗