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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Proteomic Analysis of Exosomes for Discovery of Protein Biomarkers for Prostate and Bladder Cancer

Extracellular vesicles (EVs) are released by nearly all cell types as part of normal cell physiology, transporting biological cargo, including nucleic acids and proteins, across the cell membrane. In pathological states such as cancer, EV-derived cargo may mirror the altered state of the cell of origin. Exosomes are the smaller, 50–150 nanometer-sized EVs released from fusion of multivesicular endosomes with the plasma membrane. Exosomes play important roles in cell-cell communication and participate in multiple cancer processes, including invasion and metastasis. Therefore, proteomic analysis of exosomes is a promising approach to discover potential cancer biomarkers, even though it is still at an early stage. Herein, we critically review the advances in exosome isolation methods and their compatibility with mass spectrometry (MS)-based proteomic analysis, as well as studies of exosomes in pathogenesis and progression of prostate and bladder cancer, two common urologic cancers whose incidence rates continue to rise annually. As urological tumors, both urine and blood samples are feasible for noninvasive or minimally invasive analysis. A better understanding of the biological cargo and functions of exosomes via high-throughput proteomics will help provide new insights into complex alterations in cancer and provide potential therapeutic targets and personalized treatment for patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

The effect of water on colloidal quantum dot solar cells

Almost all surfaces sensitive to the ambient environment are covered by water, whereas the impacts of water on surface-dominated colloidal quantum dot (CQD) semiconductor electronics have rarely been explored. Here, strongly hydrogen-bonded water on hydroxylated lead sulfide (PbS) CQD is identified. The water could pilot the thermally induced evolution of surface chemical environment, which significantly influences the nanostructures, carrier dynamics, and trap behaviors in CQD solar cells. The aggravation of surface hydroxylation and water adsorption triggers epitaxial CQD fusion during device fabrication under humid ambient, giving rise to the inter-band traps and deficiency in solar cells. To address this problem, meniscus-guided-coating technique is introduced to achieve dense-packed CQD solids and extrude ambient water, improving device performance and thermal stability. Our works not only elucidate the water involved PbS CQD surface chemistry, but may also achieve a comprehensive understanding of the impact of ambient water on CQD based electronics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Molecular characterization of a fungal gasdermin-like protein

Programmed cell death (PCD) in filamentous fungi prevents cytoplasmic mixing following fusion between conspecific genetically distinct individuals (allorecognition) and serves as a defense mechanism against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (i.e., senescence plasmids). Recently, we identified regulator of cell death-1 ( rcd-1 ), a gene controlling PCD in germinated asexual spores in the filamentous fungus Neurospora crassa . rcd-1 alleles are highly polymorphic and fall into two haplogroups in N. crassa populations. Coexpression of alleles from the two haplogroups, rcd-1–1 and rcd-1–2 , is necessary and sufficient to trigger a cell death reaction. Here, we investigated the molecular bases of rcd-1 -dependent cell death. Based on in silico analyses, we found that RCD-1 is a remote homolog of the N-terminal pore-forming domain of gasdermin, the executioner protein of a highly inflammatory cell death reaction termed pyroptosis, which plays a key role in mammalian innate immunity. We show that RCD-1 localizes to the cell periphery and that cellular localization of RCD-1 was correlated with conserved positively charged residues on predicted amphipathic α-helices, as shown for murine gasdermin-D. Similar to gasdermin, RCD-1 binds acidic phospholipids in vitro, notably, cardiolipin and phosphatidylserine, and interacts with liposomes containing such lipids. The RCD-1 incompatibility system was reconstituted in human 293T cells, where coexpression of incompatible rcd-1–1/rcd-1–2 alleles triggered pyroptotic-like cell death. Oligomers of RCD-1 were associated with the cell death reaction, further supporting the evolutionary relationship between gasdermin and rcd-1 . This report documents an ancient transkingdom relationship of cell death execution modules involved in organismal defense.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A small-angle neutron scattering study of the physical mechanism that drives the action of a viral fusion peptide

Viruses have evolved a variety of ways for delivering their genetic cargo to a target cell. One mechanism relies on a short sequence from a protein of the virus that is referred to as a fusion peptide. In some cases, the isolated fusion peptide is also capable of causing membranes to fuse. Infection by HIV-1 involves the 23 amino acid N-terminal sequence of its gp41 envelope protein, which is capable of causing membranes to fuse by itself, but the mechanism by which it does so is not fully understood. In this study, a variant of the gp41 fusion peptide that does not strongly promote fusion was studied in the presence of vesicles composed of a mixture of unsaturated lipids and cholesterol by small-angle neutron scattering and circular dichroism spectroscopy to improve the understanding of the mechanism that drives vesicle fusion. The peptide concentration and cholesterol content govern both the peptide conformation and its impact on the bilayer structure. The results indicate that the mechanism that drives vesicle fusion by the peptide is a strong distortion of the bilayer structure by the peptide when it adopts the β-sheet conformation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Investigation of warm dense matter by combining static and dynamic compression

Shock-compressing material samples that are precompressed with diamond-anvil cells (DACs) enables benchmarking equation of state measurements over a wide range of high-pressure conditions, in particular, warm dense matter relevant to planetary science, astrophysics, and inertial confinement fusion. These targets provide optical access to the shocked sample, so optical velocity interferometry and pyrometry are typical diagnostics. We present a scaling for the coupling of the laser drive to the shock pressure in DACs based on over 150 prior experiments that can be used to design future experiments. For initial static pressures ≤ 5 GPa, using a sapphire window mitigates the effect of photoionization compared to diamond windows and allows the measurement of shock pressures up to 1 TPa with optical diagnostics.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2024

Laser-to-proton conversion efficiency studies for proton fast ignition

We assess the conversion efficiency from intense picosecond laser pulses to multi-MeV ion beams for a wide range of laser and target parameters, using 2D kinetic particle-in-cell simulations. Scalings are addressed in a quasi-one-dimensional geometry, leaving out beam divergence. Then, we study the conversion efficiency into a narrow spatial band along the laser axis for flat and hemispherical targets in large-scale 2D simulations. Combining these findings allows us to calculate the energy requirements for ignition of a compressed ICF target with an intense proton beam in a fast-ignition scenario.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2023

Molecular Beam Epitaxy of Monocrystalline GaAs on Water-Soluble NaCl Thin Films

The goal of this project was to demonstrate the feasibility of employing an epitaxial NaCl thin film as a water-soluble release layer for III-V photovoltaic devices and GaAs substrate reuse. Over the course of this project efforts were focused on: 1) achieving crystalline NaCl thin films on GaAs (100) substrate, 2) exploring the growth parameters for subsequent GaAs on NaCl thin films in effort to improve crystallinity of the semiconductor layer, 3) deposition and removal of single crystalline solar cell devices from the parent substrate, and 4) improving morphology and reducing large scale defects in the removed layers to fabricate a working a solar cell device. There was no previous work on direct integration of GaAs/NaCl/GaAs heterostructures at the time of this study. We used molecular beam epitaxy (MBE) to deposit both the alkali halide salt and subsequent III-V material in the same chamber, with no vacuum break. Single crystalline GaAs films were achieved on NaCl layers through careful tuning of the growth parameters and exposure to the reflection high energy electron diffraction (RHEED) beam. Dissolution of the NaCl layer in water provided rapid release of the semiconductor layer from the substrate. Monocrystalline solar cells were grown on the III-V templates using MBE and dynamic hydride vapor phase epitaxy (HVPE). However, the extended time at elevated temperatures required for the cell growth resulted in large area defects from fusion of the semiconductor overlayer to the substrate, causing shorts in fabricated devices. By changing the way that the template layer was grown, the density of these defects could be reduced. Unfortunately, the defects were not reduced to a level allowing for fabrication of a working device.

14 SOLAR ENERGY↗
DOE OSTI2026

The Development of Kinetic and Radiation Hydrodynamics Modeling of Thermonuclear Burn Propagation in Isochoric p - 11 B Through the Support of the INFUSE Program

The report summarizes DOE INFUSE-supported work between HB11 Energy and the University of Rochester’s TriForce Institute to improve computational modeling of advanced fusion fuels, especially proton–boron-11 (p- 11 B). The project extended the TriForce particle-in-cell/Monte Carlo collision code to include physics needed for dense, high-temperature p- 11 B burn studies, including p- 11 B fusion reactions, three-alpha-particle reaction products, relativistic Coulomb collisions, large-angle nuclear scattering, bremsstrahlung radiation, inverse bremsstrahlung absorption, and photon transport. The upgraded models were verified against focused physics tests and against known deuterium–tritium burn behavior. The study then used one-dimensional spherical simulations to estimate the conditions required for thermonuclear burn propagation in isochoric p- 11 B fuel. The calculations found that burn propagation is possible in the model, but only under very extreme hot-spot conditions, such as about 7000 g/cm 3 at 500 keV or 9000 g/cm 3 at 300 keV for a 20-micron hot spot. These conditions are much more demanding than current demonstrated inertial confinement fusion hot spots. The report concludes that the INFUSE collaboration successfully advanced kinetic and radiation modeling capabilities for p- 11 B fusion and provided useful estimates of ignition requirements. However, the simulated fuel gains remain below what would be needed for practical inertial fusion energy, and further work is needed to reconcile differences among kinetic, radiation-hydrodynamic, and analytic models and to identify more achievable target designs.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2023

Evolution and hot electron generation of laser–plasma instabilities in direct-drive inertial confinement fusion

A series of 2D in-plane plane wave particle-in-cell simulations find distinctive paths of laser-plasma instability evolution in OMEGA-scale implosions, depending on the initial electron temperature. At low temperatures, two-plasmon decay (TPD) dominates in both initial growth and the steady state. At high temperatures, the initial dominant modes switch to stimulated Raman scattering, but TPD still dominates a steady state characterized by cavitation and Langmuir turbulence. A hot electron scaling is also obtained from the simulations that, when combined with laser/plasma conditions from hydro simulations, can predict hot electron generation in implosions that do not employ smoothing-by-spectral-dispersion (SSD). It also shows that under the same laser/plasma conditions, SSD can reduce hot electron generation.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2026

Rerouting reductant flux via protein tethering enhances biohydrogen production in Thermococcus kodakarensis

Microbes that generate copious amounts of hydrogen (H 2 ) via dark fermentation are a promising means to evolve and improve renewable biofuels. Many anaerobic hyperthermophilic archaea, such as the fast-growing, genetically tractable, heterotroph Thermococcus kodakarensis, produce generous quantities of H2 and provide an idealized platform to further optimize naturally high levels of biohydrogen reduction. Precise genetic manipulations and modifications to growth conditions have already resulted in substantial increases to H2 output but additional improvements are desired. An unexamined and potentially valuable route towards increased H 2 production is to tether select electron donor and acceptor proteins together to reroute and maximize the flow of electrons towards H 2 production. Such strategies have shown promise in Bacteria and Eukarya but have not yet been investigated in thermophilic Archaea. Here, we generate and evaluate twelve novel T. kodakarensis strains wherein a proteinaceous electron carrier (a ferredoxin, Fd) is physically tethered to the membrane-bound-hydrogenase (MBH), the sole H 2 producing enzyme, to direct electron flux towards biohydrogen generation. Growth assessments and H 2 output measurements demonstrate that strains encoding protein-fusions evolve up to ~ 40% more H2 per cell than the host strain. Eliminating H 2 consumption and alternative routes of electron sinks in concert with protein tethering further increased H2 output per cell for a maximum increase of ~ 66% over the host strain. Our results demonstrate that rerouting electron flux via protein tethering coupled with the elimination of reductant sinks is a promising means towards improved biohydrogen production in T. kodakarensis. KEY POINTS: Protein tethering between redox proteins can reroute electron flux in vivo. Enforced protein proximity results in ~ 40% increases in H2 production per cell. Protein-tethering provides a generalizable framework to redirect redox metabolism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain. The crystal structures of ASH1L-inhibitor complexes reveal compound binding to the autoinhibitory loop region in the SET domain. When tested in MLL leukemia models, our lead compound, AS-99, blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo. This work validates the ASH1L SET domain as a druggable target and provides a chemical probe to further study the biological functions of ASH1L as well as to develop therapeutic agents.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Investigation of boosted proton energies through proton radiography of target normal sheath acceleration fields in the multi-ps regime

Multi-kilojoule, multi-picosecond short-pulse lasers, such as the National Ignition Facility-Advanced Radiographic Capability laser and the OMEGA-Extended Performance laser, which have been constructed over the last two decades, enable exciting opportunities to produce high-brightness, high-energy laser-driven proton sources for applications in high-energy-density science like proton fast ignition for inertial fusion energy, particle radiography, and materials science studies. Results on these platforms have demonstrated enhanced accelerated proton energies and electron temperatures when compared to established scaling laws. Recent work has developed a new scaling for proton TNSA in the multi-ps regime. However, this new physics in the multi-ps regime motivates the need to understand the origin of the enhancement in proton energies. Toward this goal, here this work presents the first measurements of the TNSA accelerating sheath field in the multi-ps regime for pulse durations of 0.6, 5, and 10 ps. This measurement was achieved by using a separate TNSA proton source to radiograph the spatiotemporal profile of the accelerating sheath that is responsible for proton acceleration. The use of stacked radiochromic film detectors allows for a discrete time profile of the radiographs, thus enabling the measurement of the temporal and spatial evolution of the accelerating field. In performing this measurement, we extract quantities such as the sheath strength as a function of time and pulse duration, which shows that longer pulse durations sustain a stronger electric field for a longer duration when compared to sub-ps laser pulses, which may enable the observed boosted proton energies and proton conversion efficiencies.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2026

Plasma Surface Interactions: Predicting the Performance and Impact of Dynamic PFC Surfaces

This project focused on the development and integration of high-performance simulation tools to predict the operating behavior of Plasma-Facing Components in magnetic confinement fusion systems. A key objective at Illinois was to assess the impact of the dynamic interplay between the evolving material surface and the magnetized plasma sheath, and characterize the impact of tungsten-based PFCs on plasma contamination, including phenomena such as surface erosion, dynamic recycling of fuel species, and tritium retention, which are critical for the success of future magnetic fusion devices.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
NASA NTRS1984

Fabrication of glass gas cells for the HALOE and MAPS satellite experiments

The Halogen Occultation Experiment (HALOE) and the Measurement of Air Pollution from Satellites (MAPS) experiment are satellite-borne experiments which measure trace constituents in the Earth's atmosphere. The instruments which obtain the data for these experiments are based on the gas filter correlation radiometer measurement technique. In this technique, small samples of the gases of interest are encapsulated in glass cylinders, called gas cells, which act as very selective optical filters. This report describes the techniques employed in the fabrication of the gas cells for the HALOE and MAPS instruments. Details of the method used to fuse the sapphire windows (required for IR transmission) to the glass cell bodies are presented along with detailed descriptions of the jigs and fixtures used during the assembly process. The techniques and equipment used for window inspection and for pairing the HALOE windows are discussed. Cell body materials and the steps involved in preparing the cell bodies for the glass-to-sapphire fusion process are given.

Sullivan, E. M.↗
DOE OSTI2021

Cyanobacteriochromes active in the far-red to near-infrared

The present invention provides a protein fusion construct comprising a far-red cyanobacteriochrome (CBCR) domain linked to a heterologous domain, wherein the far-red CBCR domain comprises a CBCR polypeptide and a tetrapyrrole chromophore. The invention also provides nucleic acids, expression cassettes, vectors, and host cells for expression of the far-red CBCR protein fusion constructs. Methods for detecting cellular components, methods for imaging biological structures, and method for modulating cellular processes using the protein fusion constructs are also provided.

Lagarias, John Clark↗
NASA NTRS2003

The TP53 dependence of radiation-induced chromosome instability in human lymphoblastoid cells

The dose and TP53 dependence for the induction of chromosome instability were examined in cells of three human lymphoblastoid cell lines derived from WIL2 cells: TK6, a TP53-normal cell line, NH32, a TP53-knockout created from TK6, and WTK1, a WIL2-derived cell line that spontaneously developed a TP53 mutation. Cells of each cell line were exposed to (137)Cs gamma rays, and then surviving clones were isolated and expanded in culture for approximately 35 generations before the frequency and characteristics of the instability were analyzed. The presence of dicentric chromosomes, formed by end-to-end fusions, served as a marker of chromosomal instability. Unexposed TK6 cells had low levels of chromosomal instability (0.002 +/- 0.001 dicentrics/cell). Exposure of TK6 cells to doses as low as 5 cGy gamma rays increased chromosome instability levels nearly 10-fold to 0.019 +/- 0.008 dicentrics/cell. There was no further increase in instability levels beyond 5 cGy. In contrast to TK6 cells, unexposed cultures of WTK1 and NH32 cells had much higher levels of chromosome instability of 0.034 +/- 0.007 and 0.041 +/- 0.009, respectively, but showed little if any effect of radiation on levels of chromosome instability. The results suggest that radiation exposure alters the normal TP53-dependent cell cycle checkpoint controls that recognize alterations in telomere structure and activate apoptosis.

Non-NASA Center↗
DOE OSTI2022

SARS-CoV-2 spike protein variant binding affinity to an angiotensin-converting enzyme 2 fusion glycoproteins

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the Coronavirus disease 2019 (Covid-19) pandemic, continues to evolve and circulate globally. Current prophylactic and therapeutic countermeasures against Covid-19 infection include vaccines, small molecule drugs, and neutralizing monoclonal antibodies. SARS-CoV-2 infection is mainly mediated by the viral spike glycoprotein binding to angiotensin converting enzyme 2 (ACE2) on host cells for viral entry. As emerging mutations in the spike protein evade efficacy of spike-targeted countermeasures, a potential strategy to counter SARS-CoV-2 infection is to competitively block the spike protein from binding to the host ACE2 using a soluble recombinant fusion protein that contains a human ACE2 and an IgG1-Fc domain (ACE2-Fc). Here, we have established Chinese Hamster Ovary (CHO) cell lines that stably express ACE2-Fc proteins in which the ACE2 domain either has or has no catalytic activity. The fusion proteins were produced and purified to partially characterize physicochemical properties and spike protein binding. Our results demonstrate the ACE2-Fc fusion proteins are heavily N-glycosylated, sensitive to thermal stress, and actively bind to five spike protein variants (parental, alpha, beta, delta, and omicron) with different affinity. Our data demonstrates a proof-of-concept production strategy for ACE2-Fc fusion glycoproteins that can bind to different spike protein variants to support the manufacture of potential alternative countermeasures for emerging SARS-CoV-2 variants.

60 APPLIED LIFE SCIENCES↗