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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 595 records · Page 33
All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

ASPIRE Aerodynamic Models and Flight Performance

The Advanced Supersonic Parachute Inflation Research Experiments (ASPIRE) project waslaunched to develop the capability for testing supersonic parachutes at Mars-relevant conditions.Three initial parachute tests, targeted as a risk-reduction activity for NASA's upcoming Mars2020 mission, successfully tested two candidate parachute designs and provided valuable data onparachute inflation, forces, and aerodynamic behavior. Design of the flight tests depended onflight mechanics simulations which in turn required aerodynamic models for the payload, andthe parachute. Computational Fluid Dynamics (CFD) was used to generate these models preflightand they are compared against the flight data after the tests. For the payload, thereconstructed aerodynamic behavior is close to the pre-flight predictions, but the uncertaintiesin the reconstructed data are high due to the low dynamic pressures and accelerations duringthe flight period of comparison. For the parachute, the predicted time to inflation agrees wellwith the pre-flight model; the peak aerodynamic force and the steady state drag on the parachuteare within the bounds of the pre-flight models, even as the models over-predict the parachutedrag at supersonic Mach numbers. Notably, the flight data do not show the transonic dragdecrease predicted by the pre-flight model. The ASPIRE flight tests provide previouslyunavailable valuable data on the performance of a large full-scale parachute behind a slenderleading body at Mars-relevant Mach number, dynamic pressure and parachute loads. TheASPIRE results are used to propose a new model for the parachute drag behind slender bodiesto aid future experiments.

Muppidi, Suman↗
NASA NTRS2019

ASPIRE Aerodynamic Models and Flight Performance

The Advanced Supersonic Parachute Inflation Research Experiments (ASPIRE) project waslaunched to develop the capability for testing supersonic parachutes at Mars-relevant conditions.Three initial parachute tests, targeted as a risk-reduction activity for NASA's upcomingMars2020 mission, successfully tested two candidate parachute designs and provided valuabledata on parachute inflation, forces, and aerodynamic behavior. Design of the flight tests dependedon flight mechanics simulations which in turn required aerodynamic models for the payload, andthe parachute. Computational Fluid Dynamics (CFD) was used to generate these models preflightand are compared against the flight data after the tests. For the payload, the reconstructedaerodynamic behavior is close to the pre-flight predictions, but the uncertainties in thereconstructed data are high due to the low dynamic pressures and accelerations during the flightperiod of comparison. For the parachute, the predicted time to inflation agrees well with the preflightmodel; the peak aerodynamic force and the steady state drag on the parachute are withinthe bounds of the pre-flight models, even as the models over-predict the parachute drag atsupersonic Mach numbers. Notably, the flight data does not show the transonic drag decreasepredicted by the pre-flight model. The ASPIRE flight tests provide previously unavailablevaluable data on the performance of a large full-scale parachute behind a slender leading bodyat Mars-relevant Mach number, dynamic pressure and parachute loads. This data is used topropose a new model for the parachute drag behind slender bodies to aid future experiments.

Muppidi, Suman↗
NASA NTRS2019

Overview of the ASPIRE project's supersonic flight tests of a strengthened DGB parachute

The Advanced Supersonic Parachute Inflation Research Experiments (ASPIRE) project is aimed at developing and exercising a capability for testing supersonic parachutes at Mars-relevant conditions. The initial flights for ASPIRE were targeted as a risk-reduction activity for NASA’s upcoming Mars2020 mission. For this effort, two candidate Disk-GapBand (DGB) parachute designs were tested at Mach number and dynamic pressure conditions relevant to Mars2020. The two parachutes under investigation were a build-to-print version of the DGB used by the Mars Science Laboratory and a strengthened version of this parachute that has the same geometry but differs in materials and construction.

Clark, Ian G.↗
NASA NTRSDate not supplied

Wildfire Emergency Response Hazard Extraction and Analysis of Trends (HEAT) through Natural Language Processing and Time Series

Emerging wildfire operations aim to improve safety and performance through the integration of technologies including UAS and UTM. Recent advances in natural language processing (NLP) techniques, as well as the availability of wildfire incident reports, has made possible a large-scale analysis of wildfire hazards and trends. Identifying longitudinal trends will help us target risk mitigation and safety management activities. Note: This presentation does not include sound please disregard icon.

Sequoia R. Andrade↗
NASA NTRS2021

Commanding Curiosity from the Couch: MSL Remote Operations, Challenges, and Path Ahead

This paper describes how the Mars ScienceLaboratory (MSL) project prepared for and successfully beganCuriosity rover Mars operations from their homes in responseto the COVID-19 work-from-home orders. In a very shortperiod, the team developed procedures and executed a remoteoperations readiness test in parallel with the team's support fornominal operations. Continuing regular rover operations withan entirely remote team had not previously been consideredfeasible due to a variety of factors. These included both thehuman factors, such as multiple concurrent person-to-personinteractions of the uplink planning team, as well as technicalfactors, such as reliance on powerful workstations dedicated tographically intensive software tools used for planning. The testwas conducted on March 12th, with both the downlink anduplink teams successfully simulating a near full planning day.The JPL administration announced the transition to mandatorytelework on Monday, March 16th. MSL stood down the uplinkplanning originally scheduled for the next day while downlinkcontinued monitoring the rover. Full operations then resumedper schedule with nearly the entire operations team teleworkingon Friday, March 20th, during which the team planned roveractivities for three Martian days (sols). These activities includedthe successful drilling of the "Edinburgh" rock target, a highlycomplex contact science activity.As of October 1st, 2020, the Mars Science Laboratory missionoperations team has conducted 88 remote tactical uplink shiftsfor a total of 190 sols of planned rover activity, which accountsfor more than 6% of the mission to date. In this period the roverhas completed four drilling campaigns and driven over 1150meters towards its next major science target – a sulfate bearinggeologic unit at the foot of Mount Sharp. Success has not beenwithout its challenges. Many of these have been addressed whileothers will remain in some form until the team can safely returnto JPL, which in turn is the largest challenge for the future.

Stroupe, Ashley↗
DOE OSTI2023

Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity

Novel therapeutic monoclonal antibodies (MAbs) must accommodate comprehensive breadth of activity against diverse sarbecoviruses and high neutralization potency to overcome emerging variants. Here, in this study, we report the crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) in complex with MAb WRAIR-2063, a moderate-potency neutralizing antibody with exceptional sarbecovirus breadth, that targets the highly conserved cryptic class V epitope. This epitope overlaps substantially with the spike protein N-terminal domain (NTD) -interacting region and is exposed only when the spike is in the open conformation, with one or more RBDs accessible. WRAIR-2063 binds the RBD of SARS-CoV-2 WA-1, all variants of concern (VoCs), and clade 1 to 4 sarbecoviruses with high affinity, demonstrating the conservation of this epitope and potential resiliency against variation. We compare structural features of additional class V antibodies with their reported neutralization capacity to further explore the utility of the class V epitope as a pan-sarbecovirus vaccine and therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A Multi-Objective Bayesian Optimized Human Assessed Multi-Target Generated Spectral Recommender System for Rapid Pareto Discoveries of Material Properties

Optimization for different tasks like material characterization, synthesis, and functional properties for desired applications over multi-dimensional control parameter and function spaces need a rapid strategic search through active learning. However, in all cases prior to optimization, the target material properties are assumed known and fixed, which mostly deviates from real-world scenarios in material synthesis. This can be critical for running expensive experiments on new materials, when the experimental results are fuzzy for any scientific outcomes due to improper target setting, ultimately wasting time and cost. The failure rate and cost are even higher over exploring on multi-target space, where we want to learn the pareto among multiple properties, to jointly optimize during material synthesis for desired applications. To address the challenge, here we introduce the human-operator attempt flexibility in the active learning based automated experiment framework, with generating multiple human assessed targets through a voting-based recommender system during real-time microscope measurements over the large material image space, sequentially learn/update multiple desired targets through a weighting system, and adaptively search in multiple material properties functional space for non-dominated pareto discoveries to maximize the custom structural similarity based acquisition function. We term this a multi-objective Bayesian optimized human assessed multi-target generated spectral recommender systems (MOBO-HAM-SRS). The approach has been demonstrated to peizoresponse force spectroscopy of a ferroelectric thin film, exploring with different kernels and acquisition functions. This work shows an advancement towards human-AI collaborated automated experiments, steering optimization trajectories through human overpowering AI at the early stage when uncertainty is high and AI overpowering human at the later stage with rapid exploration towards optimal goal, following human-assessed multiple targets properties.

Biswas, Arpan↗
NASA NTRS2024

The Analogs for VENus’ GEologically Recent Surfaces (AVENGERS) Initiative: Updates and New Target Areas

Several missions to Venus have been recently selected for launch, opening a new era for the exploration of the planet. One of the key questions that future missions need to address is the rate and style of present-day volcanic activity on Venus. To this regard, an important target on Venus is certainly represented by the young topographic rises, which can be interpreted as the surface expression of underlying mantle plumes. These areas can be considered as the geologically youngest regions of Venus, being characterized by recent volcanic and tectonic activity. Studying areas of active volcanism and tectonism on Venus is crucial as it can reveal clues to the geologic past of the planet, as well as provide information about the volatile content of its interior and about the formation of its dense atmosphere. The “Analogs for VENus’ GEologically Recent Surfaces” (AVENGERS) initiative aims to select and analyze a number of terrestrial analog sites for the comparative study of recent and possibly ongoing volcanic activity on Venus. In addition to its scientific importance, the AVENGERS initiative acts as a bridge for international scientific collaboration, including selected mission teams.

P D'Incecco↗
DOE OSTI2021

Endothelium-specific endothelin-1 expression promotes pro-inflammatory macrophage activation by regulating miR-33/NR4A axis

The hallmark of atherogenesis is characterized as endothelial dysfunction and subsequent macrophage activation. Although our previous study has demonstrated that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying mechanism remains deeply investigation. Enhanced atherosclerotic plaques were observed in endothelium-specific ET-1 overexpression ApoE{sup −/-} mice (eET-1/ApoE{sup −/-}) concomitant with increased secretion of pro-inflammatory adhesion molecules and cytokines. The conditional media used for culturing human umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to OX-LDL stimulation, was collected and utilized for bone marrow-derived macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression related to classical M1 macrophages but decreased alternative activated M2 macrophages genes expression in macrophage culturing with the conditional media. Furthermore, consistent regulations of macrophage polarization were observed using isolated exosomes from the conditional media. More importantly, we noticed that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, while bioinformatics analysis further indicated that miR-33 directly targeted NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such effects could be reversed by ET-1 knockdown. Taken together, our study indicated that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to macrophages and subsequently promote pro-inflammatory macrophage activation by directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A axis was the important mechanism underlying the effect of ET-1 on macrophage activation and indicated that ET-1 may act as a promising target for atherosclerosis management.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR

Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. SPRED1 and NF1 loss-of-function mutations occur across multiple cancer types and developmental diseases. Analysis of the neurofibromin-SPRED1 interface provides a rationale for mutations observed in Legius syndrome and suggests why SPRED1 can bind to neurofibromin but no other RasGAPs. We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Data-driven prediction of α IIb β 3 integrin activation paths using manifold learning and deep generative modeling

The integrin heterodimer is a transmembrane protein critical for driving cellular process and is a therapeutic target in the treatment of multiple diseases linked to its malfunction. Activation of integrin involves conformational transitions between bent and extended states. Some of the conformations that are intermediate between bent and extended states of the heterodimer have been experimentally characterized, but the full activation pathways remain unresolved both experimentally due to their transient nature and computationally due to the challenges in simulating rare barrier crossing events in these large molecular systems. An understanding of the activation pathways can provide new fundamental understanding of the biophysical processes associated with the dynamic interconversions between bent and extended states and unveil new putative therapeutic targets. In this work, we apply nonlinear manifold learning to coarse-grained molecular dynamics simulations of bent, extended, and two intermediate states of αI I b β3 integrin to learn a low-dimensional embedding of the configurational phase space. We then train deep generative models to learn an inverse mapping between the low-dimensional embedding and high-dimensional molecular space and use these models to interpolate the molecular configurations constituting the activation pathways between the experimentally characterized states. Furthermore, this work furnishes plausible predictions of integrin activation pathways and reports a generic and transferable multi-scale technique to predict transition pathways for biomolecular systems.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme–PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

LBNF Target Complex Remote Handling

The Long Baseline Neutrino Facility (LBNF) near site at the Fermilab campus in Illinois, USA includes a target complex which houses a 1.5 – 1.8m long graphite neutrino production target, a pre-target baffle, three neutrino focusing horns (A,B,C), and a decay pipe 200m in length leading to an energy absorber / beam dump housed in an adjacent absorber building. The prompt dose rates are such that the Target Hall must be unoccupied while beam is on target. During maintenance periods, the Target Hall can be occupied by trained personnel. However, residual dose rates of activated components necessitate certain operations, such as the annual replacement of the target, be executed remotely by personnel located in a shielded room within the Target Hall. This presentation covers details designed into the infrastructure, equipment, and procedures to allow for successful execution of remote handling operations.

43 PARTICLE ACCELERATORS↗
DOE OSTI2020

Activity–Based Protein Profiling of Bile Salt Hydrolysis in the Human Gut Microbiome with Beta–Lactam or Acrylamide–Based Probes

Microbial bile salt hydrolases (BSHs) found in the intestine catalyze the deconjugation of taurine– and glycine–linked bile salts produced in the liver. The resulting bile salts are biological detergents and are critical in aiding lipophilic nutrient digestion. Therefore, the activity of BSHs in the gut microbiome is directly linked to human metabolism and overall health. Bile salt metabolism has also been associated with disease phenotypes such as liver and colorectal cancer. In order to reshape the gut microbiome to optimize bile salt metabolism, tools to characterize and quantify these processes must exist to enable a much–improved understanding of how metabolism goes awry in the face of disease, and how it can be improved through an altered lifestyle and environment. Furthermore, it is necessary to attribute metabolic activity to specific members and BSHs within the microbiome. To this end, we have developed activity–based probes with two different reactive groups to target bile salt hydrolases. Finally, these probes bind similarly to the authentic bile salt substrates, and we demonstrate enzyme labeling of active bile salt hydrolases by using purified protein, cell lysates, and in human stool.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition

Selective inhibition of the more than 100 S1 family serine proteases is a long-standing challenge due to their active site similarity. Mesotrypsin, implicated in cancer progression, exemplifies these difficulties; no current inhibitors achieve selectivity over other human trypsins. We found an unexpected autoinhibited conformation of mesotrypsin via x-ray crystallography, revealing a cryptic pocket adjacent to the active site. Using high-throughput virtual screening targeting this cryptic pocket, we identified a conformationally selective small-molecule inhibitor that stabilizes the inactive state of mesotrypsin. This inhibitor demonstrates selectivity for mesotrypsin over other trypsins. Our findings challenge the accepted view of digestive trypsins as constitutively active enzymes lacking potential for allosteric regulation. Furthermore, analyses of other structures suggest that dynamic sampling of closed states with analogous allosteric cryptic pockets appears widespread among S1 serine proteases. These observations point to a potentially generalizable strategy to achieve selective inhibition, offering broad implications for drug development targeting serine proteases in cancer and other diseases.

Coban, Matt↗
DOE OSTI2022

Preparation of Actinide Targets at Oregon State University

In this paper, we describe the preparation of actinide targets at Oregon State University. The preparation of the actinide fluorides is done by an aqueous precipitation procedure with yields of greater than 90%. A dual glove box system is used for the preparation of the fluorides of the high specific activity actinides and the subsequent vapor deposition. We compare and contrast targets made by vapor deposition and molecular plating. We discuss some new data on the structure of actinide targets.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1985

Implementing quality/productivity improvement initiatives in an engineering environment

Quality/Productivity Improvement (QPI) initiatives in the engineering environment at McDonnell Douglas-Houston include several different, distinct activities, each having its own application, yet all targeted toward one common goal - making continuous improvement a way of life. The chief executive and the next two levels of management demonstrate their commitment to QPI with hands-on involvement in several activities. Each is a member of a QPI Council which consists of six panels - Participative Management, Communications, Training, Performance/Productivity, Human Resources Management and Strategic Management. In addition, each manager conducts Workplace Visits and Bosstalks, to enhance communications with employees and to provide a forum for the identification of problems - both real and perceived. Quality Circles and Project Teams are well established within McConnel Douglas as useful and desirable employee involvement teams. The continued growth of voluntary membership in the circles program is strong evidence of the employee interest and management support that have developed within the organization.

Ruda, R. R.↗