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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 1,189 records · Page 66
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Evaluating the Pharmacodynamics and Protective Efficacy of Catalytic Bioscavenger following Subcutaneous Administration in Guinea Pigs

Previous studies determined the guinea pig was a viableanimal model for evaluating subcutaneous ( s.c. )injection as an alternative route of administration of catalytic Bioscavengers:enzymes designed to render nerve agents non‐toxic in systemic circulation following exposure. Recent studies have focused on evaluating the pharmacodynamics (PD) and protective efficacy (PE) of the lead bioscavenger candidate, organophosphorus hydrolase (OPH) variant, YT, as both unmodified and modified (PEGylated) versions of the enzyme. A comparative study was conducted with YT and three progressively sized PEG‐YT variants (934, 935, and 936) following a single bolus s.c. dose (5 mg/kg). Bioavailability increased linearly with molecular size such that the largest sized PEG‐YT variant, 936, afforded the highest bioavailability, thus promoting 936 to subsequent PD and PEstudies. Dose dependence on bioavailability was also examined via three cohorts of guinea pigs receiving doses (5, 15, 20 mg/kg) of either YT or 936 in which a linear dose response was also found. Guinea pigs receiving either YT or 936 (5 mg/kg) via intramuscular (i.m. )or s.c. routes had superimposable PD profiles regardless of route, suggesting an identical absorption pathway for the drugs. Protective efficacy was also evaluated by exposing the animals to 2xLD 50 of sarin (GB) 7 dayspost‐enzyme administration; only the animals receiving 936 ( i.m. and s.c. ) survived 24 hours post‐exposure. Periodic s.c. dosing strategies were also evaluated with 936 in which three injections were administered either 2 or 24 hours apart for a total dose of 15 mg/kg followed by a protective efficacy assessment 8 days post‐administration. Overall these data support the use of s.c . injection as a practical route of administration for catalytic bioscavenger with PE Gylation, synergistically enhancing both bioavailability and extending drug half‐life in circulation. Support or Funding Information The views expressed in this abstract are those of the author(s) and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. The experimental protocol was approved by the Animal Care and Use Committee at the United States Army Medical Research Institute of ChemicalDefense and all procedures were conducted in accordance with the principlesstated in the Guide for the Care and Use of Laboratory Animals and the AnimalWelfare Act of 1966 (P.L. 89–544), as amended. This work was supported by the Defense Threat Reduction Agency‐Joint Science and Technology Office, MedicalS&T Division. *Thisresearch was supported in part by an appointment to the Postgraduate ResearchParticipation Program at the U.S. Army Medical Research Institute of ChemicalDefense administered by the Oak Ridge Institute for Science and Educationthrough an interagency agreement between the U.S. Department of Energy and USAMRMC. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Dao, Thuy↗
NASA NTRS1990

A direct screening procedure for gravitropism mutants in Arabidopsis thaliana (L.) Heynh

In order to isolate gravitropism mutants of Arabidopsis thaliana (L.) Heynh. var Estland for the genetic dissection of the gravitropism pathway, a direct screening procedure has been developed in which mutants are selected on the basis of their gravitropic response. Variability in hypocotyl curvature was dependent on the germination time of each seed stock, resulting in the incorrect identification of several lines as gravitropism mutants when a standard protocol for the potentiation of germination was used. When the protocol was adjusted to allow for differences in germination time, these lines were eliminated from the collection. Out of the 60,000 M2 seedlings screened, 0.3 to 0.4% exhibited altered gravitropism. In approximately 40% of these mutant lines, only gravitropism by the root or the hypocotyl was altered, while the response of the other organ was unaffected. These data support the hypothesis that root and hypocotyl gravitropism are genetically separable.

NASA Discipline Number 29-20↗
DOE OSTI2016

Emissions reduction scenarios in the Argentinean Energy Sector

Here in this paper the LEAP, TIAM-ECN, and GCAM models were applied to evaluate the impact of a variety of climate change control policies (including carbon pricing and emission constraints relative to a base year) on primary energy consumption, final energy consumption, electricity sector development, and CO 2 emission savings of the energy sector in Argentina over the 2010-2050 period. The LEAP model results indicate that if Argentina fully implements the most feasible mitigation measures currently under consideration by official bodies and key academic institutions on energy supply and demand, such as the ProBiomass program, a cumulative incremental economic cost of 22.8 billion US$(2005) to 2050 is expected, resulting in a 16% reduction in GHG emissions compared to a business-as-usual scenario. These measures also bring economic co-benefits, such as a reduction of energy imports improving the balance of trade. A Low CO 2 price scenario in LEAP results in the replacement of coal by nuclear and wind energy in electricity expansion. A High CO 2 price leverages additional investments in hydropower. An emission cap scenario (2050 emissions 20% lower than 2010 emissions) is feasible by including such measures as CCS and Bio CCS, but at a significant cost. By way of cross-model comparison with the TIAM-ECN and GCAM global integrated assessment models, significant variation in projected emissions reductions in the carbon price scenarios was observed, which illustrates the inherent uncertainties associated with such long-term projections. These models predict approximately 37% and 94% reductions under the High CO 2 price scenario, respectively. By comparison, the LEAP model, using an approach based on the assessment of a limited set of mitigation options, predicts a 11.3% reduction under the ‘high’ carbon tax. The main reasons for this difference are differences in assumptions about technology cost and availability, CO 2 storage capacity, and the ability to import bioenergy. In terms of technology pathways, the models agree that fossil fuels, in particular natural gas, will remain an important part of the electricity mix in the core baseline scenario. Finally, according to the models there is agreement that the introduction of a carbon price will lead to a decline in absolute and relative shares of aggregate fossil fuel generation. However, predictions vary as to the extent to which coal, nuclear and renewable energy play a role.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2013

Identification of DSB-1, a Protein Required for Initiation of Meiotic Recombination in Caenorhabditis elegans , Illuminates a Crossover Assurance Checkpoint

Meiotic recombination, an essential aspect of sexual reproduction, is initiated by programmed DNA double-strand breaks (DSBs). DSBs are catalyzed by the widely-conserved Spo11 enzyme; however, the activity of Spo11 is regulated by additional factors that are poorly conserved through evolution. To expand our understanding of meiotic regulation, we have characterized a novel gene, dsb-1, that is specifically required for meiotic DSB formation in the nematode Caenorhabditis elegans. DSB-1 localizes to chromosomes during early meiotic prophase, coincident with the timing of DSB formation. DSB-1 also promotes normal protein levels and chromosome localization of DSB-2, a paralogous protein that plays a related role in initiating recombination. Mutations that disrupt crossover formation result in prolonged DSB-1 association with chromosomes, suggesting that nuclei may remain in a DSB-permissive state. Extended DSB-1 localization is seen even in mutants with defects in early recombination steps, including spo-11, suggesting that the absence of crossover precursors triggers the extension. Strikingly, failure to form a crossover precursor on a single chromosome pair is sufficient to extend the localization of DSB-1 on all chromosomes in the same nucleus. Based on these observations we propose a model for crossover assurance that acts through DSB-1 to maintain a DSB-permissive state until all chromosome pairs acquire crossover precursors. This work identifies a novel component of the DSB machinery in C. elegans, and sheds light on an important pathway that regulates DSB formation for crossover assurance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy

Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallographic interface, and resulted in mutant PD-1 receptors with altered affinity and ligand-specificity. In particular, a high-affinity mutant PD-1 (HA PD-1) exhibited 45 and 30-fold increase in binding to PD-L1 and PD-L2, respectively, due to slower dissociation rates. This mutant (A132L) was used to engineer a soluble chimeric Ig fusion protein for cell-based and in vivo studies. HA PD-1 Ig showed enhanced binding to human dendritic cells, and increased T cell proliferation and cytokine production in a mixed lymphocyte reaction (MLR) assay. Moreover, in an experimental model of murine Lewis lung carcinoma, HA PD-1 Ig treatment synergized with radiation therapy to decrease local and metastatic tumor burden, as well as in the establishment of immunological memory responses. Our studies highlight the value of structural considerations in guiding the design of a high-affinity chimeric PD-1 Ig fusion protein with robust immune modulatory properties, and underscore the power of combination therapies to selectively manipulate the PD-1 pathway for tumor immunotherapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Reaction Rate Theory in Coordination Number Space: An Application to Ion Solvation

Understanding reaction mechanisms in many chemical and biological processes require application of rare event theories. In these theories, an effective choice of a reaction coordinate to describe a reaction pathway is essential. To this end, we study ion solvation in water using molecular dynamics simulations and explore the utility of coordination number (n = number of water molecules in the first solvation shell) as the reaction coordinate. Here we compute the potential of mean force (W(n)) using umbrella sampling, predicting multiple metastable n-states for both cations and anions. We find with increasing ionic size, these states become more stable and structured for cations when compared to anions. We have extended transition state theory (TST) to calculate transition rates between n-states. TST overestimates the rate constant due to solvent-induced barrier recrossings that are not accounted for. We correct the TST rates by calculating transmission coefficients using the reactive flux method. This approach enables a new way of understanding rare events involving coordination complexes. We gratefully acknowledge Liem Dang and Panos Stinis for useful discussion. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. SR, CJM, and GKS were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. MDB was supported by MS3 (Materials Synthesis and Simulation Across Scales) Initiative, a Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory (PNNL). PNNL is a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy.

Roy, Santanu↗
DOE OSTI2016

Stem Inc. SunShot Incubator Program Final Technical Report

In this Energy Storage Control Algorithms project, Stem sought to develop tools and control algorithms to increase the value and reduce balance-of-system and grid integration costs associated with adding distributed solar generation to the grid. These advances fell under the headings SolarScope and SolarController. Stem sought to create initial market traction with a fully commercialized product for the solar industry to size storage systems (SolarScope) as well as a solar intermittency-mitigation framework for utilities (SolarController) in the course of the project. The company sought to align strategic growth plans and enable the rollout of the products to broader audiences in multiple geographic regions by leveraging the major solar companies in the national market as partners. Both final products were both intended to be commercialized. They are: SolarScope: Analysis tool to identify viable PV + storage projects and thereby expedite the sales and interconnection processes. SolarScope combines customer load data, PV production estimates, utility rate tariff, and simulated storage into a simple user interface for PV developers. Developers can easily identify viable solar + storage sites without the need for complex and time consuming, site-by-site spreadsheet modeling. SolarContoller: Tool to autonomously dispatch distributed storage in order to mitigate voltage fluctuation and reduce curtailment. SolarController co-optimizes, in real time, storage dispatch for circuit stability and curtailment reduction, enabling higher penetrations of PV. SolarController is automated, not requiring utility dispatch or management, as Stem hardware senses grid voltage, frequency, customer load, PV production, and power factor. In the end the two products met with different outcomes. SolarScope was tested by potential users, and continues to be used as a foundational platform for partnership with key solar industry partners. SolarController, on the other hand, was successful in lab testing but was not commercialized due to a lack of marketability and lack of interested customer base. Together the development of these two products marked a material step forward for Stem; and a new milestone along the pathway of integration for the solar and storage industries. SolarScope is leading to real, out-of-the-lab project development in storage + solar for the commercial customer sector. Meanwhile SolarController has opened the eyes of regulators and utility executives alike to the potential of distributed solar and by doing so, has moved the conversation forward for the integration of distributed energy resources more broadly on the grid.

25 ENERGY STORAGE↗
DOE OSTI2022

Achieving 50% Energy Savings in Chicago Homes: A Case Study for Advancing Equity and Climate Goals

Since 2019, the National Renewable Energy Laboratory (NREL) and Elevate have collaborated to identify pathways to deep energy retrofits in Chicago's housing stock, document equity implications and co-benefits of this transition, and validate the findings by implementing retrofits in real Chicago homes. This document summarizes our analysis process to model advanced retrofit packages that lead to greater than 50% energy savings in Chicago homes. Based on these findings, we have also developed a roadmap with the City to guide implementation, and are deploying the recommended retrofit packages in real Chicago homes to realize these energy savings. This work was developed in collaboration with two key stakeholders - the City of Chicago and Commonwealth Edison (ComEd) - and funded by the U.S. Department of Energy (DOE). NREL's Residential Buildings team maintains the best-in-class ResStock™ energy model of the U.S. residential building stock. For this work, we calibrated ResStock to Chicago's unique local housing stock to accurately simulate energy use in Chicago homes both for current conditions and with various retrofit scenarios. We simulated a wide range of potential building retrofits covering all aspects of residential energy use and then grouped these into packages based on energy and utility bill savings. ResStock can model diverse building types and housing characteristics, so we're able to observe the range of outcomes that might occur when these upgrades are deployed across the entire housing stock. We can then estimate potential energy savings from an advanced retrofit program on Chicago's housing stock by comparing the modeled energy use before versus after a retrofit. This novel version of ResStock, calibrated to Chicago with data from Elevate, can help City officials, ComEd, and other partners plan for community-scale decarbonization via residential retrofits. Specifically, this work contributes the following project goals: Develop a building retrofit prioritization strategy for Chicago single-family and 2- to 4-unit buildings; Identify neighborhoods and home types that have the highest potential for savings from electrification; and Assess the impact of advanced building retrofits on energy use, utility bills, and CO2 emissions at the city and building level. Although this study is specific to Chicago, its methods and learnings are applicable across the United States. These findings are especially notable for heat pumps and electrification retrofits in cold climates.

building energy modeling↗
DOE OSTI2020

Development and Field Assessment of Transgenic Hybrid Switchgrass for Improved Biofuel Traits

Development of commercially relevant bioenergy switchgrass cultivars requires reducing recalcitrance for bioprocessing without compromising biomass yield. Low-lignin transgenic switchgrass has been produced via down-regulation of caffeic acid O-methyltransferase (COMT), a lignin biosynthetic enzyme, or by over-expression of the MYB4 transcription factor, a repressor of the lignin biosynthetic pathway. The aim of this study was to evaluate parents and selected hybrids obtained from COMT and MYB4 hybrid families under field conditions for agronomic performance and biomass quality. Plant height, width, number of tillers, dry weight, cell wall composition including lignin content, and sugar release were measured after the establishment year (2014) and the second growing season (2015). For COMT hybrids, biomass yield of the transgenic hybrids was similar to or greater than the wild-type parents selected for high biomass. Lignin content of COMT transgenic hybrids was reduced by 10%, S/G ratio decreased by 27%, and sugar release increased between 20% and 44% compared to their wild-type parents. These results indicate that hybridization of COMT with a high-yielding locally selected genotype resulted in both improved agronomic performance and enhanced biomass quality in the offspring. On the other hand, the MYB transgenic hybrid showed a 10% reduction in biomass yield compared with its wild-type parent in year 1, but not in year 2. The lignin S/G ratio was not reduced in MYB transgenic hybrids, nor was sugar release increased. These data indicate that the MYB transgene may not be suitable for an agronomic setting. More testing is needed of transgenic and wild-type, high-biomass selections for use as breeding parents. These results show that combining low-lignin transgenic switchgrass with a breeding and selection program for biomass yield will allow for the deployment of effective transgenes in high-yielding genetic backgrounds.

09 BIOMASS FUELS↗
DOE OSTI2015

A Hard X-ray Study of a Manganese-Terpyridine Dimer Catalyst in a Chromium-Based Metal Organic Framework

Much of today’s scientific research is geared toward discovering clean energy from renewable sources. A promising approach is to split water into its fundamental elements – hydrogen and oxygen. The hydrogen produced from this process is a source of clean energy. Plants carry out this water splitting routinely as a part of photosynthesis, but we cannot do this readily as the reaction requires a lot of energy, negating the value of cleaner and plentiful energy from hydrogen. Adding a catalyst provides an alternative pathway for the reaction so that it can proceed with lower energy input. Many such catalysts have been developed; the one used in this study is manganese based and is called manganese-terpyridine dimer (MnTD). The problem is that when individual molecules of MnTD interact they destroy each other, which limits practical use of the catalyst. However, by placing the catalyst in a Metal Organic Framework (MOF), the molecules of MnTD can be separated so that, in principle, they do not interact with each other and only interact with water. The MOF is essentially a repetition of boxes, and each box should contain one MnTD molecule. However, preliminary studies showed that a different molecule, not MnTD, may be inside the boxes. My research focused on identifying which molecules are present in the MOF. The primary method of analysis used was x-ray powder diffraction, a technique in which x-rays are scattered by a sample, and the intensity of the scattered radiation is measured as a function of scattering angle. Three samples were analyzed; one contained only the MOF, one contained the MOF and catalyst before catalysis, and one contained the MOF and catalyst during catalysis. The diffraction experiments were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL) at SLAC National Accelerator Laboratory. Initial results revealed that the MOF structure falls apart during catalysis. To further analyze the data, I used several computer programs, including GSAS II, FOX, and VESTA. These programs allowed me to create maps that showed regions of electron density within the MOF and gave me clues as to which molecules were present. I found that MnTD was not the catalytic molecule in the MOF. The preliminary studies showed that manganese oxide is likely present, which is consistent with by data. However, the catalytic rate for this system is much higher than that reported for manganese oxide, and thus future studies are needed to verify the identity of the catalytic molecule and determine the reasons for its unusually high rate of catalysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

Photooxidation and Photodesorption in the Photochemistry of Isobutene on TiO2(110)

The photochemistry of isobutene was examined on the rutile TiO2(110) surface as a function of the surface pretreatment condition and irradiation temperature using temperature programmed desorption (TPD) and photon stimulated desorption (PSD). Isobutene adsorbs molecularly on the clean TiO2(110) surface without detectable thermal decomposition. Preadsorption of oxygen, either as atoms or chemisorbed molecules, did not promote thermal reactions with isobutene, but instead blocked isobutene adsorption sites. Ultraviolet (UV) light irradiation of isobutene adsorbed on the clean surface led to depletion through photodesorption without significant photodecomposition. Isobutene PSD yields increased with increasing surface temperature suggesting that activated molecules sample their physisorbed potential energy surface during photodesorption. Preadsorption of oxygen promoted partial photooxidation of adsorbed isobutene to acetone, methacrolein and isobutanal. Acetone was only detected when molecular oxygen was present, indicating that O2 addition occurred across the C=C bond. In contrast, results from use of D6-isobutene indicated that coadsorption with either O adatoms or O2 molecules led to photochemical production of methacrolein (and likely isobutanal) through C-H bond cleavage on a methyl group. Irradiation an adlayer comprised of isobutene isolated from the surface by 1 ML of preadsorbed O2 showed the most photoconversion of isobutene, which suggests that photoactivation of adsorbed O2 is a key step in partial photooxidation of isobutene. Comparison of the isobutene PSD and oxidation product yields as a function of surface temperature between 20 and 120 K indicates a competition between photooxidation and photodesorption that varies with temperature. ‘Direct’ charge transfer events between isobutene and the surface, favored at higher temperature, compete with partial oxidation pathways initiated by ‘indirect’ activation of isobutene by O2, which is favored at low temperature. Access of O2 to the surface is critical to achieving desired isobutene photooxidation rates and products, and isobutene photodesorption may provide a means of regulating the isobutene surface coverage. Work reported here was supported by the U.S. Department of Energy, Office of Basic Energy Science, Division of Chemical Sciences, Geosciences, and Biosciences, and performed in the Williams R. Wiley Environmental Molecular Science Laboratory (EMSL), a Department of Energy user facility funded by the Office of Biological and Environmental Research. Pacific Northwest National Laboratory is a multiprogram national laboratory operated for the U.S. Department of Energy by the Battelle Memorial Institute under contract DEAC05-76RL01830.

Environmental Molecular Sciences Laboratory↗
NASA NTRS1999

T cell activation responses are differentially regulated during clinorotation and in spaceflight

Studies of T lymphocyte activation with mitogenic lectins during spaceflight have shown a dramatic inhibition of activation as measured by DNA synthesis at 72 h, but the mechanism of this inhibition is unknown. We have investigated the progression of cellular events during the first 24 h of activation using both spaceflight microgravity culture and a ground-based model system that relies on the low shear culture environment of a rotating clinostat (clinorotation). Stimulation of human peripheral blood mononuclear cells (PBMCs) with soluble anti-CD3 (Leu4) in clinorotation and in microgravity culture shows a dramatic reduction in surface expression of the receptor for IL-2 (CD25) and CD69. An absence of bulk RNA synthesis in clinorotation indicates that stimulation with soluble Leu4 does not induce transition of T cells from G0 to the G1 stage of the cell cycle. However, internalization of the TCR by T cells and normal levels of IL-1 synthesis by monocytes indicate that intercellular interactions that are required for activation occur during clinorotation. Complementation of TCR-mediated signaling by phorbol ester restores the ability of PBMCs to express CD25 in clinorotation, indicating that a PKC-associated pathway may be compromised under these conditions. Bypassing the TCR by direct activation of intracellular pathways with a combination of phorbol ester and calcium ionophore in clinorotation resulted in full expression of CD25; however, only partial expression of CD25 occurred in microgravity culture. Though stimulation of purified T cells with Bead-Leu4 in microgravity culture resulted in the engagement and internalization of the TCR, the cells still failed to express CD25. When T cells were stimulated with Bead-Leu4 in microgravity culture, they were able to partially express CD69, a receptor that is constitutively stored in intracellular pools and can be expressed in the absence of new gene expression. Our results suggest that the inhibition of T cell proliferative response in microgravity culture is a result of alterations in signaling events within the first few hours of activation, which are required for the expression of important regulatory molecules.

NASA Experiment Number 9403079 1/2↗
NASA NTRS2000

The auxin-resistant diageotropica mutant of tomato responds to gravity via an auxin-mediated pathway

Hypocotyls of the diageotropica (dgt) mutant of tomato (Lycopersicon esculentum Mill.) do not elongate in response to exogenous auxin, but can respond to gravity. This appears paradoxical in light of the Cholodny-Went hypothesis, which states that shoot gravicurvature results from asymmetric stimulation of elongation by auxin. While light-grown dgt seedlings can achieve correct gravitropic reorientation, the response is slow compared to wild-type seedlings. The sensitivity of dgt seedlings to inhibition of gravicurvature by immersion in auxin or auxin-transport inhibitors is similar to that of wild-type plants, indicating that both an auxin gradient and auxin transport are required for the gravitropic response and that auxin uptake, efflux, and at least one auxin receptor are functional in dgt. Furthermore, dgt gravicurvature is the result of asymmetrically increased elongation as would be expected for an auxin-mediated response. Our results suggest differences between elongation in response to exogenous auxin (absent in dgt) and elongation in response to gravistimulation (present but attenuated in dgt) and confirm the presence of two phases during the gravitropic response, both of which are dependent on functional auxin transport.

Non-NASA Center↗
NASA NTRS2010

Risk as a Driver for Innovation

The Space Life Sciences directorate (SLSD) and Human Research Program (HRP) at NASA Johnson Space Center has implemented a system for managing human systems risks. These risks are defined as the health and performance risks posed to crew during and after spaceflight. Identification and evaluation of these risks has led to the identification of gaps in knowledge about the risks as well as gaps in technology needed to mitigate them. Traditional routes of closing technology gaps have, in some cases, proven to be too slow when a solution was required quickly. Therefore, certain gaps were used to drive the development of "challenges" for the scientific community. Partnering with open innovation service providers such as InnoCentive and Yet2.com, SLSD and HRP have decreased the amount of time from identification of a need to the evaluation of a solution. Although not all proposed solutions will result in a risk mitigation strategy or tool, the process has allowed faster evaluation of proposed solutions providing the researcher the ability to move to another possible solution if the first does not sufficiently address the problem. Moreover, this process engages the community outside of NASA and broadens the population from which to draw solutions. In the traditional grant funding structure, only those in the specific field will apply for the grant. However, using open innovation, solutions can come from individuals in many different fields. This can expand the general view of a field (way of thinking within a field) and the application of solutions form new fields while providing a pathway for the acquisition of novel solutions or refinements of current mitigations. Identification of the human systems risks has helped drive the development and evaluation of innovative solutions as well as engaging a broader scientific audience in working with NASA.

Davis, Jeff↗
NASA NTRS1988

An extreme-halophile archaebacterium possesses the interlock type of prephenate dehydratase characteristic of the Gram-positive eubacteria

The focal point of phenylalanine biosynthesis is a dehydratase reaction which in different organisms may be prephenate dehydratase, arogenate dehydratase, or cyclohexadienyl dehydratase. Gram-positive, Gram-negative, and cyanobacterial divisions of the eubacterial kingdom exhibit different dehydratase patterns. A new extreme-halophile isolate, which grows on defined medium and is tentatively designated as Halobacterium vallismortis CH-1, possesses the interlock type of prephenate dehydratase present in Gram-positive bacteria. In addition to the conventional sensitivity to feedback inhibition by L-phenylalanine, the phenomenon of metabolic interlock was exemplified by the sensitivity of prephenate dehydratase to allosteric effects produced by extra-pathway (remote) effectors. Thus, L-tryptophan inhibited activity while L-tyrosine, L-methionine, L-leucine and L-isoleucine activated the enzyme. L-Isoleucine and L-phenylalanine were effective at micromolar levels; other effectors operated at mM levels. A regulatory mutant selected for resistance to growth inhibition caused by beta-2-thienylalanine possessed an altered prephenate dehydratase in which a phenomenon of disproportionately low activity at low enzyme concentration was abolished. Inhibition by L-tryptophan was also lost, and activation by allosteric activators was diminished. Not only was sensitivity to feedback inhibition by L-phenylalanine lost, but the mutant enzyme was now activated by this amino acid (a mutation type previously observed in Bacillus subtilis). It remains to be seen whether this type of prephenate dehydratase will prove to be characteristic of all archaebacteria or of some archaebacterial subgroup cluster.

NASA Discipline Number 52-30↗
NASA NTRS1992

Light regulation of the growth response in corn root gravitropism

Roots of Merit variety corn (Zea mays L.) require red light for orthogravitropic curvature. Experiments were undertaken to identify the step in the pathway from gravity perception to asymmetric growth on which light may act. Red light was effective in inducing gravitropism whether it was supplied concomitant with or as long as 30 minutes after the gravity stimulus (GS). The presentation time was the same whether the GS was supplied in red light or in darkness. Red light given before the GS slightly enhanced the rate of curvature but had little effect on the lag time or on the final curvature. This enhancement was expanded by a delay between the red light pulse and the GS. These results indicate that gravity perception and at least the initial transduction steps proceed in the dark. Light may regulate the final growth (motor) phase of gravitropism. The time required for full expression of the light enhancement of curvature is consistent with its involvement in some light-stimulated biosynthetic event.

NASA Discipline Number 40-50↗
NASA NTRS2010

Human Research Program Space Radiation Standing Review Panel (SRP)

The Space Radiation Standing Review Panel (SRP) met at the NASA Johnson Space Center (JSC) on December 9-11, 2009 to discuss the areas of current and future research targeted by the Space Radiation Program Element (SRPE) of the Human Research Program (HRP). Using evidence-based knowledge as a background for identified risks to astronaut health and performance, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Space Radiation SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the SRP's review. The SRP was requested to evaluate the practicality of the proposed efforts in light of the demands placed on the HRP. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the SRP charge. The SRP made a final debriefing to the HRP Program Scientist, Dr. John B. Charles, on December 11, 2009. The SRP noted that current SRPE strategy is properly science-based and views this as the best assurance of the likelihood that answers to the questions posed as gaps in knowledge can be found, that the uncertainty in risk estimates can be reduced, and that a solid, cost-effective approach to risk reduction solutions is being developed. The current approach of the SRPE, based on the use of carefully focused research solicitations, requiring thorough peer-review and approaches demonstrated to be on the path to answering the NASA strategic questions, addressed to a broad extramural community of qualified scientists, optimally positioned to take advantage of serendipitous discoveries and to leverage scientific advances made elsewhere, is sound and appropriate. The SRP viewed with concern statements by HRP implying that the only science legitimately deserving support should be "applied" or, in some instances that the very term "research" might be frowned upon. We understand the desire of management to ensure that research stay focused on mission objectives, but the terms used are code words fraught with different meaning for scientists. Such expressions, taken at face value, convey a profoundly flawed view of science, can easily lead down counterproductive paths, and have the potential to irretrievably corrupt NASA requirements. The SRP understands and endorses the mandate to keep research efforts focused on the mission needs. However, thoughtful application of knowledge gained by understanding the mechanisms and pathways of biological effects cannot be replaced.

Woloschak, Gayle↗
DOE OSTI2022

A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (n rs495828 = 53 and n rs505922 = 59); strongest association with venous embolism, odds ratio (OR rs495828 1.33 (p = 1.32 x 10 –199 ), and thrombosis OR rs505922 1.33, p = 2.2 x10 -265 . Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10 –191 ; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10 –12 . The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10 -23 , lupus OR 0.84, p = 3.97 x 10 –06 . PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10 –13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

59 BASIC BIOLOGICAL SCIENCES↗