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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 1,045 records · Page 58
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications

The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon–anticodon pairing

Modifications in the tRNA anticodon loop, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguanosine modification at guanine nucleotide 37 (m 1 G37) located in the anticodon loop andimmediately adjacent to the anticodon nucleotides 34, 35, 36. The absence of m 1 G37 in tRNA Pro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNA Pro bound to either cognate or slippery codons to determine how the m 1 G37 modification prevents mRNA frameshifting. The structures reveal that certain codon–anticodon contexts and the lack of m 1 G37 destabilize interactions of tRNA Pro with the P site of the ribosome, causing large conformational changes typically only seen during EF-G-mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how m 1 G37 stabilizes the interactions of tRNA Pro with the ribosome in the context of a slippery mRNA codon.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement

Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair. Here, we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored to this core by the N-terminus of Sth1. Our cryo-EM analysis of RSC bound to a nucleosome core particle shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of the Rsc8 SWIRM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

The connectome of the adult Drosophila mushroom body provides insights into function

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory, and activity regulation. Here, we identify new components of the MB circuit in Drosophila , including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

Li, Feng↗
DOE OSTI2021

Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis

Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of Neisseria that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin (Lf), and in providing protection against the cationic antimicrobial peptide lactoferricin (Lfcn). While previous studies support a dual role for LbpB, exactly how these ligands interact with LbpB has remained unknown. Here, we present the structures of LbpB from N. meningitidis and N. gonorrhoeae in complex with human holo-Lf, forming a 1:1 complex and confirmed by size-exclusion chromatography small-angle X-ray scattering. LbpB consists of N- and C-lobes with the N-lobe interacting extensively with the C-lobe of Lf. Our structures provide insight into LbpB’s preference towards holo-Lf, and our mutagenesis and binding studies show that Lf and Lfcn bind independently. Our studies provide the molecular details for how LbpB serves to capture and preserve Lf in an iron-bound state for delivery to the membrane transporter LbpA for iron piracy, and as an antimicrobial peptide sink to evade host immune defenses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Deep learning-driven insights into super protein complexes for outer membrane protein biogenesis in bacteria

To reach their final destinations, outer membrane proteins (OMPs) of gram-negative bacteria undertake an eventful journey beginning in the cytosol. Multiple molecular machines, chaperones, proteases, and other enzymes facilitate the translocation and assembly of OMPs. These helpers usually associate, often transiently, forming large protein assemblies. They are not well understood due to experimental challenges in capturing and characterizing protein-protein interactions (PPIs), especially transient ones. Using AF2Complex, we introduce a high-throughput, deep learning pipeline to identify PPIs within the Escherichia coli cell envelope and apply it to several proteins from an OMP biogenesis pathway. Among the top confident hits obtained from screening ~1500 envelope proteins, we find not only expected interactions but also unexpected ones with profound implications. Subsequently, we predict atomic structures for these protein complexes. These structures, typically of high confidence, explain experimental observations and lead to mechanistic hypotheses for how a chaperone assists a nascent, precursor OMP emerging from a translocon, how another chaperone prevents it from aggregating and docks to a β-barrel assembly port, and how a protease performs quality control. This work presents a general strategy for investigating biological pathways by using structural insights gained from deep learning-based predictions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

New insight into the role of MMP14 in metabolic balance

Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14 KO litter fail to thrive due to disorder in metabolism.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1981

Insights into the gas dynamics in galaxies via a particle model

Techniques of rarefied gas dynamics are applied to the astrophysical problem of gas flow in disk galaxies. Historically, studies of the interstellar gas dynamics in spiral galaxies have assumed the medium could be regarded as both isothermal and continuous. However, it now appears that the gaseous interstellar medium may be better idealized as a rarefied gas or discrete system of interacting particles. Principal evidence for this is that the galaxies themselves exhibit a degree of disorder and raggedness that is characteristic of a rarefied gaseous system with a Knudsen number of approximately 0.02-0.2. In this paper a particle model for gas flow in a spiral galaxy is developed and some implications of the results are discussed. The results are compared to an analytical inviscid calculation to gain further physical insight.

Levinson, F. H.↗
NASA NTRS1992

Insights into software development in Japan

The interdependence of the U.S.-Japanese economies makes it imperative that we in the United States understand how business and technology developments take place in Japan. We can gain insight into these developments in software engineering by studying the context in which Japanese software is developed, the practices that are used, the problems encountered, the setting surrounding these problems, and the resolution of these problems. Context includes the technological and sociological characteristics of the software development environment, the software processes applied, personnel involved in the development process, and the corporate and social culture surrounding the development. Presented in this paper is a summary of results of a study that addresses these issues. Data for this study was collected during a three month visit to Japan where the author interviewed 20 software managers representing nine companies involved in developing software in Japan. These data are compared to similar data from the United States in which 12 managers from five companies were interviewed.

Duvall, Lorraine M.↗
NASA NTRS1997

Gamma-Ray Astrophysics: New Insight Into the Universe

During the 15 years that have passed since the first edition of this book was published, there has been a major increase in our knowledge of gamma-ray astronomy. Much of this advance arises from the extensive results that have been forthcoming from the Compton Gamma-Ray Observatory. There has been the discovery of a new class of gamma-ray objects, namely high-energy gamma- ray-emitting blazars, a special class of Active Galactic Nuclei, whose basic high-energy properties now seem to be understood. A much improved picture of our galaxy now exists in the frequency range of gamma rays. The question of whether cosmic rays are galactic or metagalactic now seems settled with certainty. Significant new information exists on the gamma-ray properties of neutron star pulsars, Seyfert galaxies, and gamma-ray bursts. Substantial new insight has been obtained on solar phenomena through gamma-ray observations. Hence, this seemed to be an appropriate time to write a new edition of this book to add the important scientific implications of these many new findings. The special importance of gamma-ray astrophysics had long been recognized by many physicists and astronomers, and theorists had pursued many aspects of the subject well before the experimental results began to become available. The slower development of the experimental side was not because of a lack of incentive, but due to the substantial experimental difficulties that had to be overcome. Thus, as the gamma-ray results became available in much greater number and detail, it was possible to build upon the theoretical work that already existed and to make substantial progress in the study of many of the phenomena involved. Consequently, a much better understanding of many of the astrophysical phenomena mentioned here and others is now possible. Our principal aims in writing this book are the same as they were for the first edition: to provide a text which describes the significance of gamma-ray astrophysics and to assemble in one place a treatment of gamma rays emitted from bodies in the solar i system, from objects in our galaxy, as well as from interactions between cosmic rays and the interstellar medium, and from beyond our galaxy. Thus, this book is intended for those in astrophysics who wish to have the opportunity to learn more about the evolving field of gamma-ray astronomy and its relationship to the high-energy, evolutionary processes occurring in the universe. The last three chapters of the book provide a general discussion of the experimental aspects of the field that seemed best treated together, separately from the astrophysical aspects of gamma-ray astronomy that are discussed in the first ten chapters.

Fichtel, Carl E.↗
NASA NTRS1999

Aerodynamic and Aeroelastic Insights using Eigenanalysis

This paper presents novel analytical results for eigenvalues and eigenvectors produced using discrete time aerodynamic and aeroelastic models. An unsteady, incompressible vortex lattice aerodynamic model is formulated in discrete time; the importance of several modeling parameters is examined. A detailed study is made of the behavior of the aerodynamic eigenvalues both in discrete and continuous time. The aerodynamic model is then incorporated into aeroelastic equations of motion. Eigenanalyses of the coupled equations produce stability results and modal characteristics which are valid for critical and non-critical velocities. Insight into the modeling and physics associated with aeroelastic system behavior is gained by examining both the eigenvalues and the eigenvectors. Potential pitfalls in discrete time model construction and analysis are examined.

Heeg, Jennifer↗
NASA NTRS1999

Addendum to Gamma-Ray Astrophysics: New Insight Into the Universe Second Edition (RP1386 - October 1997)

We have been encouraged by the positive reactions that we have received to the second edition of the publication Gamma-Ray Astrophysics, New Insight into the Universe, and therefore, wish to make a few additions. In this addendum there are three small parts: A. Comments on New Findings since October 1997, B. Figures, and C. Corrections. In part B, some of the figures that were in the book have been reproduced here in larger form so that they are easier to read. In part C, the corrections that have come to our attention since the original publication are included.

Fichtel, Carl E.↗
NASA NTRS2000

Large Grooves in the South Polar Layered Deposits: Insights from Spacecraft Data and Terrestrial Analogs

The Martian polar layered deposits (PLD) are probably the best source of information about the recent climate history of Mars, but their origin and the mechanisms of accumulation are still a mystery. The polar layers are sedimentary deposits that most planetary scientists believe are composed of water ice and varying amounts of wind-blown dust, although their composition is poorly constrained. Interpretation of the observed polar stratigraphy in terms of global climate changes is complicated by the significant difference in surface ages between the north and south PLD inferred from crater statistics. The study reported here was undertaken as part of the landing site selection effort for the Mars Polar Lander (MPL) and Deep Space 2 (DS2) missions that made use of all available data. We used Mariner 9, Viking, and Mars Global Surveyor images of the south PLD in the area accessible to MPL and DS2 to evaluate the topography and morphology of grooves, terraced layers, and other features. Here we report on results from grooves that appear to have been carved by strong winds. Because these features are found throughout the interior of the PLD, where MPL and DS2 were targeted to land, their topographic characteristics were judged as important input for landing site safety assessment. The characteristics of the grooves also provide constraints and insights into aeolian processes in the polar regions and the effects these have on PLD ablation. Our results indicate that these grooves do not represent landing hazards at the scale of the images (approx. 80 m/pixel). Their topography and shape do not seem correlated with south PLD layering. No Earth analog of suitable scale exists, although the grooves bear some resemblance to smaller terrestrial deflation hollows found in soft sediment and ice. Additional information is contained in original extended abstract.

Bridges, N. T.↗
NASA NTRS2001

New Insights into Tropospheric Ozone from Satellites and Soundings

The past 4-5 years have seen an unprecedented increase in tropospheric ozone (and related) observations thanks to focused campaigns, new satellite data, and to innovative approaches to climatology (commercial aircraft sampling, networks). The result has been new insights into the complex chemistry and dynamics affecting tropospheric ozone in the non-urban environment: global pollution, subtropical stratospheric folds, disturbances associated with the 1997 El-Nino. A synthesis based on selected examples of field and satellite data, much of it from Goddard's tropospheric work, will be presented.

Thompson, A.↗
NASA NTRS2001

Spectroscopy of Low Mass X-Ray Binaries: New Insights into Accretion

This project is to observe two low mass X-ray binaries, chosen for their X-ray brightness, low column density, and diversity of accretion behavior. The high spectral resolution of the RGS, the broad energy range and tremendous collecting power of EPIC, and simultaneous optical monitoring with the OM are particularly well-suited to these studies. observation of one of the two objects has taken place and the data were received in late November. The second object is yet to be observed. Over the next year we will: investigate the physical conditions of the emitting gas using emission and recombination line diagnostics to determine temperatures, densities, elemental abundances, and ionization structure; study the behavior of emission features as a function of binary orbit; and test and improve models of X-ray line emission developed by us over the past decade. We will gain insight on both the geometry of the accretion flow and on the evolutionary history of LMXBs.

DilVrtilek, Saeqa↗
NASA NTRS2002

Spectroscopy of Low Mass X-Ray Binaries: New Insights into Accretion

This project is to observe two low mass X-ray binaries, chosen for their X-ray brightness, low column density, and diversity of accretion behavior. The high spectral resolution of the RGS, the broad energy range and tremendous collecting power of EPIC, and simultaneous optical monitoring with the OM are particularly well-suited to these studies. The second of two objects was not observed until September of 2002. Data analysis for the new observation is underway. over the next year we will: investigate the physical conditions of the emitting gas using emission and recombination line diagnostics to determine temperatures, densities, elemental abundances, and ionization structure; study the behavior of emission features as a function of binary orbit; and test and improve models of X-ray line emission developed by us over the past decade. We will gain insight on both the geometry of the accretion flow and on the evolutionary history of LMXBs.

Vrtilek, Saeqa Dil↗
NASA NTRS2002

New Insights into the X-Ray Spectra of Heliumlike and Neonlike Ions

Recent measurements of the K-shell and L-shell x-ray spectra of highly charged helium- like and neonlike ions are presented that were performed on the Livermore electron beam ion traps and the Princeton tokamaks. These measurements provide new insights into collisional and indirect line formation processes, identifications of forbidden lines, and a new plasma line diagnostic of magnetic field strength.

IONS↗
NASA NTRS2003

Magma Reservoirs Feeding Giant Radiating Dike Swarms: Insights from Venus

Evidence of lateral dike propagation from shallow magma reservoirs is quite common on the terrestrial planets, and examination of the giant radiating dike swarm population on Venus continues to provide new insight into the way these complex magmatic systems form and evolve. For example, it is becoming clear that many swarms are an amalgamation of multiple discrete phases of dike intrusion. This is not surprising in and of itself, as on Earth there is clear evidence that formation of both magma reservoirs and individual giant radiating dikes often involves periodic magma injection. Similarly, giant radiating swarms on Earth can contain temporally discrete subswarms defined on the basis of geometry, crosscutting relationships, and geochemical or paleomagnetic signatures. The Venus data are important, however, because erosion, sedimentation, plate tectonic disruption, etc. on Earth have destroyed most giant radiating dike swarm's source regions, and thus we remain uncertain about the geometry and temporal evolution of the magma sources from which the dikes are fed. Are the reservoirs which feed the dikes large or small, and what are the implications for how the dikes themselves form? Does each subswarm originate from a single, periodically reactivated reservoir, or do subswarms emerge from multiple discrete geographic foci? If the latter, are these discrete foci located at the margins of a single large magma body, or do multiple smaller reservoirs define the character of the magmatic center as a whole? Similarly, does the locus of magmatic activity change with time, or are all the foci active simultaneously? Careful study of giant radiating dike swarms on Venus is yielding the data necessary to address these questions and constrain future modeling efforts. Here, using giant radiating dike swarms from the Nemesis Tessera (V14) and Carson (V43) quadrangles as examples, we illustrate some of the dike swarm focal region diversity observed on Venus and briefly explore some key implications for the questions framed above.

Grosfils, E. B.↗