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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

High-accuracy Geant4 simulation and semi-analytical modeling of nuclear resonance fluorescence

Nuclear resonance fluorescence (NRF) is a photonuclear interaction that enables highly isotope-specific measurements in both pure and applied physics scenarios. High-accuracy design and analysis of NRF measurements in complex geometries is aided by Monte Carlo simulations of photon physics and transport, motivating Jordan and Warren (2007) to develop the G4NRF codebase for NRF simulation in Geant4. In this work, we enhance the physics accuracy of the G4NRF code and perform improved benchmarking simulations. The NRF cross section calculation in G4NRF, previously a Gaussian approximation, has been replaced with a full numerical integration for improved accuracy in thick-target scenarios. A high-accuracy semi-analytical model of expected NRF count rates in a typical NRF measurement is then constructed and compared against G4NRF simulations for both simple homogeneous and more complex heterogeneous geometries. Furthermore, agreement between rates predicted by the semi-analytical model and G4NRF simulation is found at a level of ~1% in simple test cases and ~3% in more realistic scenarios, improving upon the ~20% level of the initial benchmarking study and establishing a highly-accurate NRF framework for Geant4.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2025

Applying Gaussian Process Machine Learning and Modern Probabilistic Programming to Satellite Data to Infer CO 2 Emissions

Satellite data provides essential insights into the spatiotemporal distribution of CO 2 concentrations. However, many atmospheric inverse models fail to adequately incorporate the spatial and temporal correlations inherent in satellite observations and often lack rigorous methods for estimating parameters like spatial length scales. We introduce an inference model that processes the spatiotemporal covariance in satellite data and estimates hyperparameters such as covariance length scales. Our approach uses the Gaussian process (GP) machine learning (ML) and modern probabilistic programming languages (PPLs) to perform atmospheric inversions of emissions from satellite data. We develop a GP ML inversion system based on modern PPLs and the GEOS-Chem chemical transport model, simulating atmospheric CO 2 concentrations corresponding to the Orbiting Carbon Observatory-2/3 (OCO-2/3) data for July 2020. In our supervised learning framework, we treat the GEOS-Chem simulated data set as the target, with predictors derived by scaling the target with sector-specific factors hidden from the GP machine. Our results show that the GP model, combined with GPU-enabled PPLs, effectively retrieves true emission scaling factors and infers noise levels concealed within the data. This suggests that our method could be applied over larger areas with more complex covariance structures, enabling comprehensive analysis of the spatiotemporal patterns observed in OCO-2/3 and similar satellite data sets.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR·ligand complexes. The ensuing structure–function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease-related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. We conclude these findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Interdisciplinary round-robin test on molecular spectroscopy of the U(VI) acetate system

In the advent of the 2nd International Workshop on Advanced Techniques in Actinide Spec-troscopy (ATAS 2014), an inter-laboratory round-robin test (RRT) was initiated. The main goal of this RRT was the comprehensive molecular analysis of a simple aqueous complexing system – U(VI) acetate – which was selected to be independently investigated by various 100 spectroscopic (vibrational, luminescence, X-ray absorption, and nuclear magnetic resonance spectroscopy) and quantum chemical methods applied by leading laboratories in actinide or geochemical research. Ultimately, more than 40 scientists hosted at 20 institutions in 7 coun-tries participated. The outcome of this RRT were considered on two levels: First, conformities as well as 105 discrepancies in the results of each spectroscopic technique and their sources were evaluated. The raw data from the experimental approaches were found to be generally consistent. In particular, for complex setups such as accelerator-based X-ray absorption spectroscopy, the agreement between the raw data was surprisingly high. By contrast, the data obtained using luminescence spectroscopy turned out to be strongly related to the chosen acquisition param-110 eters. Second, the potentials and limitations of coupling various spectroscopic and, in partic-ular, theoretical approaches for the comprehensive study of actinide molecule complexes were assessed. The additional benefits of the combined approach with regard to the explora-tion of the aqueous speciation of the U(VI) acetate system were elaborated.

Muller, Katharina↗
DOE OSTI2023

A Simple and Flexible Infusion Platform for Automated Native Mass Spectrometry Analysis

High throughput native mass spectrometry analysis of proteins and protein complexes has been enabled by recent development of infusion and liquid chromatography (LC) systems, which often include complete LC pumps without fully utilizing their gradient flows. We demonstrated a lower-cost infusion cart for native mass spectrometry applications using a single isocratic solvent pump that can operate at both nano- and high-flow configurations (0.05-150 $μ$L/min) for both infusion and online buffer exchange experiments. In conclusion, the platform is controlled via open-source software and can potentially be expanded for customized experimental designs, offering a lower cost alternative to laboratories with limited budgets and/or needs in student training.

47 OTHER INSTRUMENTATION↗
DOE OSTI2017

Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel

Whereas screening of the small-molecule metabolites produced by most cultivatable microorganisms often results in the rediscovery of known compounds, genome-mining programs allow researchers to harness much greater chemical diversity, and result in the discovery of new molecular scaffolds. Here we report the genome-guided identification of a new antibiotic, klebsazolicin (KLB), from Klebsiella pneumoniae that inhibits the growth of sensitive cells by targeting ribosomes. A ribosomally synthesized post-translationally modified peptide (RiPP), KLB is characterized by the presence of a unique N-terminal amidine ring that is essential for its activity. Biochemical in vitro studies indicate that KLB inhibits ribosomes by interfering with translation elongation. Structural analysis of the ribosome–KLB complex showed that the compound binds in the peptide exit tunnel overlapping with the binding sites of macrolides or streptogramin-B. KLB adopts a compact conformation and largely obstructs the tunnel. Engineered KLB fragments were observed to retain in vitro activity, and thus have the potential to serve as a starting point for the development of new bioactive compounds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Revealing nano-scale lattice distortions in implanted material with 3D Bragg ptychography

Small ion-irradiation-induced defects can dramatically alter material properties and speed up degradation. Unfortunately, most of the defects irradiation creates are below the visibility limit of state-of-the-art microscopy. As such, our understanding of their impact is largely based on simulations with major unknowns. Here we present an x-ray crystalline microscopy approach, able to image with high sensitivity, nano-scale 3D resolution and extended field of view, the lattice strains and tilts in crystalline materials. Using this enhanced Bragg ptychography tool, we study the damage helium-ion-irradiation produces in tungsten, revealing a series of crystalline details in the 3D sample. Our results lead to the conclusions that few-atom-large ‘invisible’ defects are likely isotropic in orientation and homogeneously distributed. A partially defect-denuded region is observed close to a grain boundary. These findings open up exciting perspectives for the modelling of irradiation damage and the detailed analysis of crystalline properties in complex materials.

42 ENGINEERING↗
DOE OSTI2019

Multiplexed in-gel microfluidic immunoassays: characterizing protein target loss during reprobing of benzophenone-modified hydrogels

From whole tissues to single-cell lysate, heterogeneous immunoassays are widely utilized for analysis of protein targets in complex biospecimens. Recently, benzophenone-functionalized hydrogel scaffolds have been used to immobilize target protein for immunoassay detection with fluorescent antibody probes. In benzophenone-functionalized hydrogels, multiplex target detection occurs via serial rounds of chemical stripping (incubation with sodium-dodecyl-sulfate (SDS) and β-mercaptoethanol at 50-60 °C for ≥1 h), followed by reprobing (interrogation with additional antibody probes). Although benzophenone facilitates covalent immobilization of proteins to the hydrogel, we observe 50% immunoassay signal loss of immobilized protein targets during stripping rounds. Here, we identify and characterize signal loss mechanisms during stripping and reprobing. We posit that loss of immobilized target is responsible for ≥50% of immunoassay signal loss, and that target loss is attributable to disruption of protein immobilization by denaturing detergents (SDS) and incubation at elevated temperatures. Furthermore, our study suggests that protein losses under non-denaturing conditions are more sensitive to protein structure (i.e., hydrodynamic radius), than to molecular mass (size). We formulate design guidance for multiplexed in-gel immunoassays, including that low-abundance proteins be immunoprobed first, even when targets are covalently immobilized to the gel. We also recommend careful scrutiny of the order of proteins targets detected via multiple immunoprobing cycles, based on the protein immobilization buffer composition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Finite-difference time-domain methods

The finite-difference time-domain (FDTD) method is a widespread numerical tool for full-wave analysis of electromagnetic fields in complex media and for detailed geometries. Applications of the FDTD method cover a range of time and spatial scales, extending from subatomic to galactic lengths and from classical to quantum physics. Technology areas that benefit from the FDTD method include biomedicine — bioimaging, biophotonics, bioelectronics and biosensors; geophysics — remote sensing, communications, space weather hazards and geolocation; metamaterials — sub-wavelength focusing lenses, electromagnetic cloaks and continuously scanning leaky-wave antennas; optics — diffractive optical elements, photonic bandgap structures, photonic crystal waveguides and ring-resonator devices; plasmonics — plasmonic waveguides and antennas; and quantum applications — quantum devices and quantum radar. This Primer summarizes the main features of the FDTD method, along with key extensions that enable accurate solutions to be obtained for different research questions. Additionally, hardware considerations are discussed, plus examples of how to extract magnitude and phase data, Brillouin diagrams and scattering parameters from the output of an FDTD model. Furthermore, the Primer ends with a discussion of ongoing challenges and opportunities to further enhance the FDTD method for current and future applications.

42 ENGINEERING↗
DOE OSTI2015

Development of peptoid-based ligands for the removal of cadmium from biological media

Cadmium poisoning poses a serious health concern due to cadmium's increasing industrial use, yet there is currently no recommended treatment. The selective coordination of cadmium in a biological environment—i.e. in the presence of serum ions, small molecules, and proteins—is a difficult task. To address this challenge, a combinatorial library of peptoid-based ligands has been evaluated to identify structures that selectively bind to cadmium in human serum with minimal chelation of essential metal ions. Eighteen unique ligands were identified in this screening procedure, and the binding affinity of each was measured using metal titrations monitored by UV-vis spectroscopy. To evaluate the significance of each chelating moiety, sequence rearrangements and substitutions were examined. Analysis of a metal–ligand complex by NMR spectroscopy highlighted the importance of particular residues. Depletion experiments were performed in serum mimetics and human serum with exogenously added cadmium. These depletion experiments were used to compare and demonstrate the ability of these peptoids to remove cadmium from blood-like mixtures. In one of these depletion experiments, the peptoid sequence was able to deplete the cadmium to a level comparable to the reported acute toxicity limit. Evaluation of the metal selectivity in buffered solution and in human serum was performed to verify minimal off-target binding. These studies highlight a screening platform for the identification of metal–ligands that are capable of binding in a complex environment. They additionally demonstrate the potential utility of biologically-compatible ligands for the treatment of heavy metal poisoning.

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

Direct photoisomerization of CH 2 I 2 vs. CHBr 3 in the gas phase: a joint 50 fs experimental and multireference resonance-theoretical study

Femtosecond transient absorption measurements powered by 40 fs laser pulses reveal that ultrafast isomerization takes place upon S1 excitation of both CH2I2 and CHBr3 in the gas phase. The photochemical conversion process is direct and intramolecular, i.e., it proceeds without caging media that have long been implicated in the photo-induced isomerization of polyhalogenated alkanes in condensed phases. Using complete active space second order perturbation theory (CASPT2) calculations, we investigate the structure of the photochemical reaction paths connecting the photoexcited species to their corresponding isomeric forms. Unconstrained minimum energy paths computed starting from the S1 Franck-Condon points lead to S1/S0 conical intersections, which directly connect the parent CHBr3 and CH2I2 molecules to their isomeric forms. Changes in the chemical bonding picture along the S1/S0 isomerization reaction path are described using multireference average coupled pair functional (MRACPF) calculations in conjunction with natural resonance theory (NRT) analysis. These calculations reveal a complex interplay between covalent, radical, ylidic, and ion-pair dominant resonance structures throughout the nonadiabatic photochemical isomerization processes described in this work.

Borin, Veniamin A.↗
DOE OSTI2026

Mutation of active site glutamate in serine hydroxymethyltransferase allows trapping a reactive intermediate: a combined neutron and X-ray crystallography study

Serine hydroxymethyltransferase (SHMT) is a pyridoxal-5′-phosphate (PLP) dependent enzyme that catalyzes a chemical transformation essential for the one-carbon (1C) metabolism. SHMT reversibly converts L-Ser into Gly and transfers a 1C unit to tetrahydrofolate (THF) to give 5,10-methylene-THF (5,10-MTHF). 5,10-MTHF, a 1C-unit donor, plays a crucial role in the downstream biomolecular syntheses required for the cell homeostasis and proliferation. SHMT is a prominent target for the drug discovery to battle bacterial and parasitic infections, and to treat various types of cancer. SHMT-catalyzed chemistry is governed by the general acid-base catalysis. Knowledge of the catalytic mechanism can aid drug design but can only be achieved when the atomic details of each reaction step are mapped, including accurate determination of hydrogen atom positions. Here we utilized the inactive E53Q mutant of Thermus thermophilus ( Tth ) SHMT to directly determine protonation states with room-temperature neutron crystallography and to capture a reactive intermediate containing the PLP-L-Ser external aldimine and THF in the enzyme active site. We observed protonation of the Schiff base nitrogen (N SB ) in the PLP internal aldimine but no change in the protonation states of other ionizable PLP groups and active site residues compared to wild-type Tth SHMT. X-ray structural analysis of the ternary intermediate complex E53Q-Ser-THF that eluded previous structural characterization shows the strategic positioning of the E53Q side chain in close proximity to the external aldimine and THF and reinforces the proposed role for E53 as the driver of proton transfer events along the reaction pathway.

Drago, Victoria N. [Oak Ridge National Laboratory ↗
DOE OSTI2016

Fourier-transform spectroscopy and deperturbation analysis of the spin-orbit coupled A{sup 1}Σ{sup +} and b{sup 3}Π states of KRb

Fourier-transform A{sup 1}Σ{sup +} − b{sup 3}Π → X{sup 1}Σ{sup +} laser-induced fluorescence spectra were recorded for the natural mixture of {sup 39,41}K{sup 85,87}Rb isotopologues produced in a heatpipe oven. Overall 4200 rovibronic term values of the spin-orbit coupled A{sup 1}Σ{sup +} and b{sup 3}Π states were determined with an uncertainty of about 0.01 cm{sup −1} in the energy range [10 850, 14 200] cm{sup −1} covering rotational quantum numbers J′ ∈ [3, 280]. Direct deperturbation analysis of the A ∼ b complex performed within the framework of the A{sup 1}Σ{sup +} ∼ b{sup 3}Π{sub Ω=0,1,2} coupled-channel approach reproduced experimental data with a standard deviation of 0.004 cm{sup −1}. Initial parameters of the internuclear potentials and spin-orbit coupling functions along with the relevant transition dipole moments were obtained by performing the quasi-relativistic electronic structure calculations. The mass-invariant molecular parameters obtained from the fit were used to predict energy and radiative properties of the A ∼ b complex for low J levels of {sup 39}K{sup 85}Rb as well as for {sup 41}K{sup 87}Rb isotopologues, allowing us to identify the most reasonable candidates for the stimulated Raman transitions between the initial uppermost vibrational levels of the a{sup 3}Σ{sup +} and X{sup 1}Σ{sup +} states, the intermediate levels of the A ∼ b complex, and the lowest absolute ground X{sup 1}Σ{sup +}(v = 0, J = 0) state.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

XeCl*-laser discharge instabilities at high gas pressures

We discuss new features of the XeCl*-laser kinetics by using a detailed analysis of the results of complex computer models. In particular, we consider the development of a high scale instability in a XeCl*-laser discharge. The emphasis is made on fundamental problems, mainly on the limitation of the macroscopic approach to the study of such strongly nonequilibrium systems. The results obtained indicate especially the discharge proprieties at the plasma centre.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2012

Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes nosocomial infections for which there are limited treatment options. Penicillin-binding protein PBP3, a key therapeutic target, is an essential enzyme responsible for the final steps of peptidoglycan synthesis and is covalently inactivated by {beta}-lactam antibiotics. Here we disclose the first high resolution cocrystal structures of the P. aeruginosa PBP3 with both novel and marketed {beta}-lactams. These structures reveal a conformational rearrangement of Tyr532 and Phe533 and a ligand-induced conformational change of Tyr409 and Arg489. The well-known affinity of the monobactam aztreonam for P. aeruginosa PBP3 is due to a distinct hydrophobic aromatic wall composed of Tyr503, Tyr532, and Phe533 interacting with the gem-dimethyl group. The structure of MC-1, a new siderophore-conjugated monocarbam complexed with PBP3 provides molecular insights for lead optimization. Importantly, we have identified a novel conformation that is distinct to the high-molecular-weight class B PBP subfamily, which is identifiable by common features such as a hydrophobic aromatic wall formed by Tyr503, Tyr532, and Phe533 and the structural flexibility of Tyr409 flanked by two glycine residues. This is also the first example of a siderophore-conjugated triazolone-linked monocarbam complexed with any PBP. Energetic analysis of tightly and loosely held computed hydration sites indicates protein desolvation effects contribute significantly to PBP3 binding, and analysis of hydration site energies allows rank ordering of the second-order acylation rate constants. Taken together, these structural, biochemical, and computational studies provide a molecular basis for recognition of P. aeruginosa PBP3 and open avenues for future design of inhibitors of this class of PBPs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

The small protein SbtC is a functional component of the CO 2 concentrating mechanism in Synechocystis sp. PCC 6803

Oxygenic phototrophs fix CO 2 via the enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which shows relatively low CO 2 affinity and specificity. To circumvent low and fluctuating CO 2 concentrations in aquatic systems, cyanobacteria and algae have evolved sophisticated inorganic carbon (Ci) concentrating mechanisms (CCMs). Bicarbonate transporters such as SbtA play a crucial role in the cyanobacterial CCM and hence display multiple layers of tight regulation. Control of sbtA gene expression and corresponding transporter activity involves the PII-like protein SbtB, whose gene is frequently co-transcribed with sbtA. A previously non-annotated gene located upstream of the sbtAB operon in the model Synechocystis sp. PCC 6803 encodes the small protein SbtC, composed of 80 amino acids. Presence of SbtC was confirmed by immunoblotting of the sbtC-coding sequence fused to a Flag-tag. Similar to sbtAB , transcription of the sbtC locus is induced by low CO 2 availability; however, it is controlled independently. Mutation of the sbtC locus in a wild-type background produced only a mild phenotype, even under low CO 2 , but impaired diurnal growth resembled that of the mutant ΔsbtB . Biochemical analysis indicated a trimeric SbtABC complex in the membrane. Bicarbonate leakage from cells was strongly elevated when either sbtB or sbtC was deleted from recombinant Synechocystis strains harboring only SbtA as single Ci uptake system. Here, our results provide evidence that SbtC contributes to the formation of the SbtAB complex, thereby regulating bicarbonate exchange at the cytoplasmic membrane. Well-conserved SbtC-like proteins encoded in the neighborhood of sbtAB exist in many cyanobacterial genomes, pointing toward an important role in the cyanobacterial CCM.

Walke, Peter [Univ. of Rostock (Germany)] (ORCID:0↗
DOE OSTI2015

A national facility for biological cryo-electron microscopy

This review provides a brief update on the use of cryo-electron microscopy for integrated structural biology, along with an overview of the plans for the UK national facility for electron microscopy being built at the Diamond synchrotron. Three-dimensional electron microscopy is an enormously powerful tool for structural biologists. It is now able to provide an understanding of the molecular machinery of cells, disease processes and the actions of pathogenic organisms from atomic detail through to the cellular context. However, cutting-edge research in this field requires very substantial resources for equipment, infrastructure and expertise. Here, a brief overview is provided of the plans for a UK national three-dimensional electron-microscopy facility for integrated structural biology to enable internationally leading research on the machinery of life. State-of-the-art equipment operated with expert support will be provided, optimized for both atomic-level single-particle analysis of purified macromolecules and complexes and for tomography of cell sections. The access to and organization of the facility will be modelled on the highly successful macromolecular crystallography (MX) synchrotron beamlines, and will be embedded at the Diamond Light Source, facilitating the development of user-friendly workflows providing near-real-time experimental feedback.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗