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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Lipid accumulation-induced hepatocyte senescence regulates the activation of hepatic stellate cells through the Nrf2-antioxidant response element pathway

Highlights: • Oxidative stress caused by lipid deposition causes hepatocyte senescence. • Free fatty acid-induced senescent hepatocytes promote hepatic stellate cell activation and development of hepatic fibrosis. • Senescent hepatocytes regulate hepatic fibrosis through the Nrf2-antioxidant response element pathway. Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease globally. Elderly individuals are at a higher risk of developing NAFLD with severe clinical outcomes. Although NAFLD is closely related to liver aging, the role of hepatocyte senescence in the progression of NAFLD, especially in the development of fibrosis, is still unclear. The early stage of NAFLD is mainly characterized by lipid accumulation in hepatocytes, which could lead to severe oxidative stress, causing cellular senescence. In the present study, hepatocytes cultured in the presence of free fatty acids to induce lipid deposition were used as a hepatocyte senescence model in vitro. Senescent hepatocytes significantly increased the activation of co-cultured primary hepatic stellate cells (HSCs) and the expression of pro-fibrosis molecules. Moreover, the antioxidant regulator nuclear factor erythroid 2-related factor 2 (Nrf2) that was upregulated in senescent hepatocytes was found to be related to the activation of co-cultured HSCs. The Nrf2 agonist sulforaphane, which upregulated the transcriptional activity of the Nrf2-antioxidant response element (ARE) pathway, remarkably inhibited hepatocyte senescence and its activation effect on HSCs. However, the liver tissue obtained from non-alcoholic steatohepatitis (NASH) mice with Nrf2 knockdown showed decreased antioxidation and significant liver senescence and fibrosis. In conclusion, this study confirmed that lipid accumulation induces hepatocyte senescence, which leads to HSC activation and development of hepatic fibrosis. Increasing the activity of the Nrf2-ARE antioxidant pathway in senescent hepatocytes elicited the opposite effect, suggesting that targeting Nrf2 may prevent or delay the progression of aging-related liver fibrosis in NASH.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

Herein, a copper-mediated radiobromination of (hetero)aryl boronic pinacol esters is described. Cyclotron-produced [76/77Br]bromide was isolated using an anion exchange cartridge, wherein the pre-equilibration and elution solutions played a critical role in downstream deboro-bromination. The bromination tolerates a broad range of functional groups, labeling molecules with ranging electronic and steric effects. Bologically active radiopharmaceuticals were synthesized, including two radiobrominated inhibitors of poly ADP ribose polymerase, a clinically relevant chemotherapeutic target for ovarian, breast, and prostate cancers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF

The Staphylococcus aureus cell wall-anchored adhesin ClfA binds to the very large blood circulating protein, von Willebrand factor (vWF) via vWF-binding protein (vWbp), a secreted protein that does not bind the cell wall covalently. Here we perform force spectroscopy studies on living bacteria to unravel the molecular mechanism of this interaction. We discover that the presence of all three binding partners leads to very high binding forces (2000 pN), largely outperforming other known ternary complexes involving adhesins. Strikingly, our experiments indicate that a direct interaction involving features of the dock, lock and latch mechanism must occur between ClfA and vWF to sustain the extreme tensile strength of the ternary complex. Our results support a previously undescribed mechanism whereby vWbp activates a direct, ultra-strong interaction between ClfA and vWF. This intriguing interaction represents a potential target for therapeutic interventions, including synthetic peptides inhibiting the ultra-strong interactions between ClfA and its ligands.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Secreted Effector Proteins of Poplar Leaf Spot and Stem Canker Pathogen Sphaerulina musiva Manipulate Plant Immunity and Contribute to Virulence in Diverse Ways

We report fungal effectors play critical roles in manipulating plant immune responses and promoting colonization. Sphaerulina musiva is a heterothallic ascomycete fungus that causes Septoria leaf spot and stem canker disease in poplar (Populus spp.) plantations. This disease can result in premature defoliation, branch and stem breakage, increased mortality, and plantation failure. However, little is known about the interaction between S. musiva and poplar. Previous work predicted 142 candidate secreted effector proteins in S. musiva (SmCSEPs), 19 of which were selected for further functional characterization in this study. SmCSEP3 induced plant cell death in Nicotiana benthamiana, while 8 out of 19 tested SmCSEPs suppressed cell death. The signal peptides of these eight SmCSEPs exhibited secretory activity in a yeast signal sequence trap assay. Confocal microscopy revealed that four of these eight SmCSEPs target both the cytoplasm and the nucleus, whereas four predominantly localize to discrete punctate structures. Pathogen challenge assays in N. benthamiana demonstrated that the transient expression of six SmCSEPs promoted Fusarium proliferatum infection. The expression of these six SmCSEP genes were induced during infection. SmCSEP2, SmCSEP13, and SmCSEP25 suppressed chitin-triggered reactive oxygen species burst and callose deposition in N. benthamiana. The candidate secreted effector proteins of S. musiva target multiple compartments in the plant cell and modulate different pattern-triggered immunity pathways.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Transcriptome and secretome profiling of sensory neurons reveals sex differences in pathways relevant to insulin sensing and insulin secretion

Sensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex-biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory–islet crosstalk. However, the molecular underpinnings of these male–female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex-biased insulin sensing- and/or insulin secretion-modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5-12 DRG sensory neurons derived from sexually immature 3-week-old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. Furthermore, the transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex-specific candidate molecules with potential regulatory functions in pancreatic β cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG–islet crosstalk with implications in sensory feedback loops in the regulation of β-cell activity in a sex-biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory–islet axis in the regulation of energy balance in males and females.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Design of a 100 kW Surface Permanent Magnet Machine with Wide Constant Power Speed Ratio for Traction Applications

Surface permanent magnet (SPM) machines are considered to be strong candidates for traction applications due to their high power density and high efficiency. By adopting fractional-slot concentrated windings, SPM machines can achieve a wide constant power speed range. A carbon fiber sleeve is applied to ensure the retainment of the magnets at high speed operating conditions. The purpose of this paper is to present the design of a high speed SPM machine for traction applications with 25 kW/Liter active power density and a wide constant-power speed range that is consistent with guidelines and targets presented in the Electrical and Electronics Technical Team Roadmap published by the US Department of Energy. The predicted electromagnetic performance and structural characteristics are presented based on both analytical and FEA results.

42 ENGINEERING↗
DOE OSTI2024

Progress on Pu-238 production at Idaho National Laboratory from February 2022 to July 2023

Idaho National Laboratory (INL) has continued to qualify irradiation positions in the Advanced Test Reactor (ATR) for Pu-238 production to support NASA deep space missions. Over the past year, INL qualified Np-237 targets for ATR’s North East Flux Trap (NEFT), Inner-A and H positions. Work has begun to requalify the South Flux Trap (SFT) and to qualify the East Flux Trap (EFT) for the ATR GEN I target and is midway through the qualification process. This paper gives an overview of operational and technical activities from February 2022 to July 2023.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2022

Driving Zn-MnO2 grid-scale batteries: A roadmap to cost-effective energy storage

Highlights Zn-MnO 2 batteries promise safe, reliable energy storage, and this roadmap outlines a combination of manufacturing strategies and technical innovations that could make this goal achievable. Approaches such as improved efficiency of manufacturing and increasing active material utilization will be important to getting costs as low as $100/kWh, but key materials innovations that facilitate the full 2-electron capacity utilization of MnO 2 , the use of high energy density 3D electrodes, and the promise of a separator-free battery with greater than 2V potential offer a route to batteries at $50/kWh or less. Abstract Large-scale energy storage is certain to play a significant, enabling role in the evolution of the emerging electrical grid. Battery-based storage, while not a dominant form of storage today, has opportunity to expand its utility through safe, reliable, and cost-effective technologies. Here, secondary Zn–MnO 2 batteries are highlighted as a promising extension of ubiquitous primary alkaline batteries, offering a safe, environmentally friendly chemistry in a scalable and practical energy dense technology. Importantly, there is a very realistic pathway to also making such batteries cost-effective at price points of $50/kWh or lower. By examining manufacturing examples at the Zn–MnO 2 battery manufacturer Urban Electric Power, a roadmap has been created to realize such low-cost systems. By focusing on manufacturing optimization through reduced materials waste, scalable manufacturing, and effective materials selection, costs can be significantly reduced. Ultimately, though, coupling these approaches with emerging research and development advances to enable full capacity active materials utilization and battery voltages greater than 2V are likely needed to drive costs below a target of $50/kWh. Reaching this commercially important goal, especially with a chemistry that is safe, well-known, and reliably effective stands to inject Zn–MnO 2 batteries in the storage landscape at a critical time in energy storage development and deployment. Graphical abstract

Spoerke, Erik D. (ORCID:0000000322862560)↗
DOE OSTI2020

Developing an Active Learning algorithm for learning Bayesian classifiers under the Multiple Instance Learning scenario

In the Multiple Instance Learning scenario, the training data consists of instances grouped into bags, and each bag is labelled with whether it is positive, i.e. contains at least one positive instance. First, Active Learning, in which additional labels can be iteratively requested, has the potential to allow more accurate classifiers to be learned with less labels. Active Learning has been applied to the Multiple Instance Learning under two settings: when bag labels of unlabelled bags can be requested, and when instance labels within bags known to be positive can be requested. Second, Bayesian Active learning methods have the potential to learn accurate classifiers with few labels, because they explicitly track the classifier uncertainty and can thus address its knowledge gaps. Yet, there does not exist any Bayesian Active Learning method for the Multiple Instance Learning Scenario. In this work, we develop the first such method. We develop a Bayesian classifier for the Multiple Instance Learning scenario, show how it can be efficiently used for Bayesian Active Learning, and perform experiments assessing its performance. While its performance exceeds that when no Active Learning is used, it is sometimes better, sometimes worse than the naive baseline of uncertainty sampling, depending on the situation. This suggests future work: building more customizable Bayesian Active Learning methods for the Multiple Instance Scenario, customizable to whether bag or instance label accuracy is targeted, and the labeling budget.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2024

Titanium-Cerium Electrode-Decoupled Redox Flow Batteries Integrated With Fossil Fuel Assets For Load-Following, Long-Duration Energy Storage

Operation of fossil plants at partial capacity with frequent cycling results in decreased efficiency, increased emissions and increased wear and maintenance. The objective of this project is to advance the integration of a titanium-cerium electrode-decoupled redox flow battery (RFB) system with conventional fossil-fueled power plants through technical and economic system-level studies and component scale-up and R&D. The Ti-Ce chemistry has a pathway to meet the DOE cost targets of $\$$100/kWh and $\$$0.05/kWh-cycle owing to the use of low-cost, earth abundant elemental actives and incorporation of inexpensive carbon felt electrodes and non-fluorinated anion exchange membrane (AEM) separators. The initial unit cell design was scaled up, with some modifications made to improve ease of manufacturing, from 25 cm 2 cell area to 400 cm 2 . Electrochemical tests demonstrated operation at a current density up to 50 mA/cm 2 , which is on par with other commercial RFB offerings. Furthermore, the Ti-Ce technology developed by WashU was evaluated and tested by industrial team partner, Giner, Inc., in their modular 3-cell stack. Several cell design modifications and alternate component material selections were successfully implemented to accommodate this chemistry while reducing polarization and leakage. Results from stack testing show high columbic efficiency and indicate that further optimization of cell compression and components will lead to successful operation of the Ti-Ce ED-RFB over longer duration at the multi-cell stack level. Engineering and cost analysis showed that an RFB system with power output on the order of 100 MW and with a charge/discharge duration of approx. 12 hours is the most cost effective for integration with fossil plants. At this scale, projected cycling of fossil fuel power plants can be significantly reduced. The use of a storage system is shown to reduce the fossil plant standalone cost of electricity by $\$$7/MWh, through increased capacity factor and improved average efficiency, in the scenario of high penetration of renewable power.

20 FOSSIL-FUELED POWER PLANTS↗
DOE OSTI2026

Williston basin associated co 2 storage field laboratory

The Williston Basin Associated CO 2 Storage Field Laboratory (WBCFL), led by the Energy & Environmental Research Center (EERC) in partnership with Denbury (now ExxonMobil), was established to advance understanding of CO 2 enhanced oil recovery (EOR) and associated geologic CO 2 storage in the Williston Basin. The specific objective of the WBCFL was to conduct field and laboratory activities to inform decisionmakers regarding the 1) efficacy of associated storage in stacked geologic reservoirs during EOR operations; 2) CO 2 injectivity, oil production, and storage in residual oil zones (ROZs); 3) use of a novel CO 2 storage monitoring, verification, and accounting (MVA) technology (active seismoelectric [ASE] monitoring), and 4) life cycle and techno-economic factors for EOR development scenarios targeting ROZs. The project location was the Pennel Field in southeast Montana, which is part of the Cedar Creek Anticline (CCA) geologic structure within the Williston Basin.

02 PETROLEUM↗
DOE OSTI2021

Particle Matter Index and Fuel Wall-wetting Relations on Stochastic Pre-ignition

This works explores the effect of the particle matter index (PMI) and aromatic content on fuel wall impingement and associated stochastic pre-ignition (SPI) propensity. Statically significant measurements of SPI rates are directly coupled with laser induced florescence (LIF) measurements of fuel dilution from spray-linear impingement. Literature suggests that PMI is could be correlated with the number of SPI events, but the root cause(s) of PMI and SPI are directly causational or are a predicator of SPI. Three fuels have been used in this study with 3 different PMI and two different aromatic contents. These fuels are direct injected at two different injection timings, an earlier injection timing which targets the piston crown, 310°CA bTDC, and a later injection timing that the linear, 220°CA bTDC start of injection timings (SOI) respectively. The earlier 310 SOI injection increases soot, whereas the later 220°CD SOI targets the linear and increases wall-wetting. The findings of this work highlight that the SPI activity has a weak correlation with the soot promoted by the combustion process and increased PMI. However, SPI activity shows a strong dependency with high levels of oil dilution and aromatic content, suggesting that PMI might be an indicator of fuel chemistry conducive to SPI and the soot form increased PMI fuels is not a strong source of SPI relative to fuel wall wetting.

42 ENGINEERING↗
DOE OSTI2020

Classification of Dissolution Events Using Fusion of Effluents Measurements and Classifiers

Classifiers for dissolution events at a radiochemical processing facility are studied using gamma spectra measurements of effluents collected by a high purity germanium detector located at its off-gas stack. Data sets collected at the Oak Ridge National Laboratory’s Radiochemical Engineering Development Center under a Pu dissolution campaign spanning a three months period are utilized. Features corresponding to the activity levels of 15 radionuclides, including isotopes of iodine, krypton, and xenon, that are indicated by the target decay chains, are computed from the spectra at 1 hour intervals. A conceptualization diagram is developed to reflect the steps from the source to measurement to feature computation that depend on fission products indicated by decay chains, chemical processing, and effluents transport to the off-gas stack. A diverse set of eight classifiers based on different design principles are trained using the ground truth data for this campaign, and the outputs of top three classifiers, namely, classification trees, Ensemble of Trees (EOT), and k-nearest neighbor, are combined using EOT classifier-fuser. Our results show that for 5-fold cross validation, features associated with isotopes of xenon provide the lowest classification error among the different elements across the classifiers; the classification error is furthered improved when all 15 isotope features are used by each classifier, and it is again improved by the fusion of three classifiers. Further reduction in classification error is achieved by using a measurement window of 1-2 days which is identified based on half-life time estimates of the isotopes; it is long enough for the stabilization of feature estimates while being short enough not to be affected by the follow on dissolution events. As a net result of feature and classifier fusion, combined with the incorporation of decay chain and isotope half-life information, this approach achieves 98% detection rate while maintaining a false alarm rate under 2% for this data set.

Rao, Nageswara↗
DOE OSTI2023

Progress on Pu-238 Production at Idaho National Laboratory From February 2022 to December 2022

Idaho National Laboratory (INL) has continued to qualify irradiation positions in the Advanced Test Reactor (ATR) for Pu-238 production to support NASA deep space missions. Over the past year, INL qualified Np-237 targets for ATR’s North East Flux Trap (NEFT), inner A, and H positions. Work has begun to requalify the South Flux Trap (SFT) and qualify the East Flux Trap (EFT) for the ATR GEN I target and is midway through the qualification process. This paper gives an overview of operational and technical activities from February 2022 to December 2022.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Progress on Pu-238 Production at INL From February 2022 to December 2022

Idaho National Laboratory (INL) has continued to qualify irradiation positions in the Advanced Test Reactor (ATR) for Pu-238 production to support NASA deep space missions. Over the past year, INL qualified Np-237 targets for ATR’s North East Flux Trap (NEFT), inner A, and H positions. Work has begun to requalify the South Flux Trap (SFT) and qualify the East Flux Trap (EFT) for the ATR GEN I target and is midway through the qualification process. This paper gives an overview of operational and technical activities from February 2022 to December 2022.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein

Ligand-binding promiscuity in detoxification systems protects the body from toxicological harm but is a roadblock to drug development due to the difficulty in optimizing small molecules to both retain target potency and avoid metabolic events. Immense effort is invested in evaluating metabolism of molecules to develop safer, more effective treatments, but engineering specificity into or out of promiscuous proteins and their ligands is a challenging task. To better understand the promiscuous nature of detoxification networks, we have used X-ray crystallography to characterize a structural feature of pregnane X receptor (PXR), a nuclear receptor that is activated by diverse molecules (with different structures and sizes) to up-regulate transcription of drug metabolism genes. We found that large ligands expand PXR’s ligand-binding pocket, and the ligand-induced expansion occurs through a specific unfavorable compound-protein clash that likely contributes to reduced binding affinity. Removing the clash by compound modification resulted in more favorable binding modes with significantly enhanced binding affinity. We then engineered the unfavorable ligand-protein clash into a potent, small PXR ligand, resulting in marked reduction in PXR binding and activation. Structural analysis showed that PXR is remodeled, and the modified ligands reposition in the binding pocket to avoid clashes, but the conformational changes result in less favorable binding modes. Thus, ligand-induced binding pocket expansion increases ligand-binding potential of PXR but is an unfavorable event; therefore, drug candidates can be engineered to expand PXR’s ligand-binding pocket and reduce their safety liability due to PXR binding.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Prediction of O and OH Adsorption on Transition Metal Oxide Surfaces from Bulk Descriptors

In the search for stable and active catalysts, density functional theory and machine learning (ML) based models can accelerate the screening of materials. While stability is conveniently addressed on the bulk level of computation, the modelling of catalytic activity requires expensive surface simulations. Here, in this work, we develop models for the surface adsorption energy of O and OH intermediates across a consistent and extensive dataset of pure transition metal oxide surfaces. We show that adsorption energies across metal oxidation states of +2 to +6 are well captured from the metal-oxygen bond strength extracted from the bulk level calculation. Specifically, we calculate the integrated crystal orbital Hamiltonian population (ICOHP) of the metal-oxygen bond in the bulk oxide and employ a simple normalization scheme to obtain a strong correlation with adsorption energetics. By combining our ICOHP descriptor with non DFT features in a Gaussian Process regression (GPR) model, we achieve high model accuracy with mean absolute errors of 0.166 and 0.219 eV for OH and O adsorption, respectively. By targeting the O-OH adsorption energy difference with our GPR model, we predict the the oxygen evolution reaction (OER) activity from bulk descriptors only. Furthermore, we utilize the strong correlation between the COHP and metal oxygen bond lengths to rapidly predict adsorption energetics and catalytic activity from the optimized bulk geometry. Our approach can enable an efficient search for active catalysts by eliminating the need for surface calculations in the initial screening phase.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗