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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Detecting element specific electrons from a single cobalt nanocluster with synchrotron x-ray scanning tunneling microscopy

Here, we use a nanofabricated scanning tunneling microscope tip as a detector to investigate local X-ray induced tunneling and electron emission from a single cobalt nanocluster on a Au(111) surface. The tip-detector is positioned a few angstroms above the nanocluster, and ramping the incident X-ray energy across the Co photoabsorption K-edge enables the detection of element specific electrons. Atomic-scale spatial dependent changes in the X-ray absorption cross section are directly measured by taking the X-ray induced current as a function of X-ray energy. From the measured sample and tip currents, element specific X-ray induced current components can be separated and thereby the corresponding yields for the X-ray induced processes of the single cobalt nanocluster can be determined. The detection of element specific synchrotron X-ray induced electrons of a single nanocluster opens a new avenue for materials characterization on a one particle at-a-time basis.

36 MATERIALS SCIENCE↗
DOE OSTI2012

Structure of human dual-specificity phosphatase 27 at 2.38 Å resolution

There are over 100 genes in the human genome that encode protein tyrosine phosphatases (PTPs) and approximately 60 of these are classified as dual-specificity phosphatases (DUSPs). Although many dual-specificity phosphatases are still not well characterized, novel functions have been discovered for some of them that have led to new insights into a variety of biological processes and the molecular basis for certain diseases. Indeed, as the functions of DUSPs continue to be elucidated, a growing number of them are emerging as potential therapeutic targets for diseases such as cancer, diabetes and inflammatory disorders. Here, the overexpression, purification and structure determination of DUSP27 at 2.38 {angstrom} resolution are presented.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. adiponectin) is high or low relative to its distribution. We have previously shown that the heritability ( h 2 ) of adiposity, lipoproteins, postprandial lipemia, pulmonary function, and coffee and alcohol consumption are quantile-specific. Whether adiponectin heritability is quantile specific remains to be determined. Plasma adiponectin concentrations from 4,182 offspring-parent pairs and 1,662 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (β OP , h 2 = 2 β OP /(1 + r spouse )) and full-sib regression slopes ( β FS , h 2 = {(1 + 8r spouse β FS ) 0.05 -1}/(2r spouse )) were robustly estimated by quantile regression with nonparametric significance assigned from 1,000 bootstrap samples. Quantile-specific h 2 (± SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted adiponectin distribution when estimated from β OP ( P trend = 2.2 × 10 -6 ): 0.30 ± 0.03 at the 10th, 0.33 ± 0.04 at the 25th, 0.43 ± 0.04 at the 50th, 0.55 ± 0.05 at the 75th, and 0.57 ± 0.08 at the 90th percentile, and when estimated from β FS (P trend = 7.6 × 10 -7 ): 0.42 ± 0.03 at the 10th, 0.44 ± 0.04 at the 25th, 0.56 ± 0.05 at the 50th, 0.73 ± 0.08 at the 75th, and 0.79 ± 0.11 at the 90th percentile. Consistent with quantile-dependent expressivity, adiponectin’s: (1) heritability was greater in women in accordance with their higher adiponection concentrations; (2) relationships to ADIPOQ polymorphisms were modified by adiposity in accordance with its adiponectin-lowering effect; (3) response to rosiglitazone was predicted by the 45T> G ADIPOQ polymorphism; (4) difference by ADIPOQ haplotypes increased linearly with increasing postprandial adiponectin concentrations. Adiponectin heritability is quantile dependent, which may explain sex-specific heritability, gene-environment and gene-drug interactions, and postprandial response by haplotypes.

Postprandial↗
DOE OSTI2018

A method for site-specific and cryogenic specimen fabrication of liquid/solid interfaces for atom probe tomography

A site-specific, cryogenic, focused ion beam (FIB) method is presented for the preparation of atom probe tomography (APT) specimens from a frozen liquid/solid interface. As a practical example, the interface between water and a corroded boroaluminosilicate glass has been characterized by APT for the first time. The water/glass interface is preserved throughout specimen preparation by plunge freezing the corroding glass particles with the corrosion solution into slush nitrogen. Site-specific specimen preparation is enabled through a new approach to extract and mount a small volume of material using a cryogenically cooled FIB stage and micromanipulator. The prepared APT specimens are subsequently transferred from the FIB to APT under cryogenic and high-vacuum conditions using a novel FIB/APT transfer shuttle and home-built environmental transfer hub attached to the APT system. Particular focus is given to the technical methods for specimen fabrication under cryogenic conditions. Persistent challenges are discussed in addition to future opportunities for this new specimen preparation method.

cryogenic FIB, atom probe tomography (APT), corros↗
DOE OSTI2011

Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

Caenorhabditis elegans fem-3 binding factor (FBF) is a founding member of the PUMILIO/FBF (PUF) family of mRNA regulatory proteins. It regulates multiple mRNAs critical for stem cell maintenance and germline development. Here, we report crystal structures of FBF in complex with 6 different 9-nt RNA sequences, including elements from 4 natural mRNAs. These structures reveal that FBF binds to conserved bases at positions 1-3 and 7-8. The key specificity determinant of FBF vs. other PUF proteins lies in positions 4-6. In FBF/RNA complexes, these bases stack directly with one another and turn away from the RNA-binding surface. A short region of FBF is sufficient to impart its unique specificity and lies directly opposite the flipped bases. We suggest that this region imposes a flattened curvature on the protein; hence, the requirement for the additional nucleotide. The principles of FBF/RNA recognition suggest a general mechanism by which PUF proteins recognize distinct families of RNAs yet exploit very nearly identical atomic contacts in doing so.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2010

Control of the Orientational Order and Nonlinear Optical Response of the "Push-Pull" Chromophore RuPZn via Specific Incorporation into Densely Packed Monolayer Ensembles of an Amphiphilic Four-Helix Bundle Peptide: Characterization of the Peptide−Chromophore Complexes

'Push-pull' chromophores based on extended π-electron systems have been designed to exhibit exceptionally large molecular hyperpolarizabilities. We have engineered an amphiphilic four-helix bundle peptide to vectorially incorporate such hyperpolarizable chromophores having a metalloporphyrin moiety, with high specificity into the interior core of the bundle. The amphiphilic exterior of the bundle facilitates the formation of densely packed monolayer ensembles of the vectorially oriented peptide-chromophore complexes at the liquid-gas interface. Chemical specificity designed into the ends of the bundle facilitates the subsequent covalent attachment of these monolayer ensembles onto the surface of an inorganic substrate. In this article, we describe the structural characterization of these monolayer ensembles at each stage of their fabrication for one such peptide-chromophore complex designated as AP0-RuPZn. In the accompanying article, we describe the characterization of their macroscopic nonlinear optical properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2011

The P 2 ' residue is a key determinant of mesotrypsin specificity: Engineering a high-affinity inhibitor with anticancer activity

PRSS3/mesotrypsin is an atypical isoform of trypsin, the up-regulation of which has been implicated in promoting tumour progression. Mesotrypsin inhibitors could potentially provide valuable research tools and novel therapeutics, but small-molecule trypsin inhibitors have low affinity and little selectivity, whereas protein trypsin inhibitors bind poorly and are rapidly degraded by mesotrypsin. In the present study, we use mutagenesis of a mesotrypsin substrate, APPI (amyloid precursor protein Kunitz protease inhibitor domain), and of a poor mesotrypsin inhibitor, BPTI (bovine pancreatic trypsin inhibitor), to dissect mesotrypsin specificity at the key P2' position. We find that bulky and charged residues strongly disfavour binding, whereas acidic residues facilitate catalysis. Crystal structures of mesotrypsin complexes with BPTI variants provide structural insights into mesotrypsin specificity and inhibition. Through optimization of the P1 and P2' residues of BPTI, we generate a stable high-affinity mesotrypsin inhibitor with an equilibrium binding constant Ki of 5.9 nM, a >2000-fold improvement in affinity over native BPTI. Using this engineered inhibitor, we demonstrate the efficacy of pharmacological inhibition of mesotrypsin in assays of breast cancer cell malignant growth and pancreatic cancer cell invasion. Although further improvements in inhibitor selectivity will be important before clinical potential can be realized, the results of the present study support the feasibility of engineering protein protease inhibitors of mesotrypsin and highlight their therapeutic potential.

42 ENGINEERING↗
DOE OSTI2015

Mode specific dynamics of the H{sub 2} + CH{sub 3} → H + CH{sub 4} reaction studied using quasi-classical trajectory and eight-dimensional quantum dynamics methods

An eight-dimensional quantum dynamical model is proposed and applied to the title reaction. The reaction probabilities and integral cross sections have been determined for both the ground and excited vibrational states of the two reactants. The results indicate that the H{sub 2} stretching and CH{sub 3} umbrella modes, along with the translational energy, strongly promote the reactivity, while the CH{sub 3} symmetric stretching mode has a negligible effect. The observed mode specificity is confirmed by full-dimensional quasi-classical trajectory calculations. The mode specificity can be interpreted by the recently proposed sudden vector projection model, which attributes the enhancement effects of the reactant modes to their strong couplings with the reaction coordinate at the transition state.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Defect sink characteristics of specific grain boundary types in 304 stainless steels under high dose neutron environments

Radiation induced segregation (RIS) is a well-studied phenomena which occurs in many structurally relevant nuclear materials including austenitic stainless steels. RIS occurs due to solute atoms preferentially coupling to mobile point defect fluxes that migrate and interact with defect sinks. Here, a 304 stainless steel was neutron irradiated up to 47.1 dpa at 320 °C. Investigations into the RIS response at specific grain boundary types were utilized to determine the sink characteristics of different boundary types as a function of irradiation dose. A rate theory model built on the foundation of the modified inverse Kirkendall (MIK) model is proposed and benchmarked to the experimental results. This model, termed the GiMIK model, includes alterations in the boundary conditions based on grain boundary structure and includes expressions for interstitial binding. This investigation, through experiment and modeling, found specific grain boundary structures exhibit unique defect sink characteristics depending on their local structure. Such interactions were found to be consistent across all doses investigated and had larger global implications including precipitation of Ni-Si clusters near different grain boundary types.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2017

Quantitative iTRAQ-based secretome analysis reveals species-specific and temporal shifts in carbon utilization strategies among manganese(II)-oxidizing Ascomycete fungi

Fungi generate a wide range of extracellular hydrolytic and oxidative enzymes and reactive metabolites, collectively known as the secretome, that synergistically drive plant litter decomposition in the environment. While secretome studies of model organisms have greatly expanded our knowledge of these enzymes, few have extended secretome characterization to environmental isolates or directly compared temporal patterns of enzyme utilization among diverse species. Thus, the mechanisms of carbon (C) degradation by many ubiquitous soil fungi remain poorly understood. Here we use a combination of iTRAQ proteomics and custom bioinformatic analyses to compare the protein composition of the secretomes of four manganese(II)-oxidizing Ascomycete fungi over a three-week time course. We demonstrate that although the fungi produce a similar suite of extracellular enzymes, they exhibit striking differences in the regulation of these enzymes among species and over time, revealing species-specific and temporal shifts in C utilization strategies as they degrade the same substrate. Specifically, our findings suggest that Paraconiothyrium sporulosum AP3s5-JAC2a and Alternaria alternata SRC1lrK2f employ sequential enzyme secretion patterns concomitant with decreasing resource availability, Stagonospora sp. SRC1lsM3a preferentially degrades proteinaceous substrate before switching to carbohydrates, and Pyrenochaeta sp. DS3sAY3a utilizes primarily peptidases to aggressively attack carbon sources in a concentrated burst. This work highlights the diversity of operative metabolic strategies among cellulose-degrading Ascomycetes and enhances our understanding of their role in C turnover in the environment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Growth Kinetics and Morphology of Barite Crystals Derived from Face-Specific Growth Rates

Here we investigate the growth kinetics and morphology of barite (BaSO 4 ) crystals by measuring the growth rates of the (001), (210), (010), and (100) surfaces using vertical scanning interferometry. Solutions with saturation indices 1.1, 2.1, and 3.0 without additional electrolyte, in 0.7 M NaCl, or in 1.3 mM SrCl2 are investigated. Face-specific growth rates are inhibited in the SrCl 2 solution relative to a solution without electrolyte, except for (100). Contrarily, growth of all faces is promoted in the NaCl solution. The variation of face-specific rates is solution-specific, which leads to a. change of the crystal morphology and overall growth rate of crystals. The measured face-specific growth rates are used to model the growth of single crystals. Modeled crystals have a morphology and size similar to those grown from solution. Based on the model the time dependence of surface area and growth rates is analyzed. Growth rates change with time due to surface area normalization for small crystals and large growth intervals. By extrapolating rates to crystals with large surfaces areas, time-independent growth rates are 0.783, 2.96, and 0.513 mmol∙m -2 ∙h -1 , for saturation index 2.1 solutions without additional electrolyte, NaCl, and SrCl 2 , respectively.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Ab initio-informed maximum entropy modeling of rovibrational relaxation and state-specific dissociation with application to the O{sub 2} + O system

Quasi-classical trajectory (QCT) calculations are used to study state-specific ro-vibrational energy exchange and dissociation in the O{sub 2} + O system. Atom-diatom collisions with energy between 0.1 and 20 eV are calculated with a double many body expansion potential energy surface by Varandas and Pais [Mol. Phys. 65, 843 (1988)]. Inelastic collisions favor mono-quantum vibrational transitions at translational energies above 1.3 eV although multi-quantum transitions are also important. Post-collision vibrational favoring decreases first exponentially and then linearly as Δv increases. Vibrationally elastic collisions (Δv = 0) favor small ΔJ transitions while vibrationally inelastic collisions have equilibrium post-collision rotational distributions. Dissociation exhibits both vibrational and rotational favoring. New vibrational-translational (VT), vibrational-rotational-translational (VRT) energy exchange, and dissociation models are developed based on QCT observations and maximum entropy considerations. Full set of parameters for state-to-state modeling of oxygen is presented. The VT energy exchange model describes 22 000 state-to-state vibrational cross sections using 11 parameters and reproduces vibrational relaxation rates within 30% in the 2500–20 000 K temperature range. The VRT model captures 80 × 10{sup 6} state-to-state ro-vibrational cross sections using 19 parameters and reproduces vibrational relaxation rates within 60% in the 5000–15 000 K temperature range. The developed dissociation model reproduces state-specific and equilibrium dissociation rates within 25% using just 48 parameters. The maximum entropy framework makes it feasible to upscale ab initio simulation to full nonequilibrium flow calculations.

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

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-L-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

METACLUSTER—an R package for context-specific expression analysis of metabolic gene clusters

Abstract Summary Plants and microbes produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have yet to be elucidated. Some biosynthetic pathways are encoded by enzymes collocated in the chromosome. To facilitate a more comprehensive condition and tissue-specific expression analysis of metabolic gene clusters, we developed METACLUSTER, a probabilistic framework for characterizing metabolic gene clusters using context-specific gene expression information. Availability and implementation METACLUSTER is freely available at https://github.com/mbanf/METACLUSTER. Supplementary information Supplementary data are available at Bioinformatics online.

Biochemistry & Molecular Biology↗
DOE OSTI2016

A microbial sensor for organophosphate hydrolysis exploiting an engineered specificity switch in a transcription factor

A whole-cell biosensor utilizing a transcription factor (TF) is an effective tool for sensitive and selective detection of specialty chemicals or anthropogenic molecules, but requires access to an expanded repertoire of TFs. Using homology modeling and ligand docking for binding pocket identification, assisted by conservative mutations in the pocket, we engineered a novel specificity in an Acinetobacter TF, PobR, to ‘sense’ a chemical p-nitrophenol (pNP) and measured the response via a fluorescent protein reporter expressed from a PobR promoter. Out of 107 variants of PobR, four were active when dosed with pNP, with two mutants showing a specificity switch from the native effector 4-hydroxybenzoate (4HB). One of the mutants, pNPmut1 was then used to create a smart microbial cell responding to pNP production from hydrolysis of an insecticide, paraoxon, in a coupled assay involving phosphotriesterase (PTE) enzyme expressed from a separate promoter. We show the fluorescence of the cells correlated with the catalytic efficiency of the PTE variant expressed in each cell. High selectivity between similar molecules (4HB versus pNP), high sensitivity for pNP detection (~2 μM) and agreement of apo- and holo-structures of PobR scaffold with predetermined computational models are other significant results presented in this work.

Jha, Ramesh K.↗
DOE OSTI2015

The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

The second crystal structure of a parasite protein preferentially enriched in the brain cyst of T. gondii has been solved at 2.75 Å resolution. Bradyzoite enolase 1 is reported to have differential functions as a glycolytic enzyme and a transcriptional regulator in bradyzoites. In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗