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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 811 records · Page 45
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Unexpected role of a conserved domain in the first extracellular loop in G protein-coupled receptor trafficking

Highlights: • Most Class A GPCRs contain a conserved WxFG motif. • Substitution of the W with a non-aromatic amino acid disrupts GPCR functioning. • Disrupted GPCR functioning is the due to aberrant plasma membrane localization. G protein-coupled receptors are the largest superfamily of cell surface receptors in the Metazoa and play critical roles in transducing extracellular signals into intracellular responses. This action is mediated through conformational changes in the receptor following ligand binding. A number of conserved motifs have critical roles in GPCR function, and here we focus on a highly conserved motif (WxFG) in extracellular loop one (EL1). A phylogenetic analysis documents the presence of the WxFG motif in ∼90% of Class A GPCRs and the motif is represented in 17 of the 19 Class A GPCR subfamilies. Using site-directed mutagenesis, we mutagenized the conserved tryptophan residue in eight receptors which are members of disparate class A GPCR subfamilies from different taxa. The modification of the Drosophila leucokinin receptor shows that substitution of any non-aromatic amino acid for the tryptophan leads to a loss of receptor function. Additionally, leucine substitutions at this position caused similar signaling defects in the follicle-stimulating hormone receptor (FSHR), Galanin receptor (GALR1), AKH receptor (AKHR), corazonin receptor (CRZR), and muscarinic acetylcholine receptor (mACHR1). Visualization of modified receptors through the incorporation of a fluorescent tag revealed a severe reduction in plasma membrane expression, indicating aberrant trafficking of these modified receptors. Taken together, these results suggest a novel role for the WxFG motif in GPCR trafficking and receptor function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Beyond sequence similarity: toward function-based screening of nucleic acid synthesis

Synthetic nucleic acids are a key input to modern biotechnology, yet they represent dual-use materials that require robust screening to mitigate biosecurity risks. The prevailing screening paradigm, which identifies sequences of concern (SoCs) through sequence similarity to controlled pathogens and toxins, may not fully capture risks posed by AI tools that can decouple biomolecular function from reliance on known sequences. Rapidly advancing biodesign capabilities enable the generation of genes and proteins that might evade sequence-based detection. We highlight the critical need for function-based screening approaches that can detect sequences capable of hazardous biological functions, regardless of similarity to known SoCs. We examine the feasibility of function-based screening with an initial focus on proteins, arguing that, while protein sequence space is vast, biologically functional proteins are significantly constrained by biophysical and biochemical requirements that can be learned and modeled. We propose a concrete implementation framework organized along a continuum of complexity, starting with toxins as the most tractable targets before expanding to more complex pathogenic functions. We then discuss open challenges and describe a research and development strategy to address them.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2009

Functional Task Test (FTT)

This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

Bloomberg, Jacob J.↗
DOE OSTI2021

Artificial intelligence techniques for integrative structural biology of intrinsically disordered proteins

Here, we outline recent developments in artificial intelligence (AI) and machine learning (ML) techniques for integrative structural biology of intrinsically disordered proteins (IDP) ensembles. IDPs challenge the traditional protein structure-function paradigm by adapting their conformations in response to specific binding partners leading them to mediate diverse, and often complex cellular functions such as biological signaling, self-organization and compartmentalization. Obtaining mechanistic insights into their function can therefore be challenging for traditional structural determination techniques. Often, scientists have to rely on piecemeal evidence drawn from diverse experimental techniques to characterize their functional mechanisms. Multiscale simulations can help bridge critical knowledge gaps about IDP structure-function relationships - however, these techniques also face challenges in resolving emergent phenomena within IDP conformational ensembles. We posit that scalable statistical inference techniques can effectively integrate information gleaned from multiple experimental techniques as well as from simulations, thus providing access to atomistic details of these emergent phenomena.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Spacecraft Software Maintenance: An Effective Approach to Reducing Costs and Increasing Science Return

Flight software is a mission critical element of spacecraft functionality and performance. When ground operations personnel interface to a spacecraft, they are typically dealing almost entirely with the capabilities of onboard software. This software, even more than critical ground/flight communications systems, is expected to perform perfectly during all phases of spacecraft life. Due to the fact that it can be reprogrammed on-orbit to accommodate degradations or failures in flight hardware, new insights into spacecraft characteristics, new control options which permit enhanced science options, etc., the on- orbit flight software maintenance team is usually significantly responsible for the long term success of a science mission. Failure of flight software to perform as needed can result in very expensive operations work-around costs and lost science opportunities. There are three basic approaches to maintaining spacecraft software--namely using the original developers, using the mission operations personnel, or assembling a center of excellence for multi-spacecraft software maintenance. Not planning properly for flight software maintenance can lead to unnecessarily high on-orbit costs and/or unacceptably long delays, or errors, in patch installations. A common approach for flight software maintenance is to access the original development staff. The argument for utilizing the development staff is that the people who developed the software will be the best people to modify the software on-orbit. However, it can quickly becomes a challenge to obtain the services of these key people. They may no longer be available to the organization. They may have a more urgent job to perform, quite likely on another project under different project management. If they havn't worked on the software for a long time, they may need precious time for refamiliarization to the software, testbeds and tools. Further, a lack of insight into issues related to flight software in its on-orbit environment, may find the developer unprepared for the challenges. The second approach is to train a member of the flight operations team to maintain the spacecraft software. This can prove to be a costly and inflexible solution. The person assigned to this duty may not have enough work to do during a problem free period and may have too much to do when a problem arises. If the person is a talented software engineer, he/she may not enjoy the limited software opportunities available in this position; and may eventually leave for newer technology computer science opportunities. Training replacement flight software personnel can be a difficult and lengthy process. The third approach is to assemble a center of excellence for on-orbit spacecraft software maintenance. Personnel in this specialty center can be managed to support flight software of multiple missions at once. The variety of challenges among a set of on-orbit missions, can result in a dedicated, talented staff which is fully trained and available to support each mission's needs. Such staff are not software developers but are rather spacecraft software systems engineers. The cost to any one mission is extremely low because the software staff works and charges, minimally on missions with no current operations issues; and their professional insight into on-orbit software troubleshooting and maintenance methods ensures low risk, effective and minimal-cost solutions to on-orbit issues.

Shell, Elaine M.↗
DOE OSTI2016

Functional Imaging of the Foot with Perfusion Angiography in Critical Limb Ischemia

PurposeTo report on the first clinical experience with perfusion angiography (PA) of the foot in patients with chronic critical limb ischemia.Materials and MethodsPA is a post-processing software algorithm and no extra digital subtraction angiography (DSA) has to be performed for this analysis. The data used to test the feasibility of PA were obtained from a consecutive group of 89 patients with CLI who were treated with standard below the knee angioplasty and 12 separate patients who were not suitable for endovascular revascularization.ResultsMotion artifacts in the dataset of the DSA made post-procedural analysis impossible in 10 % intervention. In the majority of patients (59/68) PA showed an increase in volume flow in the foot after successful angioplasty of the crural vessels. However, in 9/68 patients no increase was seen after successful angioplasty. With the use of a local administered competitive α-adrenergic receptor antagonist, it is also possible to test and quantify the capillary resistance index which is a parameter for the remaining functionality of the microcirculation in CLI patients.ConclusionPA might be used as a new endpoint for lower limb revascularization and can also be used to test the functionality the microcirculation to identify sub-types of patients with CLI. Clinical evaluation and standardization of PA is mandatory before introduction in daily practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice

Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells

Highlights: • Rheb deficiency causes abnormalities in myeloid lineage cells. • Rheb deficiency impairs HSC-derived hematopoiesis post-transplantation. • Unlike Raptor, Rheb is dispensable for HSC self-renewal at steady-state. The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's energy status and environmental levels of nutrients and growth factors. In response, mTORC1 mediates signaling that controls protein translation and cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it remains unclear which upstream stimuli regulate mTORC1 activity in the context of hematopoietic stem cells (HSC) maintenance in vivo. In this study, we investigated the function of Rheb, a critical regulator of mTORC1 activity controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady-state and in HSC-derived hematopoiesis post-transplantation. In contrast to the severe hematopoietic dysfunction caused by Raptor deletion, which completely inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable hematopoietic failure. Lack of Rheb caused abnormalities in myeloid cells but did not have impact on hematopoietic regeneration in mice subjected to injury by irradiation. As previously reported, Rheb deficiency resulted in defective HSC-derived hematopoiesis post-transplantation. However, while Raptor is essential for HSC competitiveness in vivo, Rheb is dispensable for HSC maintenance under physiological conditions, indicating that the PI3K-AKT-TSC pathway does not contribute to mTORC1 activity for sustaining HSC self-renewal activity at steady-state. Thus, the various regulatory elements that impinge upstream of mTORC1 activation pathways are differentially required for HSC homeostasis in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH’s global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities making them mutually exclusive between NER and transcription initiation. By sequentially coordinating the XPB and XPD DNA-unwinding activities, the switch ensures precise DNA incision in NER. Mapping TFIIH disease mutations onto network models reveals clustering into distinct mechanistic classes, affecting translocase functions, protein interactions and interface dynamics.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1997

Free Radicals Generated by Ionizing Radiation Signal Nuclear Translocation of p53

The p53 tumor suppressor is a transcription factor that regulates several pathways, which function collectively to maintain the integrity of the genome. Nuclear localization is critical for wild-type function. However, the signals that regulate subcellular localization of p53 have not been identified. Here, we examine the effect of ionizing radiation on the subcellular localization of p53 in two cell lines in which p63 is normally sequestered in the cytoplasm and found that ionizing radiation caused a biphasic translocation response. p53 entered the nucleus 1-2 hours postirradiation (early response), subsequently emerged from the nucleus, and then again entered the nucleus 12-24 hours after the cells had been irradiated (delayed response). These changes in subcellular localization could be completely blocked by the free radical scavenger, WR1065. By comparison, two DNA-damaging agents that do not generate free radicals, mitomycin C and doxorubicin, caused translocation only after 12-24 h of exposure to the drugs, and this effect could not be inhibited by WR1065. Hence, although all three DNA-damaging agents induced relocalization of p53 to the nucleus, only the translocation caused by radiation was sensitive to free radical scavenging. We suggest that the free radicals generated by ionizing radiation can signal p53 translocation to the nucleus.

Martinez, J. D.↗
DOE OSTI2025

Resolving the dynamic correlated disorder in KTa 1- x Nb x O 3

Understanding the complex temporal and spatial correlations of ions in disordered perovskite oxides is critical to rationalize their functional properties. Here, in this study, we provide new insights into the longstanding controversy regarding the off-centering of transition metal ions in the archetypal ferroelectric alloy KTa 1-x Nb x O 3 (KTN). By mapping the full energy (E) and wavevector (Q) dependence of the dynamical structure factor S(Q, E) using neutron scattering, and rationalizing our observations with atomistic simulations leveraging machine learning, we fully resolve the static vs dynamic nature of diffuse scattering sheets, as well as their composition (x) and temperature dependence. Our first-principles simulations, extended with machine-learning molecular dynamics, reproduce both inelastic neutron spectra and diffuse features, and establish how dynamically-correlated transition metal off-centerings couple to phonons, unifying local and collective viewpoints. This study sheds new light into an exemplary ferroelectric systems and shows the importance of mapping the full S(Q, E) to reveal critical spatio-temporal correlations of atomic disorder from which functional properties emerge.

42 ENGINEERING↗
DOE OSTI2020

A methodology to compute the critical current limit in Nb3Sn magnets

Numerous experiments have shown that the loads applied to Nb3Sn strands and cables can reduce their critical current. Experiments, performed on uniaxially loaded strands, allowed to define clear laws to describe the evolution of the critical surface as a function of the applied current, field, temperature and strain. It is, however, still unclear how these laws can be applied to superconducting magnets. The present paper proposes a methodology to estimate the critical current and temperature margin reduction on superconducting magnets due to stress on the superconducting material. The methodology is tested on the MQXF magnets, a quadrupole developed for the High Luminosity LHC project, and successfully validated by comparing computed strain with data from strain gauge measurements. Overall, results suggested that, because of the stresses arising in winding during assembly, cool-down and powering, the current limit of the magnet is lower than the expected short sample limit, and that the most critical region does not coincide with the peak field location.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
NASA NTRS1990

SE and I system testability: The key to space system FDIR and verification testing

The key to implementing self-diagnosing design is a systems engineering task focused on design for testability concurrent with design for functionality. The design for testability process described here is the product of several years of DOD study and experience. Its application to the space station has begun on Work Package II under NASA and McDonnell direction. Other work package teams are being briefed by Harris Corporation with the hope of convincing them to embrace the process. For the purpose of this discussion the term testability is used to describe the systems engineering process by which designers can assure themselves and their reviewers that their designs are TESTABLE, that is they will support the downstream process of determining their functionality. Due to the complexity and density of present-day state-of-the-art designs, such as pipeline processors and high-speed integrated circuit technology, testability feature design is a critical requirement of the functional design process. A systematic approach to Space systems test and checkout as well as fault detection fault isolation reconfiguration (FDFIR) will minimize operational costs and maximize operational efficiency. An effective design for the testability program must be implemented by all contractors to insure meeting this objective. The process is well understood and technology is here to support it.

Barry, Thomas↗
NASA NTRS1946

Critical Mach Numbers of Thin Airfoil Sections with Plain Flaps

Critical Mach number as function of lift coefficient is determined for certain moderately thick NACA low-drag airfoils. Results, given graphically, included calculations on same airfoil sections with plain flaps for small flap deflections. Curves indicate optimum critical conditions for airfoils with flaps in such form that they can be compared with corresponding results for zero flap deflections. Plain flaps increase life-coefficient range for which critical Mach number is in region of high values characteristic of low-drag airfoils.

AIRFOILS - NACA 651-208 - CHARACTERISTICS LOW-DRAG↗
DOE OSTI2011

Dynamic Resistance of YBCO-Coated Conductors in Applied AC Fields with DC Transport Currents and DC Background Fields

In order to predict heat loads in future saturable core fault-current-limiting devices due to ac fringing fields, dynamic resistance in YBCO-coated conductors was measured at 77 K in peak ac fields up to 25 mT at 60 Hz and in dc fields up to 1 T. With the sample orientation set such that the conductor face was either parallel or perpendicular to the ac and dc applied fields, the dynamic resistance was measured at different fractions of the critical current to determine the relationship between the dc transport current and the applied fields. With respect to field orientation, the dynamic resistance for ac fields that were perpendicular to the conductor face was significantly higher than when the ac fields were parallel to the conductor face. It was also observed that the dynamic resistance: (1) increased with increasing fraction of the dc transport current to the critical current, (2) was proportional to the inverse of the critical current, and (3) demonstrated a linear dependence with the applied ac field once a threshold field was exceeded. This functional behavior was consistent with a critical state model for the dynamic resistance, but discrepancies in absolute value of the dynamic resistance suggested that further theoretical development is needed.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2016

First-principles study of mechanical properties of zirconium alloys and hydrides

Zirconium alloys have been extensively used as fuel cladding materials in nuclear light water reactors (LWRs) due to their favorable mechanical properties, corrosion resistance, low thermal neutron capture cross section and criticality. Because the main functions of these structural materials are to maintain the integrity of UO{sub 2} fuel rods and prevent the release of fission products into the biosphere, a detailed knowledge of their structural stability is of critical importance to ensure the safe operation of nuclear reactors, and the safety of storage, transportation or disposition of used nuclear fuel assemblies. While the Zr-H phase diagram has been known since the 1950's and has remained largely unchanged, the structures, formation mechanisms, and stability of Zr-hydride phases in pure α-Zr or Zr alloys matrices have been subjects of much debate over the last few decades. The formation of hydride phases in the Zr matrix has been linked in previous studies to the degradation of mechanical properties of Zr/Zr-alloys materials. Therefore, an accurate knowledge of the interplay between the structures, stability and mechanical properties of Zr/Zr-alloys and Zr hydrides is of paramount significance to ensure materials reliability during their in- service lifetime. Despite few first-principles studies have investigated the mechanical stability of Zr hydrides polymorphs proposed so far, no ab initio studies have been carried out, to the best of our knowledge, on the mechanical properties of modern nuclear-grade zirconium alloys such as Zircaloy-4 (Zry-4; 1.2-1.7% Sn), Zirconium low oxidation alloy (ZIRLO; 0.7-1.0% Sn and ∼1.0% Nb), or M5 alloy (0.8-1.2% Nb). Therefore, it is important to carry out a series of first-principles calculations systematically to investigate the structure-property relationship of zirconium hydrides and zirconium alloys, that can help explain differences in elastic properties between high-purity zirconium and nuclear-grade zirconium alloys. (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2017

Proof Of Concept of Integrated Load Measurement in 3D Printed Structures

Currently, research on structural health monitoring systems is focused on direct integration of the system into a component or structure. The latter results in a so-called smart structure. One example of a smart structure is a component with integrated strain sensing for continuous load monitoring. Additive manufacturing, or 3D printing, now also enables such integration of functions inside components. As a proof-of-concept, the Fused Deposition Modeling (FDM) technique was used to integrate a strain sensing element inside polymer (ABS) tensile test samples. The strain sensing element consisted of a closed capillary filled with a fluid and connected to an externally mounted pressure sensor. The volumetric deformation of the integrated capillary resulted in pressure changes in the fluid. The obtained pressure measurements during tensile testing are reported in this paper and compared to state-of-the-art extensometer measurements. The sensitivity of the 3D printed pressure-based strain sensor is primarily a function of the compressibility of the capillary fluid. Air- and watertightness are of critical importance for the proper functioning of the 3D printed pressure-based strain sensor. Therefore, the best after-treatment procedure was selected on basis of a comparative analysis. The obtained pressure measurements are linear with respect to the extensometer readings, and the uncertainty on the strain measurement of a capillary filled with water (incompressible fluid) is ±3.1 µstrain, which is approximately three times less sensitive than conventional strain gauges (±1 µstrain), but 32 times more sensitive than the same sensor based on air (compressible fluid) (±101 µstrain).

42 ENGINEERING↗