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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS1988

Multi-point measurements of ULF wave phases using a multi-channel energetic ion detector

The oscillation of differential fluxes of energetic ions modulated by a ULF wave often shows a phase shift between measurements in back-to-back detectors with look directions perpendicular to the ambient magnetic field. In a plasma of a single ion species, the phase difference is caused by displacement of the effective measurement positions by one ion gyroradius to each side of the detector. As the wave phase is periodic, the observed phase shift can correspond to a family of possible wavelengths. Simultaneous measurements of the flux modulations in different energy channels, which are equivalent to measurements of the wave phase at different positions, may make it possible to single out a unique wavelength consistent with all the measurements. Using the medium-energy-particle experiments ISEE-1 and 2, each of which may serve as a back-to-back detector, the above method was applied to a compressional Pc 5 wave observed near the equatorial plane at L between about 7 and 11. The transverse propagation properties of the wave were determined unambiguously.

Lin, N.↗
DOE OSTI2021

A heavy-ion production channel of 149 Tb via 63 Cu bombardment of 89 Y

We report the radionuclide 149 Tb (t 1/2 = 4.1 h) is a potential theranostic isotope which can simultaneously be used for targeted-alpha-particle therapy and positron-emission tomography. Feasibility experiments were performed to test a near-symmetric heavy-ion reaction of 63 Cu bombardment on monoisotopic 89 Y. The indirect reaction was studied to avoid isomer production. Offline gamma spectroscopy was used to quantify thick-target physical yields and experimental results show modest agreement to the fusion-evaporation code PACE4. A near-symmetric fission yield was also observed.

149Tb↗
NASA NTRS2017

Flexible Proteins at the Origin of Life

Almost all modern proteins possess well-defined, relatively rigid scaffolds that provide structural preorganization for desired functions. Such scaffolds require the sufficient length of a polypeptide chain and extensive evolutionary optimization. How ancestral proteins attained functionality, even though they were most likely markedly smaller than their contemporary descendants, remains a major, unresolved question in the origin of life. On the basis of evidence from experiments and computer simulations, we argue that at least some of the earliest water-soluble and membrane proteins were markedly more flexible than their modern counterparts. As an example, we consider a small, evolved in vitro ligase, based on a novel architecture that may be the archetype of primordial enzymes. The protein does not contain a hydrophobic core or conventional elements of the secondary structure characteristic of modern water-soluble proteins, but instead is built of a flexible, catalytic loop supported by a small hydrophilic core containing zinc atoms. It appears that disorder in the polypeptide chain imparts robustness to mutations in the protein core. Simple ion channels, likely the earliest membrane protein assemblies, could also be quite flexible, but still retain their functionality, again in contrast to their modern descendants. This is demonstrated in the example of antiamoebin, which can serve as a useful model of small peptides forming ancestral ion channels. Common features of the earliest, functional protein architectures discussed here include not only their flexibility, but also a low level of evolutionary optimization and heterogeneity in amino acid composition and, possibly, the type of peptide bonds in the protein backbone.

Flexible protein↗
DOE OSTI2022

Selective posttranslational inhibition of Ca V β 1 -associated voltage-dependent calcium channels with a functionalized nanobody

Ca 2+ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca 2+ influx, to mediate disparate functions is diversity of HVACC pore-forming α1 and auxiliary Ca V β 1 –Ca V β 4 subunits. Selective Ca V α 1 blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on Ca V β isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of Ca V β isoforms. Here, we identify a nanobody (nb.E8) that selectively binds Ca V β 1 SH3 domain and inhibits Ca V β 1 -associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through Ca V β 1 -reconstituted Ca V 1/Ca V 2 and native Ca V 1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca 2+ influx and excitation-transcription coupling in hippocampal neurons, but was inert against Ca V β 2 -associated Ca V 1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of Ca V β 1 signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A method to predict texture effect on ion beam channeling analysis of polycrystals and the application to study the mosaic spreading effect in highly oriented pyrolytic graphite

We propose a method to convert the channeling Rutherford backscattering spectrum yield map of a single crystal to a polycrystal through a matrix rotation technique. The rotation matrix is determined by the deviation of the crystal axial direction from the original z axis. The final yield map is created after averaging the rotated yields using the texture function as the weight factor. For highly oriented pyrolytic graphite (HOPG) exhibiting mosaic spread, the method leads to a Gaussian kernel averaging of the map obtained from a single crystal. The yield map of a single crystal is obtained by a simulation of ion trajectories in a potential field described by Moliere screened Coulomb potentials. Yield maps are calculated under various σ values (standard deviations of mosaic spread). The simulated results are compared with experimental results obtained using 1.2 MeV alpha particle. σ is extracted through the best fitting, demonstrating that the method can be used to obtain texture details. The effects of mosaic spread on minimum yield χ min and the half-width at half maximum of angular scans ψ ½ are systematically modeled and compared with previous theoretical equations. The study also shows that previous theoretical equations are valid only at small σ values. The proposed method can be applied to any type of polycrystal and is not limited to HOPG. It provides near-surface mosaic spread and crystallography information with a longitudinal depth resolution of tens of nanometers and is not influenced by grain shapes.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2023

Recent progress on understanding the temperature-dependent irradiation resistance ranking among NiFe, NiCoCr, and NiCoFeCr alloys: A review

Systematic temperature-effects investigations on damage evolution in ion-irradiated Ni-based concentrated solid-solution alloys (CSAs) are pivotal to provide reliance on their use in nuclear applications. Here, in search of the origin behind the temperature-dependent irradiation resistance ranking among equiatomic NiFe, NiCoCr and NiCoFeCr alloys, we have compared, previously experimental and theoretical published data involving ion irradiation experiments performed on these alloys with new ion channeling results from ion-irradiated NiCoFeCr at 500 K. Moreover, the current results are compared with independent theoretical calculations and relevant TEM results from literature, which allow us to suggest that the lower migration energy of vacancies in NiCoCr, as compared with those in NiFe and NiCoFeCr, is the reason behind why NiCoCr is no longer outperforming NiFe under ion irradiation above 300 K.

99 GENERAL AND MISCELLANEOUS↗
NASA NTRS1992

Mechanism of blue-light-induced plasma-membrane depolarization in etiolated cucumber hypocotyls

A large, transient depolarization of the plasma membrane precedes the rapid blue-light (BL)-induced growth suppression in etiolated seedlings of Cucumis sativus L. The mechanism of this voltage transient was investigated by applying inhibitors of ion channels and the plasma-membrane H(+)-ATPase, by manipulating extracellular ion concentrations, and by measuring cell input resistance and ATP levels. The depolarizing phase was not affected by Ca(2+)-channel blockers (verapamil, La3+) or by reducing extracellular free Ca2+ by treatment with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). However, these treatments did reduce the rate of repolarization, indicating an inward movement of Ca2+ is involved. No effects of the K(+)-channel blocker tetraethylammonium (TEA+) were detected. Vanadate and KCN, used to inhibit the H(+)-ATPase, reduced or completely inhibited the BL-induced depolarization. Levels of ATP increased by 11-26% after 1-2 min of BL. Input resistance of trichrome cells, measured with double-barreled microelectrodes, remained constant during the onset of the depolarization but decreased as the membrane voltage became more positive than -90 mV. The results indicate that the depolarization mechanism initially involves inactivation of the H(+)-ATPase with subsequent transient activation of one or more types of ion channels.

NASA Program Space Biology↗
DOE OSTI2024

Kainate receptor channel opening and gating mechanism

Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Therapeutic targeting of membrane-associated proteins in central nervous system tumors

The activity of the most complex system, the central nervous system (CNS) is profoundly regulated by a huge number of membrane-associated proteins (MAP). A minor change stimulates immense chemical changes and the elicited response is organized by MAP, which acts as a receptor of that chemical or channel enabling the flow of ions. Slight changes in the activity or expression of these MAPs lead to severe consequences such as cognitive disorders, memory loss, or cancer. CNS tumors are heterogeneous in nature and hard-to-treat due to random mutations in MAPs; like as overexpression of EGFRvIII/TGFβR/VEGFR, change in adhesion molecules α5β3 integrin/SEMA3A, imbalance in ion channel proteins, etc. Extensive research is under process for developing new therapeutic approaches using these proteins such as targeted cytotoxic radiotherapy, drug-delivery, and prodrug activation, blocking of receptors like GluA1, developing viral vector against cell surface receptor. The combinatorial approach of these strategies along with the conventional one might be more potential. Henceforth, our review focuses on in-depth analysis regarding MAPs aiming for a better understanding for developing an efficient therapeutic approach for targeting CNS tumors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

In situ potassium and hydrogen ion exchange into a cubic zirconium silicate microporous material

The selective separation of ions from aqueous systems, and even in the human body, is a crucial to overall environmental management and health. Nanoporous materials are widely known for their selective removal of cations from aqueous media, and therefore have been targeted for use as a pharmaceutical to treat hyperkalemia. This study investigated the detailed crystallographic molecular mechanisms that control the potassium ion selectivity in the nanoporous cubic zirconium silicate (CZS) related materials. Using time-resolved in situ Raman spectroscopy and time-resolved in situ X-ray diffraction, the selectivity mechanisms were determined to involve a synchronous cation-cation repulsion process that serves to open a favorable coordination bonding environment for potassium, not unlike the ion selectivity filter process found in potassium ion channels in proteins. Enhancement of ion exchange was observed when the CZS material was in a partial protonated state (≈3:1 Na:H), causing an expansion of the unit-cell volume, enlargement of the 7 member-ring window, and distortion of framework polyhedra, which allowed increased accessibility to the cage structures and resulted in rapid irreversible potassium ion exchange.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2000

Extracellular calcium-sensing-receptor (CaR)-mediated opening of an outward K(+) channel in murine MC3T3-E1 osteoblastic cells: evidence for expression of a functional CaR

The existence in osteoblasts of the G-protein-coupled extracellular calcium (Ca(o)(2+))-sensing receptor (CaR) that was originally cloned from parathyroid and kidney remains controversial. In our recent studies, we utilized multiple detection methods to demonstrate the expression of CaR transcripts and protein in several osteoblastic cell lines, including murine MC3T3-E1 cells. Although we and others have shown that high Ca(o)(2+) and other polycationic CaR agonists modulate the function of MC3T3-E1 cells, none of these actions has been unequivocally shown to be mediated by the CaR. Previous investigations using neurons and lens epithelial cells have shown that activation of the CaR stimulates Ca(2+)-activated K(+) channels. Because osteoblastic cells express a similar type of channel, we have examined the effects of specific "calcimimetic" CaR activators on the activity of a Ca(2+)-activated K(+) channel in MC3T3-E1 cells as a way of showing that the CaR is not only expressed in those cells but is functionally active. Patch-clamp analysis in the cell-attached mode showed that raising Ca(o)(2+) from 0.75 to 2.75 mmol/L elicited about a fourfold increase in the open state probability (P(o)) of an outward K(+) channel with a conductance of approximately 92 pS. The selective calcimimetic CaR activator, NPS R-467 (0.5 micromol/L), evoked a similar activation of the channel, while its less active stereoisomer, NPSS-467 (0.5 micromol/L), did not. Thus, the CaR is not only expressed in MC3T3-E1 cells, but is also functionally coupled to the activity of a Ca(2+)-activated K(+) channel. This receptor, therefore, could transduce local or systemic changes in Ca(o)(2+) into changes in the activity of this ion channel and related physiological processes in these and perhaps other osteoblastic cells.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

Contemplating the plasmalemmal control center model

An abundant epidermal mechanosensory calcium-selective ion channel appears able not only to detect mechanical stimuli such as those that initiate gravitropism but also to detect thermal, electrical, and various chemical stimuli. Because it responds to multimodal input with a second messenger output, this channel system seems likely to be an integrator that can engage in feedbacks with many other systems of the cell--and feedback is the hallmark of regulation. In general, the mechanical tension required for channel activation is likely transmitted from the relatively rigid cell wall to the plasma membrane system via linkage or adhesion sites that display antigenicities recognized by antibodies to animal beta-1 integrin, vitronectin, and fibronectin and which have mechanical connections to the cytoskeleton. Thus, functionally, leverage exerted against any given adhesion site will tend to control channels within a surrounding domain. Reactions initiated by passage of calcium ions through the channels could presumably be more effectively regulated if channels within the domains were somewhat clustered and if appropriate receptors, kinases, porters, pumps, and some key cytoskeletal anchoring sites were in turn clustered about them. Accumulating evidence suggests not only that activity of clusters of channels may contribute to control of cytoskeletal architecture and of regulatory protein function within their domain, but also that both a variety of regulatory proteins and components of the cortical cytoskeleton may contribute to control of channel activity. The emerging capabilities of electronic optical microscopy are well suited for resolving the spatial distributions of many of these cytoskeletal and regulatory molecules in living cells, and for following some of their behaviors as channels are stimulated to open and cytosolic calcium builds in their vicinity. Such microscopy, coupled with biochemical and physiological probing, should help to establish the nature of the feedback loops putatively controlled by the linkage sites and their channel domains.

Review↗
NASA NTRS2009

Emergence of Complexity in Protein Functions and Metabolic Networks

In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis of very large libraries of random amino acid sequences and subsequently subjecting them to in vitro evolution. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions, important clues have been uncovered. Considerable progress has been also achieved in understanding the origins of membrane proteins. We will address this issue in the example of ion channels - proteins that mediate transport of ions across cell walls. Remarkably, despite overall complexity of these proteins in contemporary cells, their structural motifs are quite simple, with -helices being most common. By combining results of experimental and computer simulation studies on synthetic models and simple, natural channels, I will show that, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Pohorille, Andzej↗
DOE OSTI2026

Modeling Temperature Profiles in the Pedestal of NSTX with Reduced Models

This paper describes new modeling capabilities for predicting H-mode pedestal profiles in spherical tokamaks. Temperature profiles for NSTX discharges 132543 and 132588 are modeled by coupling the \textsc{astra} transport solver with neoclassical transport and gyrokinetic-based reduced models for electron temperature gradient (ETG) and kinetic ballooning mode (KBM) instabilities. A quasi-linear surrogate model for ion-scale transport is developed using linear \textsc{gene} simulations, requiring only a single free parameter calibrated to one discharge. Time-evolving the temperatures with fixed density yields good agreement with experiments for both discharges. Systematic analysis of the transport mechanisms reveals that neoclassical transport is huge across the entire pedestal region for the ion channel. ETG turbulence is large in the plasma edge and low density gradient region, contributing substantially to the electron channel. However, KBM/MHD-like modes also drive significant transport in both the ion and electron thermal channels, making them essential for accurate pedestal modeling. Further refinements, including explicit E×B shear suppression and scaled ETG transport, produce quantitative but not qualitative improvements. This work lays the foundation for predictive modeling of future devices. This paper is on arxiv and has been submitted to Nuclear Fusion.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2023

Cryo-EM structures reveal native GABA A receptor assemblies and pharmacology

Type A γ-aminobutyric acid receptors (GABA A Rs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants. However, our understanding of GABA A R pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABA A R assemblies containing the widely expressed α1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron microscopy (cryo-EM) analysis and single-molecule photobleaching experiments, we uncover three major structural populations in the brain: the canonical α1β2γ2 receptor containing two α1 subunits, and two assemblies containing one α1 and either an α2 or α3 subunit, in which the single α1-containing receptors feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, APG is bound at the transmembrane α/β subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABA A Rs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify the ion channel pore and the binding sites for GABA and insomnia medications. Our data reveal the major α1-containing GABA A R assemblies, bound with endogenous neurosteroid, thus defining a structural landscape from which subtype-specific drugs can be developed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Structural insights into GABA A receptor potentiation by Quaalude

Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a notorious recreational drug in the 1960s-80s. Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance. Methaqualone principally targets GABA A receptors, which are the major inhibitory neurotransmitter-gated ion channels in the brain. The restricted status and limited accessibility of methaqualone have contributed to its pharmacology being understudied. Here, we use cryo-EM to localize the GABA A receptor binding sites of methaqualone and its more potent derivative, PPTQ, to the same intersubunit transmembrane sites targeted by the general anesthetics propofol and etomidate. Both methaqualone and PPTQ insert more deeply into subunit interfaces than the previously-characterized modulators. Binding of quinazolinones to this site results in widening of the extracellular half of the ion-conducting pore, following a trend among positive allosteric modulators in destabilizing the hydrophobic activation gate in the pore as a mechanism for receptor potentiation. These insights shed light on the underexplored pharmacology of quinazolinones and further elucidate the molecular mechanisms of allosteric GABA A receptor modulation through transmembrane binding sites.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Structural and dynamic mechanisms of GABA A receptor modulators with opposing activities

γ-Aminobutyric acid type A (GABA A ) receptors are pentameric ligand-gated ion channels abundant in the central nervous system and are prolific drug targets for treating anxiety, sleep disorders and epilepsy. Diverse small molecules exert a spectrum of effects on γ-aminobutyric acid type A (GABA A ) receptors by acting at the classical benzodiazepine site. They can potentiate the response to GABA, attenuate channel activity, or counteract modulation by other ligands. Structural mechanisms underlying the actions of these drugs are not fully understood. Here we present two high-resolution structures of GABA A receptors in complex with zolpidem, a positive allosteric modulator and heavily prescribed hypnotic, and DMCM, a negative allosteric modulator with convulsant and anxiogenic properties. These two drugs share the extracellular benzodiazepine site at the α/γ subunit interface and two transmembrane sites at β/α interfaces. Structural analyses reveal a basis for the subtype selectivity of zolpidem that underlies its clinical success. Molecular dynamics simulations provide insight into how DMCM switches from a negative to a positive modulator as a function of binding site occupancy. Together, these findings expand our understanding of how GABA A receptor allosteric modulators acting through a common site can have diverging activities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Unveiling Swift Heavy Ion Track Morphology in Sr-Based High-Entropy Perovskites

The incorporation of multiple cations on a single lattice site in the high-entropy oxides is considered the key driving factor for modifying the known atomic-level response to energetic ion irradiation due to the presence of structural disorder; however, these effects are not well-understood yet. In this work, we present atomic-level insight into irradiation-induced nanoscale phase transformations in a perovskite-structured high-entropy oxide, Sr(Zr 0.2 Sn 0.2 Ti 0.2 Hf 0.2 Nb 0.2 )O 3 (Sr(HE)O 3 ), subjected to 774 MeV swift Xe heavy ions, where damage is dominated by inelastic ion−lattice interactions. While these ions generally are known to create nanoscale disordered channels, “ion tracks”, along the penetration direction in the material, this study shows the formation of discontinuous and partially recrystallized ion tracks in Sr(HE)O 3 . Compared to SrTiO 3 irradiated under identical energy loss conditions, the ion tracks in Sr(HE)O 3 exhibit significantly reduced diameters and a markedly different interfacial structure. Notably, the crystalline−amorphous interface in Sr(HE)O 3 shows minimal lattice distortion, confined to approximately 2−3 monolayers, in contrast to the extended disordered shell commonly observed in SrTiO 3 . Using in situ atomic-resolution electron microscopy, we further demonstrate that the amorphous/disordered regions within Sr(HE)O 3 ion tracks remain highly stable under electron irradiation, whereas tracks in SrTiO 3 readily recrystallize. This enhanced stability is attributed to the dominance of structural and chemical complexity arising from multiple B-site cations, which suppress defect migration and templated recrystallization driven by electronic excitations and local heating. Overall, this study highlights how high-entropy oxide chemistry fundamentally reshapes irradiation damage evolution, offering insights into defect formation and phase stability under extreme conditions.

36 MATERIALS SCIENCE↗