Search NASA⌕ Search

SEARCH · Search NASA

Results for “Providence”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

A nanobody suite for yeast scaffold nucleoporins provides details of the nuclear pore complex structure

Nuclear pore complexes (NPCs) are the main conduits for molecular exchange across the nuclear envelope. The NPC is a modular assembly of ~500 individual proteins, called nucleoporins or nups. Most scaffolding nups are organized in two multimeric subcomplexes, the Nup84 or Y complex and the Nic96 or inner ring complex. Working in S. cerevisiae, and to study the assembly of these two essential subcomplexes, we here develop a set of twelve nanobodies that recognize seven constituent nucleoporins of the Y and Nic96 complexes. These nanobodies all bind specifically and with high affinity. We present structures of several nup-nanobody complexes, revealing their binding sites. Additionally, constitutive expression of the nanobody suite in S. cerevisiae detect accessible and obstructed surfaces of the Y complex and Nic96 within the NPC. Overall, this suite of nanobodies provides a unique and versatile toolkit for the study of the NPC.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation

The first step of RAF activation involves binding to active RAS, resulting in the recruitment of RAF to the plasma membrane. To understand the molecular details of RAS-RAF interaction, we present crystal structures of wild-type and oncogenic mutants of KRAS complexed with the RAS-binding domain (RBD) and the membrane-interacting cysteine-rich domain (CRD) from the N-terminal regulatory region of RAF1. Our structures reveal that RBD and CRD interact with each other to form one structural entity in which both RBD and CRD interact extensively with KRAS. Mutations at the KRAS-CRD interface result in a significant reduction in RAF1 activation despite only a modest decrease in binding affinity. Combining our structures and published data, we provide a model of RAS-RAF complexation at the membrane, and molecular insights into RAS-RAF interaction during the process of RAS-mediated RAF activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Massively parallel reporter assays and mouse transgenic assays provide correlated and complementary information about neuronal enhancer activity

High-throughput massively parallel reporter assays (MPRAs) and phenotype-rich in vivo transgenic mouse assays are two potentially complementary ways to study the impact of noncoding variants associated with psychiatric diseases. Here, we investigate the utility of combining these assays. Specifically, we carry out an MPRA in induced human neurons on over 50,000 sequences derived from fetal neuronal ATAC-seq datasets and enhancers validated in mouse assays. We also test the impact of over 20,000 variants, including synthetic mutations and 167 common variants associated with psychiatric disorders. We find a strong and specific correlation between MPRA and mouse neuronal enhancer activity. Four out of five tested variants with significant MPRA effects affected neuronal enhancer activity in mouse embryos. Mouse assays also reveal pleiotropic variant effects that could not be observed in MPRA. Our work provides a catalog of functional neuronal enhancers and variant effects and highlights the effectiveness of combining MPRAs and mouse transgenic assays.

Kosicki, Michael↗
DOE OSTI2022

The flying spider-monkey tree fern genome provides insights into fern evolution and arborescence

To date, little is known about the evolution of fern genomes, with only two small genomes published from the heterosporous Salviniales. Here we assembled the genome of Alsophila spinulosa, known as the flying spider-monkey tree fern, onto 69 pseudochromosomes. The remarkable preservation of synteny, despite resulting from an ancient whole-genome duplication over 100 million years ago, is unprecedented in plants and probably speaks to the uniqueness of tree ferns. Our detailed investigations into stem anatomy and lignin biosynthesis shed new light on the evolution of stem formation in tree ferns. We identified a phenolic compound, alsophilin, that is abundant in xylem, and we provided the molecular basis for its biosynthesis. Finally, analysis of demographic history revealed two genetic bottlenecks, resulting in rapid demographic declines of A. spinulosa. The A. spinulosa genome fills a crucial gap in the plant genomic landscape and helps elucidate many unique aspects of tree fern biology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Two novel fish paralogs provide insights into the Rid family of imine deaminases active in pre-empting enamine/imine metabolic damage

Reactive Intermediate Deaminase (Rid) protein superfamily includes eight families among which the RidA is conserved in all domains of life. RidA proteins accelerate the deamination of the reactive 2-aminoacrylate (2AA), an enamine produced by some pyridoxal phosphate (PLP)-dependent enzymes. 2AA accumulation inhibits target enzymes with a detrimental impact on fitness. As a consequence of whole genome duplication, teleost fish have two ridA paralogs, while other extant vertebrates contain a single-copy gene. We investigated the biochemical properties of the products of two paralogs, identified in Salmo salar. Ss RidA-1 and Ss RidA-2 complemented the growth defect of a Salmonella enterica ridA mutant, an in vivo model of 2AA stress. In vitro, both proteins hydrolyzed 2-imino acids (IA) to keto-acids and ammonia. Ss RidA-1 was active on IA derived from nonpolar amino acids and poorly active or inactive on IA derived from other amino acids tested. In contrast, SsRidA-2 had a generally low catalytic efficiency, but showed a relatively higher activity with IA derived from L-Glu and aromatic amino acids. The crystal structures of Ss RidA-1 and Ss RidA-2 provided hints of the remarkably different conformational stability and substrate specificity. Overall, Ss RidA-1 is similar to the mammalian orthologs whereas SsRidA-2 displays unique properties likely generated by functional specialization of a duplicated ancestral gene.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

CubeSat constellations provide enhanced crop phenology and digital agricultural insights using daily leaf area index retrievals

Satellite remote sensing has great potential to deliver on the promise of a data-driven agricultural revolution, with emerging space-based platforms providing spatiotemporal insights into precision-level attributes such as crop water use, vegetation health and condition and crop response to management practices. Using a harmonized collection of high-resolution Planet CubeSat, Sentinel-2, Landsat-8 and additional coarser resolution imagery from MODIS and VIIRS, we exploit a multi-satellite data fusion and machine learning approach to deliver a radiometrically calibrated and gap-filled time-series of daily leaf area index (LAI) at an unprecedented spatial resolution of 3 m. The insights available from such high-resolution CubeSat-based LAI data are demonstrated through tracking the growth cycle of a maize crop and identifying observable within-field spatial and temporal variations across key phenological stages. Daily LAI retrievals peaked at the tasseling stage, demonstrating their value for fertilizer and irrigation scheduling. An evaluation of satellite-based retrievals against field-measured LAI data collected from both rain-fed and irrigated fields shows high correlation and captures the spatiotemporal development of intra- and inter-field variations. Novel agricultural insights related to individual vegetative and reproductive growth stages were obtained, showcasing the capacity for new high-resolution CubeSat platforms to deliver actionable intelligence for precision agricultural and related applications.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design

Abstract Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.

Science & Technology - Other Topics↗
DOE OSTI2021

Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates

Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder caused by an expanded poly-glutamine (polyQ) tract in the mutant huntingtin (mHTT) protein. The formation and topology of filamentous mHTT inclusions in the brain (hallmarks of HD implicated in neurotoxicity) remain elusive. Using cryo-electron tomography and subtomogram averaging, here we show that mHTT exon 1 and polyQ-only aggregates in vitro are structurally heterogenous and filamentous, similar to prior observations with other methods. Yet, we find filaments in both types of aggregates under ~2 nm in width, thinner than previously reported, and regions forming large sheets. In addition, our data show a prevalent subpopulation of filaments exhibiting a lumpy slab morphology in both aggregates, supportive of the polyQ core model. This provides a basis for future cryoET studies of various aggregated mHTT and polyQ constructs to improve their structure-based modeling as well as their identification in cells without fusion tags.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Failure of molecular dynamics to provide appropriate structures for quantum mechanical description of the aqueous chloride ion charge-transfer-to-solvent ultraviolet spectrum

The lowest band in the charge-transfer-to-solvent ultraviolet absorption spectrum of aqueous chloride ion is studied by experiment and computation. Interestingly, the experiments indicate that at concentrations up to at least 0.25 M, where calculations indicate ion pairing to be significant, there is no notable effect of ionic strength on the spectrum. The experimental spectra are fitted to aid comparison with computations. Classical molecular dynamic simulations are carried out on dilute aqueous Cl - , Na + , and NaCl, producing radial distribution functions in reasonable agreement with experiment and, for NaCl, clear evidence of ion pairing. Clusters are extracted from the simulations for quantum mechanical excited state calculations. Accurate ab initio coupled-cluster benchmark calculations on a small number of representative clusters are carried out and used to identify and validate an efficient protocol based on time-dependent density functional theory. The latter is used to carry out quantum mechanical calculations on thousands of clusters. The resulting computed spectrum is in excellent agreement with experiment for the peak position, with little influence from ion pairing, but is in qualitative disagreement on the width, being only about half as wide. It is concluded that simulation by classical molecular dynamics fails to provide an adequate variety of structures to explain the experimental CTTS spectrum of aqueous Cl - .

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

MiniDAQ-3: Providing concurrent independent subdetector data-taking on CMS production DAQ resources

The data acquisition (DAQ) of the Compact Muon Solenoid (CMS) experiment at CERN, collects data for events accepted by the Level-1 Trigger from the different detector systems and assembles them in an event builder prior to making them available for further selection in the High Level Trigger, and finally storing the selected events for offline analysis. In addition to the central DAQ providing global acquisition functionality, several separate, so-called “MiniDAQ” setups allow operating independent data acquisition runs using an arbitrary subset of the CMS subdetectors. During Run 2 of the LHC, MiniDAQ setups were running their event builder and High Level Trigger applications on dedicated resources, separate from those used for the central DAQ. This cleanly separated MiniDAQ setups from the central DAQ system, but also meant limited throughput and a fixed number of possible MiniDAQ setups. In Run 3, MiniDAQ-3 setups share production resources with the new central DAQ system, allowing each setup to operate at the maximum Level-1 rate thanks to the reuse of the resources and network bandwidth. Configuration management tools had to be significantly extended to support the synchronization of the DAQ configurations needed for the various setups. We report on the new configuration management features and on the first year of operational experience with the new MiniDAQ-3 system.

Amoiridis, Vassileios↗
DOE OSTI2020

A Customizable Metric to Provide a Comprehensive Picture of the Mobility Potential of a Location

Accessibility in a geo-spatial context refers to the ease of reaching a variety of opportunities from a given location. Accessibility theories (and resulting metrics) have traditionally focused on quantifying access to specific opportunities (such as jobs), or focused on specific modes (such as car, bike, etc.). Such approaches often fall short of providing a comprehensive picture of the true accessibility potential of a location as a combination of multiple modes to multiple types of destinations. Addressing this drawback, a novel metric labeled the ‘Mobility Energy Productivity (MEP) Metric’ was developed at the National Renewable Energy Laboratory to quantify the mobility potential of a location to connect people to goods, services, and employment using a variety of modes, while accounting for time, energy, and affordability. The MEP metric has been integrated with advance travel behavior models to compute the changes in mobility potential for various future scenarios, such as introduction of automated vehicles, and/or electric vehicles—but does so at the aggregate, or average-citizen level. The MEP in its initial iteration is not customized to the particular socio-economic contingents, or even to an individual whose modal availability or pattern of trip making may substantially differ from the average. Addressing this gap, this research effort extends the MEP framework from a static state to a more tailored and dynamic state, one in which an individual, or group can customize the metric for their unique characteristics, such as modes, activity patterns, and time-of-day preferences. The extended MEP metric framework can now be integrated to assess the customized mobility energy productivity of an individual.

ADVANCED PROPULSION SYSTEMS,ENERGY PLANNING, POLIC↗
DOE OSTI2024

Photovoltaic effect on silicon–alumina–ferromagnet tunnel junction providing insights about spin-dependent molecular spintronics solar cells

The study focuses on the observation of the photovoltaic (PV) effect on Si/AlOx/FM semiconductor–insulator–ferromagnetic metal (SIFM) structure. Utilization of ~10 nm NiFe film as the top ferromagnet (FM) layer was permeable for sufficient light radiation necessary for reaching the silicon substrate for the generation of electron–hole pairs upon photoexcitation. The effect of light intensity and magnetic field was studied on the SIFM’s PV response. We also investigated the role of silicon doping and the AlOx tunnel barrier between Si and FM in exploring suitable band bending necessary for separating the electron–hole pairs. Increasing the dopant density in Si and a damaged AlOx tunnel barrier quenched the PV effect. Ferromagnet/Insulator/Ferromagnet (FMIFM) was also studied to gain deeper mechanistic insights into the spin-dependent photovoltaic effect observed on FM/AlOx/FM tunnel junction-based molecular spintronics devices. Bridging of magnetic molecules between the Si and FM electrodes of SIFM increased the overall device current by establishing additional parallel conduction channels along with the AlOx tunnel barrier. However, SIFM with molecular conduction channels did not produce a PV effect. This study reported the PV effect on well-designed SIFM and opened possibilities for exploring new systems. More importantly, this paper provided insights into the role of molecule-induced exchange coupling in transforming an ordinary, cheap, and widely available ferromagnet into a semiconductor-like material capable of showing PV.

14 SOLAR ENERGY↗
DOE OSTI2021

Public data from three US states provide new insights into well integrity

Significance There are over 900,000 active oil and gas wells in the United States. Estimates of the percentage of these wells that leak during their lifetime have been limited by data availability. We mined publicly available records from state regulatory databases and synthesized the results of various well testing methods into a uniform dataset that describes the integrity of 105,031 wells. Our analysis of the dataset provides insight into regional well leakage frequencies in three US states (Colorado, New Mexico, and Pennsylvania), spatial and temporal leakage trends among vertical and directional wells, and the characteristics of leaked fluids. Our findings demonstrate the value of statewide well testing programs and highlight the challenges of interpreting disparate interjurisdictional well testing data.

04 OIL SHALES AND TAR SANDS↗
DOE OSTI2023

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Do quasar X-ray and UV flux measurements provide a useful test of cosmological models?

ABSTRACT The recent compilation of quasar (QSO) X-ray and ultraviolet (UV) flux measurements include QSOs that appear to not be standardizable via the X-ray luminosity and UV luminosity (LX–LUV) relation and so should not be used to constrain cosmological model parameters. Here, we show that the largest of seven sub-samples in this compilation, the SDSS-4XMM QSOs that contribute about 2/3 of the total QSOs, have LX–LUV relations that depend on the cosmological model assumed and also on redshift, and is the main cause of the similar problem discovered earlier for the full QSO compilation. The second and third biggest sub-samples, the SDSS-Chandra and XXL QSOs that together contribute about 30 per cent of the total QSOs, appear standardizable, but provide only weak constraints on cosmological parameters that are not inconsistent with the standard spatially flat ΛCDM model or with constraints from better-established cosmological probes.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

The crystal structure of bacteriophage λ RexA provides novel insights into the DNA binding properties of Rex-like phage exclusion proteins

Abstract RexA and RexB function as an exclusion system that prevents bacteriophage T4rII mutants from growing on Escherichia coli λ phage lysogens. Recent data established that RexA is a non-specific DNA binding protein that can act independently of RexB to bias the λ bistable switch toward the lytic state, preventing conversion back to lysogeny. The molecular interactions underlying these activities are unknown, owing in part to a dearth of structural information. Here, we present the 2.05-Å crystal structure of the λ RexA dimer, which reveals a two-domain architecture with unexpected structural homology to the recombination-associated protein RdgC. Modelling suggests that our structure adopts a closed conformation and would require significant domain rearrangements to facilitate DNA binding. Mutagenesis coupled with electromobility shift assays, limited proteolysis, and double electron–electron spin resonance spectroscopy support a DNA-dependent conformational change. In vivo phenotypes of RexA mutants suggest that DNA binding is not a strict requirement for phage exclusion but may directly contribute to modulation of the bistable switch. We further demonstrate that RexA homologs from other temperate phages also dimerize and bind DNA in vitro. Collectively, these findings advance our mechanistic understanding of Rex functions and provide new evolutionary insights into different aspects of phage biology.

Biochemistry & Molecular Biology↗
DOE OSTI2024

Reaction-diffusion modeling provides insights into biophysical carbon-concentrating mechanisms in land plants

Carbon-concentrating mechanisms (CCMs) have evolved numerous times in photosynthetic organisms. They elevate the concentration of CO 2 around the carbon-fixing enzyme rubisco, thereby increasing CO 2 assimilatory flux and reducing photorespiration. Biophysical CCMs, like the pyrenoid-based CCM (PCCM) of Chlamydomonas reinhardtii or carboxysome systems of cyanobacteria, are common in aquatic photosynthetic microbes, but in land plants appear only among the hornworts. To predict the likely efficiency of biophysical CCMs in C 3 plants, we used spatially resolved reaction-diffusion models to predict rubisco saturation and light use efficiency. We found that the energy efficiency of adding individual CCM components to a C 3 land plant is highly dependent on the permeability of lipid membranes to CO 2 , with values in the range reported in the literature that are higher than those used in previous modeling studies resulting in low light use efficiency. Adding a complete PCCM into the leaf cells of a C 3 land plant was predicted to boost net CO 2 fixation, but at higher energetic costs than those incurred by photorespiratory losses without a CCM. Two notable exceptions were when substomatal CO 2 levels are as low as those found in land plants that already use biochemical CCMs and when gas exchange is limited, such as with hornworts, making the use of a biophysical CCM necessary to achieve net positive CO 2 fixation under atmospheric CO 2 levels. This provides an explanation for the uniqueness of hornworts' CCM among land plants and the evolution of pyrenoids multiple times.

Kaste, Joshua A. M.↗