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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 739 records · Page 41
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer

Plekha7 (Pleckstrin homology [PH] domain containing, family A member 7) regulates the assembly of proteins of the cytoplasmic apical zonula adherens junction (AJ), thus ensuring cell-cell adhesion and tight-junction barrier integrity. Little is known of Plekha7 function in cancer. In colorectal cancer (CRC) Plekha7 expression is elevated compared to adjacent normal tissue levels, increasing with clinical stage. Plekha7 was present at plasma membrane AJ with wild-type KRas (wt-KRas) but was dispersed in cells expressing mutant KRas (mut-KRas). Fluorescence lifetime imaging microscopy (FLIM) indicated a direct Plekha7 interaction with wt-KRas but scantily with mut-KRas. Inhibiting Plekha7 specifically decreased mut-KRas cell signaling, proliferation, attachment, migration, and retarded mut-KRAS CRC tumor growth. Binding of diC8-phosphoinositides (PI) to the PH domain of Plekha7 was relatively low affinity. This may be because a D175 amino acid residue plays a “sentry” role preventing PI(3,4)P{sub 2} and PI(3,4,5)P{sub 3} binding. Molecular or pharmacological inhibition of the Plekha7 PH domain prevented the growth of mut-KRas but not wt-KRas cells. Taken together the studies suggest that Plekha7, in addition to maintaining AJ structure plays a role in mut-KRas signaling and phenotype through interaction of its PH domain with membrane mut-KRas, but not wt-KRas, to increase the efficiency of mut-KRas downstream signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Identification of Small-Molecule Inhibitors of Fibroblast Growth Factor 23 Signaling via In Silico Hot Spot Prediction and Molecular Docking to α-Klotho

Fibroblast growth factor 23 (FGF23) is a therapeutic target for treating hereditary and acquired hypophosphatemic disorders, such as X-linked hypophosphatemic (XLH) rickets and tumor-induced osteomalacia (TIO), respectively. FGF23-induced hypophosphatemia is mediated by signaling through a ternary complex formed by FGF23, the FGF receptor (FGFR), and α-Klotho. Currently, disorders of excess FGF23 are treated with an FGF23-blocking antibody, burosumab. Small-molecule drugs that disrupt protein/protein interactions necessary for the ternary complex formation offer an alternative to disrupting FGF23 signaling. In this study, the FGF23:α-Klotho interface was targeted to identify small-molecule protein/protein interaction inhibitors since it was computationally predicted to have a large fraction of hot spots and two druggable residues on α-Klotho. We further identified Tyr433 on the KL1 domain of α-Klotho as a promising hot spot and α-Klotho as an appropriate drug-binding target at this interface. Subsequently, we performed in silico docking of ~5.5 million compounds from the ZINC database to the interface region of α-Klotho from the ternary crystal structure. Following docking, 24 and 20 compounds were in the final list based on the lowest binding free energies to α-Klotho and the largest number of contacts with Tyr433, respectively. Herein, five compounds were assessed experimentally by their FGF23-mediated extracellular signal-regulated kinase (ERK) activities in vitro, and two of these reduced activities significantly. Both these compounds were predicted to have favorable binding affinities to α-Klotho but not have a large number of contacts with the hot spot Tyr433. ZINC12409120 was found experimentally to disrupt FGF23:α-Klotho interaction to reduce FGF23-mediated ERK activities by 70% and have a half maximal inhibitory concentration (IC50) of 5.0 ± 0.23 μM. Molecular dynamics (MD) simulations of the ZINC12409120:α-Klotho complex starting from in silico docking poses reveal that the ligand exhibits contacts with residues on the KL1 domain, the KL1–KL2 linker, and the KL2 domain of α-Klotho simultaneously, thereby possibly disrupting the regular function of α-Klotho and impeding FGF23:α-Klotho interaction. ZINC12409120 is a candidate for lead optimization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Ambient ion focusing from a field-free region to a detector: enhanced signal for explosives and drug detection with mass spectrometry

This study demonstrates ion focusing at ambient pressure and increased ion signal by creating a voltage gradient from a field-free region to a detector, thereby improving the detection of chemicals, such as explosives and drugs. At ambient pressure, ion loss and resulting signal reduction pose challenges that limit detection sensitivity in analytical instruments. Techniques to increase sensitivity, such as atmospheric flow tube-mass spectrometry (AFT-MS), extend ion-molecule reaction times but result in significant overall ion loss due to diffusion. Ion manipulation techniques, though challenging at ambient pressure, can mitigate these losses by concentrating ions toward the detector inlet. Using SIMION, ion trajectories were modeled with a voltage gradient applied between a flow tube and a detector, revealing ion focusing at ambient pressure. Experimental verification with an atmospheric flow tube employed both mass spectrometry and Faraday plate detectors to measure ion beam profiles across varying flow rates, tube diameters, and voltage gradients. Application of a voltage gradient effectively directed ions to the axial center of the flow tube, narrowed ion beam width, and increased signal intensity by 5 to 10 times compared to conditions without a voltage gradient. This ion focusing approach shows promise for improving sensitivity in ambient-pressure instruments. This technique has the potential to enhance detection levels in security and forensic applications, with particular benefits for field-portable devices used at checkpoints to identify explosives and drugs.

ambient pressure↗
DOE OSTI2020

Characteristics of Electron Precipitation During 40 Energetic Electron Injections Inferred via Subionospheric VLF Signal Propagation

Energetic electron injection events are associated with energetic electron precipitation (EEP) through possible resonant wave-particle interactions. Previous studies confirm the impacts of injection-driven precipitation on observed amplitude/phase of subionospheric VLF (very low frequency) signals transmitted from distant artificial transmitters. Currently, there are substantial uncertainties on precipitation characteristics and flux during injection events. In this work we study 40 injection events selected by Van Allen Probes particle data to investigate the changes in amplitude and phase of VLF signals at ground receivers across Canada during particle injection events. We model the ionospheric effect of the EEP flux to find its impact on VLF propagation and characterize the injection events. Typically, we find a clear phase advance of ~40° in the received VLF signal at Fort Smith (Canada, L = 8) transmitted from U.S. Navy communication transmitter NAA at Maine (USA). Comparing to other VLF transmitter-receiver paths in North America leads us to conclude that effects are only seen on paths with adequately large range >>200 km) through L > 7. Modeling the VLF phase change indicates that in the majority of events (>90%), less than 10% of the strong scattering limit inferred from particle flux measurements at the Van Allen Probes is required to obtain the observed VLF phase signature. The median precipitating flux during energetic particle injections is less than 4 × 10 6 el/cm 2 s sr (<10% of the strong scattering rate) for electrons above ~40 keV extracted from trapped particles energy spectrum. This implies that strong scattering is not typical for these 40 selected energetic electron injection events.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

Modeling the Transmission of Optical Lightning Signals Through Complex 3‐D Cloud Scenes

Abstract Space‐based lightning imagers have shown that complex cloud scenes consisting of multiple tall convective features, anvil clouds, and warm boundary cloud layers are illuminated by lightning in many different ways depending on where the lightning occurs and how energetic it is. Modifications to the optical lightning signals from radiative transfer in the cloud medium can lead to reductions in detection efficiency and location accuracy for these instruments and can also cause some of the optical signals that are detected to have unexpected spatial energy distributions. In this study, we perform Monte Carlo radiative transfer simulations of optical lightning emissions in clouds with complex 3‐D geometries to shed some light on the origins of certain irregular radiance patterns that have been recorded from orbit. We show that diffuse reflections off nearby cloud faces can explain lightning signals in nonelectrified clouds, tall clouds can result in poor optical transmission and suppressed radiances that could lead to missed events and that particularly favorable viewing conditions can cause otherwise normal lightning to produce a superbolt that is orders of magnitude brighter than the same flash seen from a different angle.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Isolating Detrital and Diagenetic Signals in Magnetic Susceptibility Records From Methane‐Bearing Marine Sediments

Abstract Volume‐dependent magnetic susceptibility (κ) is commonly used for paleoenvironmental reconstructions in both terrestrial and marine sedimentary environments where it reflects a mixed signal between primary deposition and secondary diagenesis. In the marine environment, κ is strongly influenced by the abundance of ferrimagnetic minerals regulated by sediment transport processes. Post‐depositional alteration by H 2 S, however, can dissolve titanomagnetite, releasing reactive Fe that promotes pyritization and subsequently decreases κ. Here, we provide a new approach for isolating the detrital signal in κ and identifying intervals of diagenetic alteration of κ driven by organoclastic sulfate reduction (OSR) and the anaerobic oxidation of methane (AOM) in methane‐bearing marine sediments offshore India. Using the correlation of a heavy mineral proxy from X‐ray fluorescence data (Zr/Rb) and κ in unaltered sediments, we predict the primary detrital κ signal and identify intervals of decreased κ, which correspond to increased total sulfur content. Our approach is a rapid, high‐resolution method that can identify overprinted κ resulting from pyritization of titanomagnetite due to H 2 S production in marine sediments. In addition, total organic carbon, total sulfur, and authigenic carbonate δ 13 C measurements indicate that both OSR and AOM can drive the observed κ loss, but AOM drives the greatest decreases in κ. Overall, our approach can enhance paleoenvironmental reconstructions and provide insight into paleo‐positions of the sulfate‐methane transition zone, past enhancements of OSR or paleo‐methane seepage, and the role of detrital iron oxide minerals on the marine sediment sulfur sink, with consequences influencing the development of chemosynthetic biological communities at methane seeps.

58 GEOSCIENCES↗
DOE OSTI2020

Non-equilibrium signal integration in hydrogels

Abstract Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the non-monotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF

Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF trimer forms a complex with a dimer of TNFR1 molecules. This observation, along with data from a solution-based network assembly assay, leads us to suggest a model for TNF signalling based on TNF-TNFR1 clusters, which are disrupted by small molecule inhibitors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Towards single-chip radiofrequency signal processing via acoustoelectric electron–phonon interactions

Abstract The addition of active, nonlinear, and nonreciprocal functionalities to passive piezoelectric acoustic wave technologies could enable all-acoustic and therefore ultra-compact radiofrequency signal processors. Toward this goal, we present a heterogeneously integrated acoustoelectric material platform consisting of a 50 nm indium gallium arsenide epitaxial semiconductor film in direct contact with a 41° YX lithium niobate piezoelectric substrate. We then demonstrate three of the main components of an all-acoustic radiofrequency signal processor: passive delay line filters, amplifiers, and circulators. Heterogeneous integration allows for simultaneous, independent optimization of the piezoelectric-acoustic and electronic properties, leading to the highest performing surface acoustic wave amplifiers ever developed in terms of gain per unit length and DC power dissipation, as well as the first-ever demonstrated acoustoelectric circulator with an isolation of 46 dB with a pulsed DC bias. Finally, we describe how the remaining components of an all-acoustic radiofrequency signal processor are an extension of this work.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Signal propagation in reversible digital mechanics

Digital mechanics explores information processing through binary, mechanical circuits. This work demonstrates a flexural, mechanical integrated circuit (m-IC) that achieves reversible, non-reciprocal signal propagation through integrated AND logic and memory. Our approach exploits sequential bistable transitions with symmetric energy wells, tunable stiffness, impedance matching, and AND gate non-linearity, to enable signal propagation, repeatability, and reversibility. We present a generalized model of logic kinematics and energetics, validated experimentally, to study energy flows, quantify energetic limits, and identify operating regimes for reversible logic. Macro-scale experiments confirm propagation dynamics, and new fabrication methods extend the architecture to micro-scale devices. By achieving controlled, reversible signal transmission across interconnected logic and memory, this work establishes a scalable platform for robust mechanical computing and adaptive sensing.

Johnson, Hilary A. [Lawrence Livermore National La↗
DOE OSTI2020

Real-Time Movement-Based Traffic Volume Prediction at Signalized Intersections

The traffic volume of each movement at signalized intersections can provide valuable information on real-time traffic conditions that enable traffic control systems to dynamically respond to the fluctuated traffic demands. Real-time movement-based traffic volume prediction is challenging due to various nonlinear spatial relationships at different locations/approaches and the complicated underlying temporal dependencies. In this study, a novel deep intersection spatial-temporal network (DISTN) is developed for real-time movement-based traffic volume prediction at signalized intersections, which considers both spatial and temporal features by the convolutional neural network (CNN) and long short-term memory (LSTM), respectively. In addition, the within-day, daily, and weekly periodic trends of traffic volume are also considered in the proposed model. This is the first time that a deep-learning method has been applied for movement-based traffic volume prediction at signalized intersections. In the numerical experiment, the proposed model is evaluated using real-world data and simulation data to demonstrate its effectiveness. The impacts of various structures of traffic networks on the proposed model are also discussed. Results show that the proposed model outperforms some of the state-of-the-art volume prediction methods currently in the literature.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Watching a signaling protein function: What has been learned over four decades of time-resolved studies of photoactive yellow protein

Photoactive yellow protein (PYP) is a signaling protein whose internal p-coumaric acid chromophore undergoes reversible, light-induced trans-to-cis isomerization, which triggers a sequence of structural changes that ultimately lead to a signaling state. Since its discovery nearly 40 years ago, PYP has attracted much interest and has become one of the most extensively studied proteins found in nature. The method of time-resolved crystallography, pioneered by Keith Moffat, has successfully characterized intermediates in the PYP photocycle at near atomic resolution over 12 decades of time down to the sub-picosecond time scale, allowing one to stitch together a movie and literally watch a protein as it functions. But how close to reality is this movie? To address this question, results from numerous complementary time-resolved techniques including x-ray crystallography, x-ray scattering, and spectroscopy are discussed. Emerging from spectroscopic studies is a general consensus that three time constants are required to model the excited state relaxation, with a highly strained ground-state cis intermediate formed in less than 2.4 ps. Persistent strain drives the sequence of structural transitions that ultimately produce the signaling state. Crystal packing forces produce a restoring force that slows somewhat the rates of interconversion between the intermediates. Moreover, the solvent composition surrounding PYP can influence the number and structures of intermediates as well as the rates at which they interconvert. When chloride is present, the PYP photocycle in a crystal closely tracks that in solution, which suggests the epic movie of the PYP photocycle is indeed based in reality.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Studying fast-ion populations using oscillations in solid-state neutral-particle analyzer signal and neutral-beam injection power

A method for determining the fast-ion population density in magnetically confined plasmas as a function of pitch-radius, (λ, R), using a solid-state neutral-particle analyzer (ssNPA) signal and neutral-beam injection (NBI) power-output data has been developed. Oscillations in the NBI power output are replicated only in the active part of the ssNPA signal, allowing this to be separated from the passive and background signals, which usually complicate data from this diagnostic. Results obtained using this method are compared with those from standard techniques using data from the Mega-Amp Spherical Tokamak Upgrade spherical tokamak.

Instruments & Instrumentation↗
DOE OSTI2024

Direct mechanistic connection between acoustic signals and melt pool morphology during laser powder bed fusion

Various nondestructive diagnostic techniques have been proposed for in situ process monitoring of laser powder bed fusion (LPBF), including melt pool pyrometry, whole-layer optical imaging, acoustic emission, atomic emission spectroscopy, high speed melt pool imaging, and thermionic emission. Correlations between these in situ monitoring signals and defect formation have been demonstrated with acoustic signals having been shown to predict pore formation with especially high confidence in recent machine learning studies. Here, in this work, time-resolved acoustic data are collected in both the conduction and keyhole welding regimes of LPBF-processed Ti-6Al-4V alloy. A non-dimensionalized Strouhal number analysis, used in whistle aeroacoustics, is applied to demonstrate that the acoustic signals recorded in the keyhole regimes can be directly associated with the vapor depression morphology. This mechanistic understanding developed from whistle aeroacoustics shows that acoustic monitoring during the LPBF process can provide a direct probe into the vapor depression dynamics and defect occurrence, especially in the keyhole regimes relevant to printing and defect formation.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Differential roles of kinetic on- and off-rates in T-cell receptor signal integration revealed with a modified Fab’-DNA ligand

Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells. While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell signal integration mechanisms that rely on monovalent, membrane-associated, and relatively weakly binding ligand in the context of cellular adhesion. Commonly used antibodies and their derivatives bind much more strongly than native peptide major histocompatibility complex (pMHC) ligands bind their cognate TCRs. Because ligand dwell time is a critical parameter that tightly correlates with physiological function of the TCR signaling system, there is a general need, both in research and therapeutics, for universal TCR ligands with controlled kinetic binding parameters. To this end, we have introduced point mutations into recombinantly expressed α-TCRβ H57 Fab to modulate the dwell time of monovalent Fab binding to TCR. When tethered to a supported lipid bilayer via DNA complementation, these monovalent Fab’-DNA ligands activate T cells with potencies well-correlated with their TCR binding dwell time. Single-molecule tracking studies in live T cells reveal that individual binding events between Fab'-DNA ligands and TCRs elicit local signaling responses closely resembling native pMHC. The unique combination of high on- and off-rates of the H57 R97L mutant enables direct observations of cooperative interplay between ligand binding and TCR-proximal condensation of the linker for activation of T cells, which is not readily visualized with pMHC. This work provides insights into how T cells integrate kinetic information from TCR ligands and introduces a method to develop affinity panels for polyclonal T cells, such as cells from a human patient.

Science & Technology - Other Topics↗
DOE OSTI2022

A Forward Analytic Model of Neutron Time-of-Flight Signals for Inferring Ion Temperatures from MagLIF Experiments

A forward analytic model is required to rapidly simulate the neutron time-of-flight (nToF) signals that result from magnetized liner inertial fusion (MagLIF) experiments at Sandia’s Z Pulsed Power Facility. Various experimental parameters, such as the burn-weighted fuel-ion temperature and liner areal density, determine the shape of the nToF signal and are important for characterizing any given MagLIF experiment. Extracting these parameters from measured nToF signals requires an appropriate analytic model that includes the primary deuterium-deuterium neutron peak, once-scattered neutrons in the beryllium liner of the MagLIF target, and direct beamline attenuation. Here, mathematical expressions for this model were derived from the general-geometry time- and energy-dependent neutron transport equation with anisotropic scattering. Assumptions consistent with the time-of-flight technique were used to simplify this linear Boltzmann transport equation into a more tractable form. Models of the uncollided and once-collided neutron scalar fluxes were developed for one of the five nToF detector locations at the Z-Machine. Numerical results from these models were produced for a representative MagLIF problem and found to be in good agreement with similar neutron transport simulations. Twenty experimental MagLIF data sets were analyzed using the forward models, which were determined to only be significantly sensitive to the ion temperature. The results of this work were also found to agree with values obtained separately using a zero scatter analytic model and a high-fidelity Monte Carlo simulation. Finally, inherent difficulties in this and similar techniques are identified, and a new approach forward is suggested.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2024

Ultrafast x-ray scattering and electronic coherence at avoided crossings: complete isotropic signals

Abstract Nonadiabatic transitions at conical intersections and avoided crossings play a pivotal role in shaping the outcomes of photochemical reactions. Using the photodissociation of LiF as a model, this theoretical study explores the application of gas phase nonresonant ultrafast x-ray scattering to map nonadiabatic transitions at an avoided crossing, utilizing the part of the scattering signal that probes electronic coherence directly. The presented scattering signals are rotationally averaged and calculated from two- rather than one-electron (transition) densities, which inherently accounts for all possible electronic transitions driven by the x-ray photon. This approach provides quantitative predictions of the experimental signals, thereby facilitating future experimental endeavors to observe nonadiabatic effects and coherent electron dynamics with ultrafast x-ray scattering.

Optics↗
DOE OSTI2020

Analysis of 83m Kr prompt scintillation signals in the PIXeY detector

Prompt scintillation signals from 83m Kr calibration sources are a useful metric to calibrate the spatial variation of light collection efficiency and electric field magnitude of a two phase liquid-gas xenon time projection chamber. Because 83m Kr decays in two steps, there are two prompt scintillation pulses for each calibration event, denoted S1a and S1b. We study the ratio of S1b to S1a signal sizes in the Particle Identification in Xenon at Yale (PIXeY) experiment and its dependence on the time separation between the two signals (Δ t), notably its increase at low Δ t. Finally, in PIXeY data, the Δ t dependence of S1b/S1a is observed to exhibit two exponential components: one with a time constant of 0.05 ± 0.02 μ s, which can be attributed to processing effects and pulse overlap and one with a time constant of 10.2 ± 2.2 μs that increases in amplitude with electric drift field, the origin of which is not yet understood.

47 OTHER INSTRUMENTATION↗