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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 523 records · Page 29
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Open Source Scalable Data Services and Data Fusion for Biological and Environmental Sciences (SBIR Phase I Final Scientific/ Technical Report)

The overarching goal of the project is to develop an integrated open-source scientific data management system (Apache V2 license), ResonantEco, that meets the need of biological and environmental researchers and developers for data management, curation, and data processing for analyses with a wide range of scale and complexity. ResonantEco will provide web enabled data services with features such as unified data interfaces and federated views of data and metadata for heterogeneous data sources with an interactive web client for data exploration. Our use of the term fusion is taken from geospatial (GIS) domain where data fusion is often synonymous with data integration. In particular, data integration in ResonantEco involves combining data residing in different sources and providing users with a unified view of them.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Neutrons in Structural Biology: Challenges and Opportunities (Workshop Report)

Gaining a thorough understanding of biological systems requires building our knowledge about biological processes from the level of atoms and electrons, and up to whole organisms. Such comprehensive knowledge will allow for a predictive understanding of complex biological systems behavior. It will guide us in the design and development of novel therapeutics and vaccines to tackle existing health threats and to prepare for future pandemics, and it will provide information necessary to create new biomaterials and bio-inspired technologies through manipulation of biological macromolecules, their assemblies, single cells and even microorganisms. Reaching these goals will require a synergistic combination of multiple experimental techniques with molecular calculations and predictive simulations, and the design and development of new techniques and capabilities that bridge current knowledge and technology gaps. Neutron scattering provides unique information about the biomacromolecular structure and function and can play a major role in achieving these goals. A workshop was held to engage the scientific community in identifying pressing challenges in biochemistry, structural biology, enzymology and structure-guided drug design not solved with the current neutron scattering technologies or utilizing other structural biology techniques such as X-ray crystallography, NMR, and cryo-EM. The workshop brought together structural biology, biochemistry and computational experts, as well as early career researchers and students, creating a forum for discussing scientific advancement and collaboration. The workshop included a one-day satellite training workshop where graduate students and postdoctoral researchers were educated in the application of neutron crystallography and small-angle scattering in structural biology. Furthermore, the Instrument Scientific Advisory Board (ISAB) for the development of a macromolecular neutron diffractometer at ORNL’s Second Target Station was introduced at the workshop. The major outcome was that neutrons can provide atomic-level understanding of biomacromolecular structure, function and dynamics which is of paramount importance for addressing the identified challenges. Neutron crystallography, in particular, can resolve long-standing biochemical issues regarding enzyme function by delineating the underlying chemistry and can have a major impact on the design of small-molecule therapeutics, especially in combination with molecular computation (quantum chemistry and molecular dynamics simulations) and the emerging artificial intelligence (AI)-assisted drug design technologies. The unique properties of neutrons, including their high sensitivity to hydrogen and their non-destructive nature, make them ideal probes of biological matter. There is a palpable need in the scientific community to expand and enhance the impact of neutron sciences on biology. Neutron crystallography is the only structural biology method capable of determining positions of all hydrogen atoms in proteins, nucleic acids and their complexes at near-physiological temperatures and of unstable species at cryogenic temperatures. Moreover, neutron analysis is non-ionizing, non-destructive and does not perturb the structure or redox chemistry of active site metal centers and clusters in proteins, which can be invaluable for studying radiation-sensitive metalloprotein complexes. Further, neutron energies used in scattering applications are similar to atomic motions, permitting neutron spectroscopies to characterize the dynamics of biomacromolecules on the picosecond to microsecond timescales. The different sensitivities of neutrons to protium (H) and deuterium (D) isotopes of hydrogen allow enhanced visibility of specific parts of biological complexes through isotopic labeling. The impact of neutrons will be most powerful when neutron scattering is combined with complementary experimental techniques that use photons and electrons, and with high-performance computing. The interconnection and mutuality of the experimental and theoretical capabilities will drive discoveries in biological and health sciences to generate more complete picture of complex biological systems. The major limitation in the field of biological neutron crystallography has been signal-to-noise, demanding large samples that are difficult to produce for the majority of biomacromolecules and limiting the applicability of this technique in biological sciences. A neutron crystallography instrument at the Second Target Station will revolutionize biological science with neutrons by engaging a large scientific community of structural biologists, enabling successful neutron diffraction experiments from radically smaller biomacromolecular crystals, resolving unanswered biochemical questions, and meaningfully contributing to rational drug design. The meeting highlighted 10 grand challenges that will be addressed with this advanced capability over the next decade and beyond, and the recommendations required to help address them are given below.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

The Integration of Life Sciences in Space: Astrobiology and Space Biology Virtual Workshops Report

A series of virtual workshops was held during June 2020 to seek ways to integrate the efforts of the astrobiology and space biology research communities under a broad umbrella of space life sciences. The overall goal was to help inspire creativity that will guide us towards new synergistic ideas complementing these existing disciplines that are of such importance to NASA. Workshop participants aspired to: (1) Exploit synergies across the biological sciences at NASA, (2) Foster research, enabling technology, and mission concepts that support commonalities in space biology, astrobiology, synthetic biology, planetary protection, and relevant human health, performance, and habitation concerns, (3) Envision the development of an “Arc of Biology in Space” to encompass this multi-faceted joint research community. The focused objective of the workshop series was to explore and demonstrate how the integration of astrobiology and space biology could be achieved, identify strengths and weaknesses in the current state of the art, and recognize where our greatest challenges lay. Specifically, we seek to: (1) Establish a scientific framework for an integrated life sciences effort, (2) Pioneer discovery by creating unique opportunities in the fundamental biological sciences, (3) Explore novel combinations of existing technologies across the relevant disciplines, (4) Invent new technologies and applications in space life sciences, and (5) Creatively increase access to spaceflight, emerging and novel technologies, Earth analogs, and simulated natural and spaceflight environments. The community aims for a broad arc of biological competence in the context of space and planetary science, spaceflight, and habitation. We will present dominant themes and innovative ideas that resulted from this interchange of relevant communities.

astrobiology↗
NASA NTRS2020

The Integration of Life Sciences in Space: Astrobiology and Space Biology Virtual Workshops Report

A series of virtual workshops was held during June 2020 to seek ways to integrate the efforts of the astrobiology and space biology research communities under a broad umbrella of space life sciences. The overall goal was to help inspire creativity that will guide us towards new synergistic ideas complementing these existing disciplines that are of such importance to NASA. Workshop participants aspired to: (1) Exploit synergies across the biological sciences at NASA, (2) Foster research, enabling technology, and mission concepts that support commonalities in space biology, astrobiology, synthetic biology, planetary protection, and relevant human health, performance, and habitation concerns, (3) Envision the development of an “Arc of Biology in Space” to encompass this multi-faceted joint research community. The focused objective of the workshop series was to explore and demonstrate how the integration of astrobiology and space biology could be achieved, identify strengths and weaknesses in the current state of the art, and recognize where our greatest challenges lay. Specifically, we seek to: (1) Establish a scientific framework for an integrated life sciences effort, (2) Pioneer discovery by creating unique opportunities in the fundamental biological sciences, (3) Explore novel combinations of existing technologies across the relevant disciplines, (4) Invent new technologies and applications in space life sciences, and (5) Creatively increase access to spaceflight, emerging and novel technologies, Earth analogs, and simulated natural and spaceflight environments. The community aims for a broad arc of biological competence in the context of space and planetary science, spaceflight, and habitation. We will present dominant themes and innovative ideas that resulted from this interchange of relevant communities.

astrobiology↗
DOE OSTI2023

Prolonging genetic circuit stability through adaptive evolution of overlapping genes

Abstract The development of synthetic biological circuits that maintain functionality over application-relevant time scales remains a significant challenge. Here, we employed synthetic overlapping sequences in which one gene is encoded or ‘entangled’ entirely within an alternative reading frame of another gene. In this design, the toxin-encoding relE was entangled within ilvA, which encodes threonine deaminase, an enzyme essential for isoleucine biosynthesis. A functional entanglement construct was obtained upon modification of the ribosome-binding site of the internal relE gene. Using this optimized design, we found that the selection pressure to maintain functional IlvA stabilized the production of burdensome RelE for >130 generations, which compares favorably with the most stable kill-switch circuits developed to date. This stabilizing effect was achieved through a complete alteration of the allowable landscape of mutations such that mutations inactivating the entangled genes were disfavored. Instead, the majority of lineages accumulated mutations within the regulatory region of ilvA. By reducing baseline relE expression, these more ‘benign’ mutations lowered circuit burden, which suppressed the accumulation of relE-inactivating mutations, thereby prolonging kill-switch function. Overall, this work demonstrates the utility of sequence entanglement paired with an adaptive laboratory evolution campaign to increase the evolutionary stability of burdensome synthetic circuits.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Information-incorporated gene network construction with FDR control

Abstract Motivation Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. Results In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. Availability and implementation R package is freely available for download at https://cran.r-project.org/package=PCGII.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

AI-accelerated protein-ligand docking for SARS-CoV-2 is 100-fold faster with no significant change in detection

Protein-ligand docking is a computational method for identifying drug leads. The method is capable of narrowing a vast library of compounds down to a tractable size for downstream simulation or experimental testing and is widely used in drug discovery. While there has been progress in accelerating scoring of compounds with artificial intelligence, few works have bridged these successes back to the virtual screening community in terms of utility and forward-looking development. We demonstrate the power of high-speed ML models by scoring 1 billion molecules in under a day (50 k predictions per GPU seconds). We showcase a workflow for docking utilizing surrogate AI-based models as a pre-filter to a standard docking workflow. Our workflow is ten times faster at screening a library of compounds than the standard technique, with an error rate less than 0.01% of detecting the underlying best scoring 0.1% of compounds. Our analysis of the speedup explains that another order of magnitude speedup must come from model accuracy rather than computing speed. In order to drive another order of magnitude of acceleration, we share a benchmark dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million “in-stock” molecules over 15 receptors, or binding sites, across the SARS-CoV-2 proteome. We believe this is strong evidence for the community to begin focusing on improving the accuracy of surrogate models to improve the ability to screen massive compound libraries 100 × or even 1000 × faster than current techniques and reduce missing top hits. The technique outlined aims to be a fast drop-in replacement for docking for screening billion-scale molecular libraries.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Plants use molecular mechanisms mediated by biomolecular condensates to integrate environmental cues with development

This review highlights recent literature on biomolecular condensates in plant development and discusses challenges for fully dissecting their functional roles. Plant developmental biology has been inundated with descriptive examples of biomolecular condensate formation, but it is only recently that mechanistic understanding has been forthcoming. Here, we discuss recent examples of potential roles biomolecular condensates play at different stages of the plant life cycle. We group these examples based on putative molecular functions, including sequestering interacting components, enhancing dwell time, and interacting with cytoplasmic biophysical properties in response to environmental change. We explore how these mechanisms could modulate plant development in response to environmental inputs and discuss challenges and opportunities for further research into deciphering molecular mechanisms to better understand the diverse roles that biomolecular condensates exert on life.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Endogenous Production and Vibrational Analysis of Heavy-Isotope-Labeled Peptides from Cyanobacteria

Stable isotope labeling is an extremely useful tool for characterizing the structure, tracing the metabolism, and imaging the distribution of natural products in living organisms using mass-sensitive measurement techniques. In this study, a cyanobacterium was cultured in 15 N/ 13 C-enriched media to endogenously produce labeled, bioactive oligopeptides. The extent of heavy isotope incorporation in these peptides was determined with LC–MS, while the overall extent of heavy isotope incorporation in whole cells was studied with nanoSIMS and AFM-IR. Up to 98 % heavy isotope incorporation was observed in labeled cells. Three of the most abundant peptides, microcystin-LR (MCLR), cyanopeptolin-A (CYPA), and aerucyclamide-A (ACAA), were isolated and further studied with Raman and FTIR spectroscopies and DFT calculations. This revealed several IR and Raman active vibrations associated with functional groups not common in ribosomal peptides, like diene, ester, thiazole, thiazoline, and oxazoline groups, which could be suitable for future vibrational imaging studies. More broadly, this study outlines a simple and relatively inexpensive method for producing heavy-labeled natural products. Finally, manipulating the bacterial culture conditions by the addition of specific types and amounts of heavy-labeled nutrients provides an efficient means of producing heavy-labeled natural products for mass-sensitive imaging studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Unravelling the hidden power of esterases for biomanufacturing of short-chain esters

Abstract Microbial production of esters has recently garnered wide attention, but the current production metrics are low. Evidently, the ester precursors (organic acids and alcohols) can be accumulated at higher titers by microbes like Escherichia coli . Hence, we hypothesized that their ‘direct esterification’ using esterases will be efficient. We engineered esterases from various microorganisms into E. coli , along with overexpression of ethanol and lactate pathway genes. High cell density fermentation exhibited the strains possessing esterase-A (SSL76) and carbohydrate esterase (SSL74) as the potent candidates. Fed-batch fermentation at pH 7 resulted in 80 mg/L of ethyl acetate and 10 mg/L of ethyl lactate accumulation by SSL76. At pH 6, the total ester titer improved by 2.5-fold, with SSL76 producing 225 mg/L of ethyl acetate, and 18.2 mg/L of ethyl lactate, the highest reported titer in E. coli . To our knowledge, this is the first successful demonstration of short-chain ester production by engineering ‘esterases’ in E. coli .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Evolutionary and functional relationships between plant and microbial C 1 metabolism in terrestrial ecosystems

One-carbon (C 1 ) metabolism, centered on the universal methyl donor S-adenosyl methionine (SAM), plays critical roles in biosynthesis, redox regulation, and stress responses across plants and microbes. A recently proposed photosynthetic C 1 pathway links SAM methyl groups directly to RuBisCO-mediated CO 2 assimilation and integrates with nitrogen and sulfur metabolism. Light-dependent SAM synthesis may regulate the methylation of biopolymers and specialized metabolites and help mitigate photorespiratory stress under elevated temperature and drought. Phylogenetic analysis of two core enzymes suggests evolutionary continuity from methylotrophic microbes to land plants, supporting microbial origins via endosymbiotic gene transfer. Beyond intracellular roles, C 1 metabolism drives biosphere–atmosphere exchange via gases such as methane, methanol, formic acid, and formaldehyde, and numerous specialized volatiles synthesized through SAM methylation. S-methylmethionine, a mobile C 1 metabolite, may mediate phloem transport of reduced sulfur, nitrogen, and methyl groups, linking above- and belowground C 1 cycling in plants. Advances in real-time gas sensing now allow the high-frequency quantification of C 1 fluxes from leaves, stems, and soils, highlighting C 1 metabolism as a critical and underrecognized component of terrestrial carbon and nutrient cycling. Given its microbial ancestry and the production of diverse volatile biosignatures, C 1 metabolism may also offer unique insights into life's origins and biosignature detection on exoplanets.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

CD206 + Trem2 + macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice

Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206 + macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206 + macrophages also robustly expressed Trem2 , a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Swab Tensile Testing Results and Procedures

This tensile test is to mimic the worst-case scenario of the swab being caught on an obstruction when being pulled out of the nasopharyngeal space. It is to determine how much tensile force the swab can withstand without breaking. A variety of different swabs (different materials and different geometries) were tested using the protocol outlined in Section 2 (Tensile Testing Procedure). Not all of the swabs were pre-treated using the Autoclave. For those swabs that were pre-treated using the Autoclave, the tensile tests were performed within 6 hours of completion of the Autoclave pre-treatment, with the exception of the “Aged” swabs. For the “Aged” swabs, the tensile tests were performed 7 days after the Autoclave pre -treatment. All swabs were provided by HP.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Swab Tensile Testing Results [Slides]

HP PA11 material swabs predominantly broke at the joint between the head and the neck, although there was significant variation in the break locations. HP PA12, Injection Molded, and FormLabs (Surgical Guide V1 Resin) material swabs predominately broke in the neck region.

36 MATERIALS SCIENCE↗