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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 OSTI2024

AMIA KDDM Working Group Collaborative Workshop: Enriching Electronic Health Records with Social Determinants of Health to Improve Outcomes and Health Equity

Prior research has demonstrated that social determinants of health (SDoH) are major drivers of health outcomes and contributors to widespread health inequities. It was estimated that, in the United States, SDoH could be responsible for up to 40% of all preventable deaths, significantly higher than the 10-15% for which better medical care is responsible. Public health interventions that target SDoH are instrumental for improving health outcomes and reducing long-standing health inequities. Currently, most mainstream EHR vendors have implemented SDoH screeners in their EHR systems. However, the utility of the screeners is low, rendering patient-level SDoH still widely unavailable in the structured fields. SDoH are sometimes mentioned in free-text clinical notes (e.g., social context section) where natural language processing (NLP) can be applied to extract relevant information. Contextual-level SDoH can be identified from multiple data sources, many of which are publicly available and spatiotemporally linked to EHR data. As such, there is an opportunity for the KDDM research community to create innovative solutions to draw meaningful insights by creating and using rich data with SDoH to improve health outcomes while reducing disparities. In this workshop organized by AMIA Knowledge Discovery and Data Mining Working Group (AMIA KDDM WG), we will invite world-leading experts from academia, national laboratories, and life science industry with varied backgrounds in biomedical informatics, epidemiology, data science, machine learning, natural language processing, and pediatric cardiology to discuss the best practice of capturing, standardizing, and using SDoH information in various applications aiming at improving outcomes and health equity.

He, Zhe↗
DOE OSTI2024

Methods for ultraviolet excitation microscopy of biological surfaces

Microscopy with Ultraviolet Surface Excitation (MUSE) for use in the classroom to enhance life sciences education and curricula, or for other applications, including without limtiation the operating room, other medical environments, research environments, and low resource environments. MUSE's suitability is based on multiple key factors including its simplicity of use, the incorporation of inexpensive hardware including LED illumination, and very basic tissue preparation. The ultraviolet excitation acts as passive optical sectioning confining the generated fluorescence signal to only a few micrometers below the tissue surface thus eliminating the out of focus signals. This facilitates image capture of tissue microstructure and organization from specimens at the intact or sliced surface arising from varying fluorophore concentration within the different cellular compartments. Although just the tissue auto fluorescence maybe used, image quality is enhanced with brief application of nontoxic fluorescent dyes to selectively highlight cellular compartments. Sample preparation is safe, efficient and familiar to students with basic chemistry or biology lab experience. Mixed-dye powders may be used to simplify translation of this method for educational, medical, research, low resource, and other settings.

Demos, Stavros G.↗
DOE OSTI2020

Challenges and physiological implications of wood feeding in termites

Termites are fascinating insects for a number of reasons, one of which being their specialization on diets of wood lignocellulose. The goal of this review is to consider stress-inducing characteristics of wood and apparent molecular-physiological adaptations in termite guts to overcome these stressors. Defensive factors present in wood include extractive secondary plant metabolites, lignin and related phenolics, crystalline cellulose, and low nitrogen content. Molecular-physiological adaptations of the termite gut to deal with these factors include robust detoxification and antioxidant machinery, the production of a peritrophic matrix and a wide range of cellulases from host and symbiotic sources, and creation of niches available to nitrogen-fixing bacterial symbionts. Considering termite gut physiology and symbioses in the context of stress-response has applied implications. Overall, these outcomes can include development of efficient biomass breakdown strategies, protection of microbes during industrial processing applications, and safeguarding wooden structures from termite damage.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Stress-Induced Changes in Alternative Splicing Landscape in Rice: Functional Significance of Splice Isoforms in Stress Tolerance

Improvements in yield and quality of rice are crucial for global food security. However, global rice production is substantially hindered by various biotic and abiotic stresses. Making further improvements in rice yield is a major challenge to the rice research community, which can be accomplished through developing abiotic stress-resilient rice varieties and engineering durable agrochemical-independent pathogen resistance in high-yielding elite rice varieties. This, in turn, needs increased understanding of the mechanisms by which stresses affect rice growth and development. Alternative splicing (AS), a post-transcriptional gene regulatory mechanism, allows rapid changes in the transcriptome and can generate novel regulatory mechanisms to confer plasticity to plant growth and development. Mounting evidence indicates that AS has a prominent role in regulating rice growth and development under stress conditions. Several regulatory and structural genes and splicing factors of rice undergo different types of stress-induced AS events, and the functional significance of some of them in stress tolerance has been defined. Both rice and its pathogens use this complex regulatory mechanism to devise strategies against each other. This review covers the current understanding and evidence for the involvement of AS in biotic and abiotic stress-responsive genes, and its relevance to rice growth and development. Furthermore, we discuss implications of AS for the virulence of different rice pathogens and highlight the areas of further research and potential future avenues to develop climate-smart and disease-resistant rice varieties.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Free Energy and Flexibility Analysis of Autoinhibited Human BRAF

The RAF serine/threonine protein kinases function as direct effectors of RAS in the intracellular transmission of extracellular growth signals, and they are key targets for drug discovery, given the high incidence of oncogenic mutations in RAF and other components of this signaling pathway. In its inactive state, RAF is held in an autoinhibited conformation in the cytosol through a combination of intramolecular interactions and binding to a regulatory 14−3−3 protein dimer. Activation of RAF is initiated by its interaction with membrane-localized GTP-bound RAS, which induces conformational changes that release RAF from its autoinhibited state. However, the molecular mechanisms governing RAF activation remain incomplete, largely due to the challenges in experimentally capturing the intermediate conformational states in this process. To address this gap, we developed a comprehensive all-atom model of BRAF based on existing cryo-EM structures. Using this model, we performed extensive molecular dynamics simulations to evaluate the stability and free energy landscape of autoinhibited BRAF in solution. Our analysis reveals conformational flexibility within the autoinhibited complex, suggesting that this dynamic behavior may play a role in facilitating BRAF activation upon engagement with the membrane-bound RAS.

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

n-Butanol production by Rhodopseudomonas palustris TIE-1

Anthropogenic carbon dioxide (CO 2 ) release in the atmosphere from fossil fuel combustion has inspired scientists to study CO 2 to biofuel conversion. Oxygenic phototrophs such as cyanobacteria have been used to produce biofuels using CO 2 . However, oxygen generation during oxygenic photosynthesis adversely affects biofuel production efficiency. To produce n-butanol (biofuel) from CO 2 , here we introduce an n-butanol biosynthesis pathway into an anoxygenic (non-oxygen evolving) photoautotroph, Rhodopseudomonas palustris TIE-1 (TIE-1). Using different carbon, nitrogen, and electron sources, we achieve n-butanol production in wild-type TIE-1 and mutants lacking electron-consuming (nitrogen-fixing) or acetyl-CoA-consuming (polyhydroxybutyrate and glycogen synthesis) pathways. The mutant lacking the nitrogen-fixing pathway produce the highest n-butanol. Coupled with novel hybrid bioelectrochemical platforms, this mutant produces n-butanol using CO 2 , solar panel-generated electricity, and light with high electrical energy conversion efficiency. Overall, this approach showcases TIE-1 as an attractive microbial chassis for carbon-neutral n-butanol bioproduction using sustainable, renewable, and abundant resources.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Effects of presenilin-1 familial Alzheimer’s disease mutations on γ-secretase activation for cleavage of amyloid precursor protein

Presenilin-1 (PS1) is the catalytic subunit of γ-secretase which cleaves within the transmembrane domain of over 150 peptide substrates. Dominant missense mutations in PS1 cause early-onset familial Alzheimer’s disease (FAD); however, the exact pathogenic mechanism remains unknown. Here we combined Gaussian accelerated molecular dynamics (GaMD) simulations and biochemical experiments to determine the effects of six representative PS1 FAD mutations (P117L, I143T, L166P, G384A, L435F, and L286V) on the enzyme-substrate interactions between γ-secretase and amyloid precursor protein (APP). Biochemical experiments showed that all six PS1 FAD mutations rendered γ-secretase less active for the endoproteolytic (ε) cleavage of APP. Distinct low-energy conformational states were identified from the free energy profiles of wildtype and PS1 FAD-mutant γ-secretase. The P117L and L286V FAD mutants could still sample the “Active” state for substrate cleavage, but with noticeably reduced conformational space compared with the wildtype. The other mutants hardly visited the “Active” state. The PS1 FAD mutants were found to reduce γ-secretase proteolytic activity by hindering APP residue L49 from proper orientation in the active site and/or disrupting the distance between the catalytic aspartates. Therefore, our findings provide mechanistic insights into how PS1 FAD mutations affect structural dynamics and enzyme-substrate interactions of γ-secretase and APP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Investigation of the 244 Pu ⁢( 48 Ca,𝑥⁢𝑛) 292−𝑥 Fl reaction with the LBNL SHREC detector: Investigation of decay chains of isotopes of flerovium (𝑍=114)

The 244 Pu ⁢( 48 Ca,𝑥⁢𝑛)⁢ 292−𝑥 Fl reaction was investigated at Lawrence Berkeley National Laboratory’s 88 Inch Cyclotron using the Berkeley Gas-filled Separator (BGS), the newly installed Superheavy Recoil detector, along with an upgraded digital electronics and data acquisition system. Seven decay chains were observed starting with an evaporation residue, followed by a single 𝛼 decay and a spontaneous fission. The decay characteristics of these seven decay chains led to an assignment to 288 Fl , the product of the 4⁢𝑛 reaction channel. Two additional chains were (tentatively) assigned to the decay of the 3⁢𝑛 exit channel, 289 Fl . Cross sections for the 4⁢𝑛 and 3⁢𝑛 exit channels were 𝜎 prod =6.7⁢($^{36}_{25}$) pb and 𝜎 prod =1.6⁢($^{22}_{11}$) pb, respectively. Another decay chain, tentatively assigned to the 5⁢𝑛 exit channel through the 48 Ca + 244 Pu reaction or the 3⁢𝑛 exit channel of the 48 Ca + 242 Pu reaction, was also detected. Detailed information regarding the observed decay chains and their nuclear structure aspects is discussed, along with the performance of the BGS and the new detection system.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2023

Structural and functional insights into δ-poly-L-ornithine polymer biosynthesis from Acinetobacter baumannii

Cationic homo-polyamino acid (CHPA) peptides containing isopeptide bonds of diamino acids have been identified from Actinomycetes strains. However, none has been reported from other bacteria. Here, we report a δ-poly-L-ornithine synthetase from Acinetobacter baumannii, which we name PosA. Surprisingly, structural analysis of the adenylation domain and biochemical assay shows L-ornithine as the substrate for PosA. The product from the enzymatic reaction was purified and identified as poly-L-ornithine composed of 7-12 amino acid units. Chemical labeling of the polymer confirmed the isopeptide linkage of δ-poly-L-ornithine. We examine the biological activity of chemically synthesized 12-mer δ-poly-L-ornithine, illustrating that the polymer may act as an anti-fungal agent. Structures of the isolated adenylation domain from PosA are presented with several diamino acids and biochemical assays identify important substrate binding residues. Structurally-guided genome-mining led to the identification of homologs with different substrate binding residues that could activate additional substrates. A homolog from Bdellovibrionales sp. shows modest activity with L-arginine but not with any diamino acids observed to be substrates for previously examined CHPA synthetases. Our study indicates the possibility that additional CHPAs may be produced by various microbes, supporting the further exploration of uncharacterized natural products.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Conformational heterogeneity of the BTK PHTH domain drives multiple regulatory states

Full-length Bruton’s tyrosine kinase (BTK) has been refractory to structural analysis. The nearest full-length structure of BTK to date consists of the autoinhibited SH3–SH2–kinase core. Precisely how the BTK N-terminal domains (the Pleckstrin homology/Tec homology [PHTH] domain and proline-rich regions [PRR] contain linker) contribute to BTK regulation remains unclear. We have produced crystals of full-length BTK for the first time but despite efforts to stabilize the autoinhibited state, the diffraction data still reveal only the SH3–SH2–kinase core with no electron density visible for the PHTH–PRR segment. Cryo-electron microscopy (cryoEM) data of full-length BTK, on the other hand, provide the first view of the PHTH domain within full-length BTK. CryoEM reconstructions support conformational heterogeneity in the PHTH–PRR region wherein the globular PHTH domain adopts a range of states arrayed around the autoinhibited SH3–SH2–kinase core. On the way to activation, disassembly of the SH3–SH2–kinase core opens a new autoinhibitory site on the kinase domain for PHTH domain binding that is ultimately released upon interaction of PHTH with phosphatidylinositol (3,4,5)-trisphosphate. Membrane-induced dimerization activates BTK and we present here a crystal structure of an activation loop swapped BTK kinase domain dimer that likely represents the conformational state leading to trans-autophosphorylation. Together, these data provide the first structural elucidation of full-length BTK and allow a deeper understanding of allosteric control over the BTK kinase domain during distinct stages of activation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Heparan sulfate promotes TRAIL-induced tumor cell apoptosis

TRAIL (TNF-related apoptosis-inducing ligand) is a potent inducer of tumor cell apoptosis through TRAIL receptors. While it has been previously pursued as a potential anti-tumor therapy, the enthusiasm subsided due to unsuccessful clinical trials and the fact that many tumors are resistant to TRAIL. In this report, we identified heparan sulfate (HS) as an important regulator of TRAIL-induced apoptosis. TRAIL binds HS with high affinity (K D = 73 nM) and HS induces TRAIL to form higher-order oligomers. The HS-binding site of TRAIL is located at the N-terminus of soluble TRAIL, which includes three basic residues. Binding to cell surface HS plays an essential role in promoting the apoptotic activity of TRAIL in both breast cancer and myeloma cells, and this promoting effect can be blocked by heparin, which is commonly administered to cancer patients. We also quantified HS content in several lines of myeloma cells and found that the cell line showing the most resistance to TRAIL has the least expression of HS, which suggests that HS expression in tumor cells could play a role in regulating sensitivity towards TRAIL. We also discovered that death receptor 5 (DR5), TRAIL, and HS can form a ternary complex and that cell surface HS plays an active role in promoting TRAIL-induced cellular internalization of DR5. Combined, our study suggests that TRAIL-HS interactions could play multiple roles in regulating the apoptotic potency of TRAIL and might be an important point of consideration when designing future TRAIL-based anti-tumor therapy.

60 APPLIED LIFE SCIENCES↗