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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Comparisons Between NO PLIF Imaging and CFD Simulations of Mixing Flowfields for High-Speed Fuel Injectors

The current work compares experimentally and computationally obtained nitric oxide (NO) planar laser-induced fluorescence (PLIF) images of the mixing flowfields for three types of high-speed fuel injectors: a strut, a ramp, and a rectangular flushwall. These injection devices, which exhibited promising mixing performance at lower flight Mach numbers, are currently being studied as a part of the Enhanced Injection and Mixing Project (EIMP) at the NASA Langley Research Center. The EIMP aims to investigate scramjet fuel injection and mixing physics, and improve the understanding of underlying physical processes relevant to flight Mach numbers greater than eight. In the experiments conducted in the NASA Langley Arc-Heated Scramjet Test Facility (AHSTF), the injectors are placed downstream of a Mach 6 facility nozzle, which simulates the high Mach number air flow at the entrance of a scramjet combustor. Helium is used as an inert substitute for hydrogen fuel. Both schlieren and PLIF techniques are applied to obtain mixing flowfield flow visualizations. The experimental PLIF is obtained by using a UV laser sheet to interrogate a plane of the flow by exciting fluorescence from the NO molecules that are present in the AHSTF air. Consequently, the absence of signal in the resulting PLIF images is an indication of pure helium (fuel). The computational PLIF is obtained by applying a fluorescence model for NO to the results of the Reynolds-averaged simulations (RAS) of the mixing flowfield carried out using the VULCAN-CFD solver. This approach is required because the PLIF signal is a nonlinear function of not only NO concentration, but also pressure, temperature, and the flow velocity. This complexity allows additional flow features to be identified and compared with those obtained from the computational fluid dynamics (CFD) simulations, however, such comparisons are only semiquantitative. Three-dimensional image reconstruction, similar to that used in magnetic resonance imaging, is also used to obtain images in the streamwise and spanwise planes from select cross-stream PLIF plane data. Synthetic schlieren is also computed from the RAS data. Good agreement between the experimental and computational results provides increased confidence in the CFD simulations for investigations of injector performance.

PLIF↗
NASA NTRS2019

Inter-annual variation of tropical cyclones simulated by GEOS-5 AGCM with modified convection scheme

The Goddard Earth Observing System version 5 (GEOS-5) global climate model with a 50-km horizontal resolution is forced by observed sea surface temperature (SST) to examine the fidelity of the seasonal-mean and inter-annual variation of tropical cyclones (TCs) in the western North Pacific (WNP) and the North Atlantic (NATL). The standard Relaxed Arakawa Schubert (RAS) deep convection scheme is modified to improve the representation of TCs, where the scheme implements a stochastic limit of the cumulus entrainment rate. The modification drives mid- and upper-tropospheric cooling and low- to mid-tropospheric drying in the background state, which tends to increase atmospheric instability. This enables the model to increase convective variability on an intra-seasonal timescale and improve the simulation of intense storms. Five-member ensemble runs with the modified RAS scheme for 12 years (1998–2009) exhibit realistic spatial distributions in the climatological-mean TC development area and their pathways over WNP and NATL. The GCM is able to reproduce the inter-annual variation of accumulated cyclone energy (ACE) by prescribing yearly varying observed SST even though the individual TC intensity is still underpredicted. A sensitivity of TC activity to El Niño–Southern Oscillation (ENSO) phase is also reproduced realistically over WNP in terms of the spatial pattern changes in the main development region and TC pathways. However, the model exhibits a notable deficiency in NATL in reproducing the observed inter-annual variation of TC activity and the sensitivity to the ENSO.

accumulated cyclone energy↗
DOE OSTI2020

Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR

Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. SPRED1 and NF1 loss-of-function mutations occur across multiple cancer types and developmental diseases. Analysis of the neurofibromin-SPRED1 interface provides a rationale for mutations observed in Legius syndrome and suggests why SPRED1 can bind to neurofibromin but no other RasGAPs. We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Quantitative Proteomic Analysis of the Senescence-Associated Secretory Phenotype by Data-Independent Acquisition

Cellular senescence is a complex stress response that induces an essentially permanent cell cycle arrest and a complex secretory phenotype termed the senescence-associated secretory phenotype (SASP), which drives numerous aging pathologies. Characterization of the SASP can provide insights into aging and disease mechanisms, aging biomarker candidates, and targets for counteracting the deleterious effects of senescent cells. Here we describe a mass spectrometry (MS)-compatible protocol to (1) generate senescent cells using different stimuli, (2) collect conditioned medium containing proteins secreted by senescent cells (i.e., SASP), and (3) prepare the SASP for quantitative proteomic analysis using data-independent acquisition (DIA) MS. Basic Protocol 1: Generating ionizing radiation-induced senescent and control cells Alternate Protocol 1: Generating doxorubicin-induced senescent and control cells Alternate Protocol 2: Generating oncogenic RAS-induced senescent and control cells Alternate Protocol 3: Generating mitochondrial dysfunction-induced senescent and control cells Alternate Protocol 4: Generating atazanavir/ritonavir-induced senescent and control cells Support Protocol: A multiple-assay approach to confirm the phenotype of senescent cells Basic Protocol 2: Generating conditioned medium from senescent cells cultured in low serum and quiescent control cells Alternate Protocol 5: Generating conditioned medium from senescent cells cultured in complete medium and quiescent control cells Basic Protocol 3: Quantitative proteomic analysis of the SASP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Protein 4.1R negatively regulates P815 cells proliferation by inhibiting C-Kit-mediated signal transduction

The proliferation of mast cells (MCs) plays a crucial role in either physiological or pathological progression of human physical. C-Kit-mediated signaling pathway has been confirmed to play a key role in MCs proliferation, and the regulatory mechanisms of C-Kit-mediated MCs proliferation need to be further explored. Our previous study found that protein 4.1R could negatively regulate T cell receptor (TCR) mediated signal pathways in CD4{sup +} T cells. Little is known about the function of 4.1R in C-Kit-mediated proliferation of MCs. In this study, P815-4.1R{sup -/-} cells were constructed by using CRISPR/Cas9 technique. Lack of 4.1R significantly enhanced P815 cells proliferation by accelerating the progression of cell cycle. 4.1R could also significantly alleviate the clinical symptoms of systemic mastocytosis (SM) and improve the overall survival of SM mice. Further study showed that 4.1R could interact directly with C-Kit to inhibit the activation of C-Kit-mediated Ras-Raf-MAPKs and PI3K-AKT signal pathways. Taken together, our findings demonstrate that protein 4.1R, a novel negative regulator, negatively regulates MCs proliferation by inhibiting C-Kit-mediated signal transduction, which maybe provide a potential target to the prevention and treatment of abnormal MCs proliferation-related diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

RAN and YBX1 are required for cell proliferation and IL-4 expression and linked to poor prognosis in oral squamous cell carcinoma

Highlights: • RAN and YBX1 are co-expressed and required for cell proliferation in OSCC cells. • RAN and YBX1 are positively associated with the immune infiltrates of CD4{sup +} Th2 cells. • RAN and YBX1 can promote IL-4 expression. • RAN is a direct target of YBX1. • RAN and YBX1 can serve as potential co-biomarkers for poor prognosis in OSCC. Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the world, with a high mortality rate. RAN is a member of the Ras GTPase family and is overexpressed in a range of cancers, however, the relationship between RAN and OSCC is rarely reported. In this study, we found that RAN is overexpressed in OSCC tissues. RAN inhibition retarded OSCC cell proliferation and led to apoptosis and cell cycle arrest. Knockdown of RAN inhibited tumor growth in vivo. Strikingly, we found that RAN and oncogene Y-box binding protein-1 (YBX1) are positively associated with the immune infiltrates of CD4{sup +} Th2 cells in multiple types of cancer, and can promote IL-4 expression. IL-4 treatment can partially rescue RAN knockdown-induced cell apoptosis in OSCC cells. Moreover, overexpression of RAN could rescue cell growth inhibition caused by knockdown of YBX1. Furthermore, patients with low expression of both RAN and YBX1 had better overall survival than others. Collectively, these findings indicate that RAN is a target of YBX1. RAN and YBX1 are required for cell proliferation and IL-4 expression. RAN and YBX1 are co-expressed and can serve as potential co-biomarkers for poor prognosis in OSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Spin–Orbit Matrix Elements for a Combined Spin-Flip and IP/EA approach

We introduce a practical approach for computing the Breit–Pauli spin–orbit matrix elements of multiconfigurational systems with both spin and spatial degeneracies based on our recently developed RAS-nSF-IP/EA method (Houck, S. E.; et al. J. Chem. Theory Comput. 2019, 15, 2278). The spin–orbit matrix elements over all the multiplet components are computed using a single one-particle reduced density matrix as a result of the Wigner–Eckart theorem. A mean field spin–orbit approximation was used to account for the two-electron contributions. Basis set dependence as well as the effect of including additional excitations is presented. The effect of correlating the core and semicore orbitals is also examined. Surprisingly accurate results are obtained for spin–orbit coupling constants, despite the fact that the efficient wave function approximations we research neglect the bulk of dynamical correlation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Asynchronous Reciprocal Coupling of Martini 2.2 Coarse-Grained and CHARMM36 All-Atom Simulations in an Automated Multiscale Framework

The appeal of multiscale modeling approaches is predicated on the promise of combinatorial synergy. However, this promise can only be realized when distinct scales are combined with reciprocal consistency. Here, we consider multiscale molecular dynamics (MD) simulations that combine the accuracy and macromolecular flexibility accessible to fixed-charge all-atom (AA) representations with the sampling speed accessible to reductive, coarse-grained (CG) representations. AA-to-CG conversions are relatively straightforward because deterministic routines with unique outcomes are achievable. Conversely, CG-to-AA conversions have many solutions due to a surge in the number of degrees of freedom. While automated tools for biomolecular CG-to-AA transformation exist, we find that one popular option, called Backward, is prone to stochastic failure and the AA models that it does generate frequently have compromised protein structure and incorrect stereochemistry. Although these shortcomings can likely be circumvented by human intervention in isolated instances, automated multiscale coupling requires reliable and robust scale conversion. In this work, we detail an extension to Multiscale Machine-learned Modeling Infrastructure (MuMMI), including an improved CG-to-AA conversion tool called sinceCG. This tool is reliable (~98% weakly correlated repeat success rate), automatable (no unrecoverable hangs), and yields AA models that generally preserve protein secondary structure and maintain correct stereochemistry. We describe how the MuMMI framework identifies CG system configurations of interest, converts them to AA representations, and simulates them at the AA scale while on-the-fly analyses provide feedback to update CG parameters. Application to systems containing the peripheral membrane protein RAS and proximal components of RAF kinase on complex eight-component lipid bilayers with ~1.5 million atoms is discussed in the context of MuMMI.

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

Generating Protein Structures for Pathway Discovery Using Deep Learning

Resolving the intricate details of biological phenomena at the molecular level is fundamentally limited by both length- and time scales that can be probed experimentally. Molecular dynamics (MD) simulations at various scales are powerful tools frequently employed to offer valuable biological insights beyond experimental resolution. However, while it is relatively simple to observe long-lived, stable configurations of, for example, proteins, at the required spatial resolution, simulating the more interesting rare transitions between such states often takes orders of magnitude longer than what is feasible even on the largest supercomputers available today. One common aspect of this challenge is pathway discovery, where the start and end states of a scientific phenomenon are known or can be approximated, but the mechanistic details in between are unknown. Here, we propose a representation-learning-based solution that uses interpolation and extrapolation in an abstract representation space to synthesize potential transition states, which are automatically validated using MD simulations. The new simulations of the synthesized transition states are subsequently incorporated into the representation learning, leading to an iterative framework for targeted path sampling. Our approach is demonstrated by recovering the transition of a RAS-RAF protein domain (CRD) from membrane-free to interacting with the membrane using coarse-grain MD simulations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography

SOS1 and SOS2 are guanine nucleotide exchange factors that mediate RTK-stimulated RAS activation. Selective SOS1:KRAS PPI inhibitors are currently under clinical investigation, whereas there are no reports to date of SOS2:KRAS PPI inhibitors. SOS2 activity is implicated in MAPK rebound when divergent SOS1 mutant cell lines are treated with the SOS1 inhibitor BI-3406; therefore, SOS2:KRAS inhibitors are of therapeutic interest. In this report, we detail a fragment-based screening strategy to identify X-ray cocrystal structures of five diverse fragment hits bound to SOS2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

A Prefire Approach for Probabilistic Assessments of Postfire Debris‐Flow Inundation

Increases in wildfire activity and rainfall intensification are driving more postfire debris flows (PFDF) in many regions around the world. PFDFs are most common in the first postfire year and may even occur before a fire is fully controlled. This underscores the importance of assessing postfire hazards before a fire starts. Evaluation of PFDF hazards prior to fire can help strategize interventions lessening the negative effects of future fires. However, debris-flow runout and inundation analyses are not routine in PFDF hazard assessments, partially due to time constraints and substantial uncertainties in boundary conditions. Here, we propose a prefire PFDF inundation assessment framework using a debris-flow runout model based on the Herschel-Bulkley (HB) rheology (HEC-RAS v6.1). We constrain model inputs and parameters using Bayesian posterior analysis, rainfall-runoff simulations, and a debris-flow volume model. We use observations from recent PFDF incidents in northern Arizona, USA, to calibrate model components and then apply our prefire inundation assessment framework in a nearby unburned area. Specifically, we (a) identify yield stress as the most influential factor on inundation extent and arrival time in a HB model, (b) establish posterior distributions for model parameters suitable for forward modeling by leveraging uncertainties in field observations, and (c) implement a predictive forward analysis in an area that has not burned recently to evaluate PFDF inundation under several future fire scenarios. This study improves our ability to assess postfire debris-flow hazards before a fire begins and provides guidance for future applications of single-phase rheological models when assessing PFDF hazards.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

Campylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Machine-learning-based dynamic-importance sampling for adaptive multiscale simulations

Multiscale simulations are a well-accepted way to bridge the length and time scales required for scientific studies with the solution accuracy achievable through available computational resources. Traditional approaches either solve a coarse model with selective refinement or coerce a detailed model into faster sampling, both of which have limitations. Here, we present a paradigm of adaptive, multiscale simulations that couple different scales using a dynamic-importance sampling approach. Our method uses machine learning to dynamically and exhaustively sample the phase space explored by a macro model using microscale simulations and enables an automatic feedback from the micro to the macro scale, leading to a self-healing multiscale simulation. As a result, our approach delivers macro length and time scales, but with the effective precision of the micro scale. Our approach is arbitrarily scalable as well as transferable to many different types of simulations. Overall, our method made possible a multiscale scientific campaign of unprecedented scale to understand the interactions of RAS proteins with a plasma membrane in the context of cancer research running over several days on Sierra, which is currently the second-most-powerful supercomputer in the world.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Anisotropic interactions for continuum modeling of protein–membrane systems

In this work, a model for anisotropic interactions between proteins and cellular membranes is proposed for large-scale continuum simulations. The framework of the model is based on dynamic density functional theory, which provides a formalism to describe the lipid densities within the membrane as continuum fields while still maintaining the fidelity of the underlying molecular interactions. Within this framework, we extend recent results to include the anisotropic effects of protein–lipid interactions. As applications, we consider two membrane proteins of biological interest: a RAS–RAF complex tethered to the membrane and a membrane embedded G protein-coupled receptor. A strong qualitative and quantitative agreement is found between the numerical results and the corresponding molecular dynamics simulations. Combining the scope of continuum level simulations with the details from molecular level particle simulations enables research into protein–membrane behaviors at a more biologically relevant scale, which crucially can also be accessed via experiment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Imaging broadband soft X-ray transmission-grating spectrograph for a wavelength range λ > 111 Å

A family of aperiodic Mo/Be multilayer mirrors was designed for maximum uniform reflectivity in the ranges 111 – 138, 111 – 150, 111 – 200 and 111 – 222 Å at normal radiation incidence. The simulations took into account the existence of Mo-on-Be and Be-on-Mo transition layers. It was shown that the reflectivity may be as high as 10% in an octave wavelength range of 111 – 222 Å. We demonstrate the operation of an imaging transmission-grating spectrograph with a broadband Mo/Be multilayer mirror with a uniform reflectivity in the wavelength range 111 – 138 Å synthesised at the Institute for the Physics of Microstructures, RAS. The spectrograph was used to record the line spectra of multiply charged fluorine and magnesium ions from a laser-produced plasma. The role of the grating support structure in the formation of spectral source images is discussed. The spatial resolution of 50 μm is demonstrated. (laser applications and other topics in quantum electronics)

36 MATERIALS SCIENCE↗
DOE OSTI2020

Viricidal and bactericidal exciplex barrier-discharge lamps

A brief review is presented of investigations performed in 2002 – 2020 on ultraviolet inactivation of bacteria, vital cells, and viruses by using excilamps. The excilamp models that have been developed at the Institute of High-Current Electronics, SB RAS are briefly described. Scientific data acquired by now show that excilamps on KrCl{sup *}, KrBr{sup *}, and XeBr{sup *} molecules are an alternative to low-pressure mercury lamps with respect to optical parameters. These sources of optical radiation exhibit a bactericidal effect, and emission of KrCl and KrBr excilamps demonstrates viricidal action. The latter is actual due to expansion of coronavirus disease. (paper)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Generation of high-power few-cycle femtosecond IR pulses by double-chirp parametric amplification

We present an energy scalable configuration for the generation of high-power few-cycle femtosecond IR pulses based on the sequential parametric amplification of chirped radiation pulses at the idler (0.86 μm) and signal (1.39 μm) wavelengths from the multi-terawatt femtosecond laser system made at the Institute of Laser Physics, Siberian Branch of the Russian Academy of Sciences (ILP SB RAS). The configuration under consideration involves the sequential production of radiation pulses with centre wavelengths of 2.24, 3.56, and 7.25 μm. The conditions are determined for the generation of few-cycle pulses with a terawatt peak power in the 3.56 μm (15.8 fs, 1.5 cycles) and 7.25 μm (17.2 fs, shorter than one cycle) domains. The phase transfer between signal and idler waves in the double-chirp parametric amplification is investigated for the first time. (paper)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗