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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 397 records · Page 22
All sourcesNASA NTRSDOE OSTI
NASA NTRS1991

Characterization of Asymmetry in Magnetoacoustic Emission Burst by Numerical Processes

It has been well known that the pattern of the magnetoacoustic emission (MAE) burst observed during the sweep over one half-cycle of the hysteresis loop becomes asymmetric depending on the strength of the magnetic domain wall-defect interaction and the state of residual stresses in a ferromagnet. The ascending asymmetry due to the former has been observed at a very low frequency (.7 Hz) of applied AC magnetic field at a given amplitude. The descending asymmetry due to uniaxial compressive stress has been typically observed at the AC applied magnetic field frequency of 20 Hz. The physical interpretation of both types of asymmetry has been well established. It is, however, necessary to perform investigations of the dependence of asymmetry on externally controlled parameters such as the amplitude and frequency of the AC applied magnetic fields. The purpose of the present study is therefore to devise a mathematical means that describes the degree of asymmetry of the MAE burst and apply this scheme to investigate the AC magnetic field amplitude dependence of the asymmetry.

Namkung, M.↗
DOE OSTI2011

Structure and design of the electron lens for RHIC

Two electron lenses for a head-on beam-beam compensation are being planned for RHIC; one for each circulating proton beam. The transverse profile of the electron beam will be Gaussian up to a maximum radius of r{sub e} = 3{sigma}. Simulations and design of the electron gun with Gaussian radial emission current density profile and of the electron collector are presented. Ions of the residual gas generated in the interaction region by electron and proton beams will be removed by an axial gradient of the electric field towards the electron collector. A method for the optical observation of the transverse profile of the electron beam is described.

43 PARTICLE ACCELERATORS↗
DOE OSTI2011

Genomic and Expression Analyses of Cold-Adapted Microorganisms.

Contents 7.1 Introduction 7.2 Ecological evidence of bacterial adaptation to cold 7.2.1 Characteristics of cold environments and implications for microbial ecology 7.2.2 Ecological adaptation in Exiguobacterium spp. and Psychrobacter spp. 7.3 Gene Expression Responses to the Cold 7.3.1 Fundamentals of Gene Expression Responses to Cold 7.3.2 Acclimation for Life in Cold Habitats 7.3.2.1 Translation and Chaperone Proteins: Safeguarding the functional units of cellular physiology 7.3.2.2 Carbon and Energy metabolism: resource efficiency over long generation times 7.3.2.3 Amino Acid Biosynthesis: Species-specific responses to species-specific deficiencies 7.3.2.4 Compatible solutes: a concomitant response in cryoenvironments 7.3.2.5 Membrane fluidity: A major role in the overall metabolic rate at temperature 7.3.2.6 The cell wall at low temperature: A poorly understood growth rate determinant 7.3.2.7 Transporters: The balance between local nutrient uptake and depletion 7.3.2.8 Genome plasticity. The potential role of transposases and repeated sequences. 7.4 Protein adaptations to cold 7.4.1 The low temperature challenge 7.4.2 The stability activity relationship 7.4.3 Structural features of cold adapted enzymes. 7.4.4 Hydrophobic interactions 7.4.5 Electrostatic interactions 7.4.5.1 Arginine 7.4.5.2 Acidic residues 7.4.6 Structural elements 7.4.6.1 -helices and -sheets 7.4.6.2 Proline and Glycine 7.4.6.3 Disordered regions 7.5 Comparison of cold- and warm-adapted Exiguobacterium strains 7.5.1 Phylogeny reflects adaptations to environmental conditions 7.5.2 Genomic comparison of two strains 7.6 Summary and future directions

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

On the Life Expectance of High-power CW Magnetrons for SRF Accelerators

Modern CW or pulse Superconducting RF (SRF) accelerators require efficient RF sources controllable in phase and power with a reduced cost. Therefore, utilization of the high-power CW magnetrons as RF sources in SRF accelerator projects was proposed in a number of works, e.g., [1, 2]. But typically, the CW magnetrons are designed as RF sources for industrial heating, and the lifetime of the tubes is not the first priority as it is required for high-energy accelerators. The high-power industrial CW magnetrons use the cathodes made of pure tungsten. The emission properties of the tungsten cathodes are not deteriorated much by electron and ion bombardments, but the latter causes sputtering of the cathode in the magnetron crossed fields. The sputtered cathode material covers the magnetron interior. This leads to sparks and discharges that limit the life of the magnetrons. We considered an analysis of magnetron failure modes vs. output power [3]. We developed a model of ionization of the residual gas in the magnetrons interaction space and simulated the spattering of the cathode in 100 kW CW magnetrons to estimate the life expectancy. Basing on results we proposed ways to increase the CW magnetrons longevity for SRF accelerators.

43 PARTICLE ACCELERATORS↗
DOE OSTI2025

Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine

RAS is the most frequently mutated oncogene in cancer. RAS proteins show high sequence similarities in their G-domains but are significantly different in their C-terminal hypervariable regions (HVR). These regions interact with the cell membrane via lipid anchors that result from posttranslational modifications (PTM) of cysteine residues. KRAS4b is unique as it has only one cysteine that undergoes PTM, C185. Small molecule covalent modification of C185 would block any form of prenylation and subsequently inhibit attachment of KRAS4b to the cell membrane, blocking its biological activity. We translated this concept to the discovery and development of disulfide tethering screen hits into irreversible covalent modifiers of C185. These compounds inhibited proliferation of KRAS4b-driven mouse embryonic fibroblasts, but not cells driven by N-myristoylated KRAS4b that harbor a C185S mutation and are not dependent on C185 prenylation. Top–down proteomics was used to confirm target engagement in cells. These compounds bind in a pocket formed when the HVR folds back between helix 3 and 4 in the G-domain (HVR-α3-α4). This interaction can happen in the absence of small molecules as predicted by molecular dynamics simulations and is stabilized in the presence of C185 binders as confirmed by small-angle X-ray scattering and solution NMR. NOESY-HSQC, an NMR approach that measures internuclear distances of 6 Å or less, and structure analysis identified the critical residues and interactions that define the HVR-α3-α4 pocket. Further development of compounds that bind to this pocket could be the basis of a new approach to targeting KRAS cancers.

C185↗
DOE OSTI2018

Crystal structures of the human 4-1BB receptor bound to its ligand 4-1BBL reveal covalent receptor dimerization as a potential signaling amplifier

Human (h)4-1BB (TNFRSF9 or CD137) is an inducible tumor necrosis factor receptor (TNFR) superfamily member that interacts with its cognate ligand h4-1BBL to promote T lymphocyte activation and proliferation. h4-1BB is currently being targeted with agonists in cancer immunotherapy. Here, we determined the crystal structures of unbound h4-1BBL and both WT h4-1BB and a dimerization-deficient h4-1BB mutant (C121S) in complex with h4-1BBL at resolutions between 2.7 and 3.2 Å. Here, we observed that the structural arrangement of 4-1BBL, both unbound and in the complex, represents the canonical bell shape as seen in other similar TNF proteins and differs from the previously reported three-bladed propeller structure of 4-1BBL. We also found that the binding site for the receptor is at the crevice formed between two protomers of h4-1BBL, but that h4-1BB interacts predominantly with only one ligand protomer. Moreover, h4-1BBL lacked the conserved tyrosine residue in the DE loop that forms canonical interactions between other TNFR family molecules and their ligands, suggesting h4-1BBL engages h4-1BB through a distinct mechanism. Of note, we discovered that h4-1BB forms a disulfide-linked dimer because of the presence of an additional cysteine residue found in its cysteine-rich domain 4 (CRD4). As a result, h4-1BB dimerization, in addition to trimerization via h4-1BBL binding, could result in cross-linking of individual ligand–receptor complexes to form a 2D network that stimulates strong h4-1BB signaling. Finally, this work provides critical insights into the structural and functional properties of both h4-1BB and h4-1BBL and reveals that covalent receptor dimerization amplifies h4-1BB signaling.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Channelrhodopsin-2 Function is Modulated by Residual Hydrophobic Mismatch with the Surrounding Lipid Environment

Channelrhodopsin-2 (ChR2) is a light-gated ion channel that conducts cations of multiple valencies down the electrochemical gradient. This light-gated property has made ChR2 a popular tool in the field of optogenetics, allowing for the spatial and temporal control of excitable cells with light. A central aspect of protein function is the interaction with the surrounding lipid environment. To further explore these membrane-protein interactions, we demonstrate the role of residual hydrophobic mismatch (RHM) as a mechanistically important component of ChR2 function. We combined computational and functional experiments to understand how RHM between the lipid environment and ChR2 alters the structural and biophysical properties of the channel. Analysis of our results revealed significant RHM at the intracellular/lipid interface of ChR2 from a triad of residues. The resulting energy penalty is substantial and can be lowered via mutagenesis to evaluate the functional effects of this change in lipid-protein interaction energy. The experimental measurement of channel stability, conductance and selectivity resulting from the reduction of the RHM energy penalty showed changes in progressive H+ permeability, kinetics and open-state stability, suggesting how the modulation of ChR2 by the surrounding lipid membrane can play an important biological role and contribute to the design of targeted optogenetic constructs for specific cell types.

Richards, Ryan↗
DOE OSTI2017

An Electrospray Ionization Mass Spectrometry Study on the “In Vacuo” Hetero-Oligomers Formed by the Antimicrobial Peptides, Surfactin and Gramicidin S

It was previously observed that the lipopeptide surfactants in surfactin (Srf) have an antagonistic action towards the highly potent antimicrobial cyclodecapeptide, gramicidin S (GS). This study reports on some of the molecular aspects of the antagonism as investigated through complementary electrospray ionization mass spectrometry techniques. We were able to detect stable 1:1 and 2:1 hetero-oligomers in a mixture of surfactin and gramicidin S. The noncovalent interaction between GS and Srf, with the proposed equilibrium: GS~Srf↔GS+Srf correlated to apparent K{sub d} values of 6–9 μM in gas-phase and 1 μM in aqueous solution. The apparent K{sub d} values decreased with a longer incubation time and indicated a slow oligomerization equilibrium. Furthermore, the low μM K{sub d}{sup app} values of GS~Srf↔GS+Srf fell within the biological concentration range and related to the 2- to 3-fold increase in [GS] needed for bacterial growth inhibition in the presence of Srf. Competition studies indicated that neither Na{sup +} nor Ca{sup 2+} had a major effect on the stability of preformed heterodimers and that GS in fact out-competed Ca{sup 2+} and Na{sup +} from Srf. Traveling wave ion mobility mass spectrometry revealed near symmetrical peaks of the heterodimers correlating to a compact dimer conformation that depend on specific interactions. Collision-induced dissociation studies indicated that the peptide interaction is most probably between one Orn residue in GS and the Asp residue, but not the Glu residue in Srf. We propose that flanking hydrophobic residues in both peptides stabilize the antagonistic and inactive peptide hetero-oligomers and shield the specific polar interactions in an aqueous environment. .

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Engineering a Cysteine-Free Form of Human Fibroblast Growth Factor-1 for “Second Generation” Therapeutic Application

Human fibroblast growth factor-1 (FGF-1) has broad therapeutic potential in regenerative medicine but has undesirable biophysical properties of low thermostability and 3 buried cysteine (Cys) residues (at positions 16, 83, and 117) that interact to promote irreversible protein unfolding under oxidizing conditions. Mutational substitution of such Cys residues eliminates reactive buried thiols but cannot be accomplished simultaneously at all 3 positions without also introducing further substantial instability. The mutational introduction of a novel Cys residue (Ala66Cys) that forms a stabilizing disulfide bond (i.e., cystine) with one of the extant Cys residues (Cys83) effectively eliminates one Cys while increasing overall stability. This increase in stability offsets the associated instability of remaining Cys substitution mutations and permits production of a Cys-free form of FGF-1 (Cys16Ser/Ala66Cys/Cys117Ala) with only minor overall instability. The addition of a further stabilizing mutation (Pro134Ala) creates a Cys-free FGF-1 mutant with essentially wild-type biophysical properties. The elimination of buried free thiols in FGF-1 can substantially increase the protein half-life in cell culture. In this work, we show that the effective cell survival/mitogenic functional activity of a fully Cys-free form is also substantially increased and is equivalent to wild-type FGF-1 formulated in the presence of heparin sulfate as a stabilizing agent. The results identify this Cys-free FGF-1 mutant as an advantageous “second generation” form of FGF-1 for therapeutic application.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1996

Positive selection moments identify potential functional residues in human olfactory receptors

Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

Non-NASA Center↗
DOE OSTI2026

Single pion production and pion propagation in A chilles

We extend the applicability of A chilles (A CHIcagoLand Lepton Event Simulator) by incorporating the single pion production mechanism in a fully exclusive fashion. The electroweak interaction vertex is modeled by combining the state-of-the-art dynamical coupled-channels approach with realistic hole spectral functions, which account for correlations in both the initial target state and the residual spectator system. Final-state interactions are treated using a semiclassical intranuclear cascade that leverages nuclear configurations to determine the correlated spatial distribution of protons and neutrons. The meson-baryon scattering amplitudes used in the cascade are computed within the dynamical coupled-channels framework, consistent with the electroweak vertex. To model pion absorption, we employ the optical potential approach of Oset and Salcedo [Nucl. Phys. A484, 557 (1988).]. As an alternative approach, we explicitly model the production and propagation of resonances which mediate pion-nucleon scattering and pion absorption. We validate our approach against pion-nucleon and pion-nucleus scattering data, and present comparisons with electron- and neutrino-nucleus measurements from e⁢4⁢𝜈, T2K, MINER⁢𝜈⁢A, and MicroBooNE.

Isaacson, Joshua [Michigan State Univ., East Lansi↗
DOE OSTI2018

Enhanced PKMT-substrate recognition through non active-site interactions

Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine residues on many different cellular proteins. Despite extensive biochemical and structural studies, focusing on PKMT active site-peptide interactions, little is known regarding how PKMTs recognize globular substrates. To examine whether these enzymes recognize protein substrates through interactions that take place outside of the active site, we have measured SETD6 and SETD7 activity with both protein and peptide RelA substrate. We have utilized the MTase-Glo™ methyltransferase assay to measure the activity of SETD6 and SETD7 with the different RelA substrates and calculated the Michaelis-Menten (MM) parameters. We found an up to ∼12-fold increase in K{sub M} of the PKMTs activity with RelA peptide relative to the respective full-length protein, emphasizing the significantly higher PKMT-protein interaction affinity. Examination of SETD6 and SETD7 activity toward the same RelA substrates highlight the similarity in substrate recognition for both PKMTs. Our results show that the interaction affinity of SETD6 and SETD7 with RelA is enhanced through interactions that occur outside of the active site leading to higher catalytic efficiency and specificity. These interactions can significantly vary depending on the PKMT and the specific methylation site on RelA. Overall, our results underline that PKMTs can recognize their substrates through docking interactions that occur out of the active site-peptide region for enhancing their activity and specificity in the cellular environment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Novel insights into the apoptosis mechanism of DNA topoisomerase I inhibitor isoliquiritigenin on HCC tumor cell

The inhibitory effect of DNA topoisomerase (Top I) by isoliquiritigenin(ISO) were investigated and their interaction mechanism was evaluated using methods including UV–vis absorption, fluorescence, coupled with molecular simulation, and using the MTT method of inhibition rate of HCC tumor cell SNU475 proliferation assay, finally, the interaction of ISO with calf thymus DNA was investigated by melting measurements and molecular docking studies. It was found that isoliquiritigenin reversibly inhibited DNA Top I in a competitive manner with the concentrations of ISO resulting in 50% activity lost (IC{sub 50}) were estimated to be 0.178 ± 0.12 mM. Isoliquiritigenin exhibited a strong ability to quench the intrinsic fluorescence of Top I through a static quenching procedure. The positive values of enthalpy change and entropy change suggested that the binding of isoliquiritigenin to Top I was driven mainly by hydrophobic interactions. The molecular docking results revealed isoliquiritigenin actually interacted with the primary amino acid residues on the active site of Top I, and the detection results of fluorescence staining and the inhibitory effect on the growth of HCC SUN475 showed that isoliquiritigenin induced the apoptosis cells increased gradually. The interaction of ISO with DNA can cause the denaturation temperature to be increased, which indicated that the stabilization of the DNA helix was increased in the presence of ISO, which indicated that the results provide strong evidence for intercalative binding of ISO with DNA. - Highlights: • ISO reversibly inhibits TOP I activity in an A dose dependent manner. • Hydrophobic interactions play a major role in ISO–TOP I interaction. • ISO has a high affinity close to the active site pocket of TOP I. • The binding of ISO to DNA induces the stability of the structure of DNA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Comparison between simulated and observed LHC beam backgrounds in the ATLAS experiment at E beam =4 TeV

Results of dedicated Monte Carlo simulations of beam-induced background (BIB) in the ATLAS experiment at the Large Hadron Collider (LHC) are presented and compared with data recorded in 2012. During normal physics operation this background arises mainly from scattering of the 4 TeV protons on residual gas in the beam pipe. Methods of reconstructing the BIB signals in the ATLAS detector, developed and implemented in the simulation chain based on the \textsc{Fluka} Monte Carlo simulation package, are described. The interaction rates are determined from the residual gas pressure distribution in the LHC ring in order to set an absolute scale on the predicted rates of BIB so that they can be compared quantitatively with data. Through these comparisons the origins of the BIB leading to different observables in the ATLAS detectors are analysed. The level of agreement between simulation results and BIB measurements by ATLAS in 2012 demonstrates that a good understanding of the origin of BIB has been reached.

47 OTHER INSTRUMENTATION↗
DOE OSTI2017

BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy: BECN2 CCD Structure and Interaction with ATG14

ATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here, we show that the α-helical, coiled-coil domain (CCD) of BECN2, a recently identified mammalian BECN1 paralog, forms an antiparallel, curved homodimer with seven pairs of nonideal packing interactions, while the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer stabilized by multiple, conserved polar interactions. Compared to BECN1, the BECN2 CCD forms a weaker homodimer, but binds more tightly to the ATG14 CCD. Mutation of nonideal BECN2 interface residues to more ideal pairs improves homodimer self-association and thermal stability. Unlike BECN1, all BECN2 CCD mutants bind ATG14, although more weakly than wild type. Thus, polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. These structure-based mechanistic differences in BECN1 and BECN2 homodimerization and heterodimerization likely dictate competitive ATG14 recruitment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Preliminary Activation Analysis of Accelerator Components and Beam Stops at the NSLS-II

Bremsstrahlung is generated at the accelerator systems of the synchrotron radiation facilities by the radiative interaction of circulating electron beam with the accelerator components and with the residual gas molecules in the vacuum chamber. The photoneutron interaction of bremsstrahlung with the materials leads to the radio activation of the accelerator components through neutron emission and the production of radioisotopes. However this activation interaction is a second order effect because the intermediate process of bremsstrahlung production is involved. The photoneutron interaction takes place above the threshold bremsstrahlung energy of 7-20 MeV and the cross section for these interactions are in millibarns.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Classical Swine Fever Virus p7 Protein Interacts with Host Protein CAMLG and Regulates Calcium Permeability at the Endoplasmic Reticulum

We have previously shown that Classical Swine Fever Virus (CSFV) p7 is an essential nonstructural protein with a viroporin activity, a critical function in the progression of virus infection. We also identified p7 domains and amino acid residues critical for pore formation. Here, we describe how p7 specifically interacts with host protein CAMLG, an integral ER transmembrane protein involved in intracellular calcium release regulation and signal response generation. Detection of interaction as well as the identification of p7 areas mediating interaction with CAMLG was performed by yeast two-hybrid. p7-CAMLG interaction was further confirmed by confocal microscopy in eukaryotic cells, co-expressing both proteins. Mutant forms of p7 having substituted native residues identified as mediating interaction with CAMLG showed a decreased co-localization compared with the native forms of p7. Furthermore, it is shown that native p7, but not the mutated forms of p7 that fail to interact with CAMLG, efficiently mediates calcium permeability in the ER. Interestingly, viruses harboring some of those mutated forms of p7 have been previously shown to have a significantly decreased virulence in swine.

59 BASIC BIOLOGICAL SCIENCES↗