SEARCH · Search NASA

Results for “Bounded domains”

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.

SourceResearch connectionFrom yearThrough year

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

At least 73 records · Page 4

All sources NASA NTRS DOE OSTI

DOE OSTI2021

Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A

Staphylococcus aureus causes reiterative and chronic persistent infections. This can be explained by the formidable ability of this pathogen to escape immune surveillance mechanisms. Cells of S. aureus display the abundant staphylococcal protein A (SpA). SpA binds to immunoglobulin (Ig) molecules and coats the bacterial surface to prevent phagocytic uptake. SpA also binds and cross-links variable heavy 3 (V H 3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific V H 3-IgM via a mechanism requiring CD4 + T cell help. SpA binding to antibodies is mediated by the N-terminal Ig-binding domains (IgBDs). The so-called region X, uncharacterized LysM domain, and C-terminal LPXTG sorting signal for peptidoglycan attachment complete the linear structure of the protein. Here, we report that both the LysM domain and the LPXTG motif sorting signal are required for the B cell superantigen activity of SpA in a mouse model of infection. SpA molecules purified from staphylococcal cultures are sufficient to exert B cell superantigen activity and promote immunoglobulin secretion as long as they carry intact LysM and LPXTG motif domains with bound peptidoglycan fragments. The LysM domain binds the glycan chains of peptidoglycan fragments, whereas the LPXTG motif is covalently linked to wall peptides lacking glycan. These findings emphasize the complexity of SpA interactions with B cell receptors.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting

Abstract The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states. In the nucleotide-free state, Rep68 forms a heptameric complex around DNA, with three origin-binding domains (OBDs) bound to the Rep-binding element sequence, while three remaining OBDs form transient dimers with them. The AAA+ domains form an open ring without interactions between subunits and DNA. We hypothesize that the heptameric structure is crucial for loading Rep68 onto double-stranded DNA. The ATPγS complex shows that only three subunits associate with the nucleotide, leading to a conformational change that promotes the formation of both intersubunit and DNA interactions. Moreover, three phenylalanine residues in the AAA+ domain induce a steric distortion in the DNA. Our study provides insights into how an SF3 helicase assembles on DNA and provides insights into the DNA melting process.

Jaiswal, Rahul↗

NASA NTRS1992

Palinspastic reconstruction of southeastern California and southwestern Arizona for the middle Miocene

A paleogeographic reconstruction of southeastern California and southwestern Arizona at 10 Ma was made based on available geologic and geophysical data. Clockwise rotation of 39 deg was reconstructed in the eastern Transverse Ranges, consistent with paleomagnetic data from late Miocene volcanic rocks, and with slip estimates for left-lateral faults within the eastern Transverse Ranges and NW-trending right lateral faults in the Mojave Desert. This domain of rotated rocks is bounded by the Pinto Mountain fault on the north. In the absence of evidence for rotation of the San Bernardino Mountains or for significant right slip faults within the San Bernardino Mountains, the model requires that the late Miocene Pinto Mountain fault become a thrust fault gaining displacement to the west. The Squaw Peak thrust system of Meisling and Weldon may be a western continuation of this fault system. The Sheep Hole fault bounds the rotating domain on the east. East of this fault an array of NW-trending right slip faults and south-trending extensional transfer zones has produced a basin and range physiography while accumulating up to 14 km of right slip. This maximum is significantly less than the 37.5 km of right slip required in this region by a recent reconstruction of the central Mojave Desert. Geologic relations along the southern boundary of the rotating domain are poorly known, but this boundary is interpreted to involve a series of curved strike slip faults and non-coaxial extension, bounded on the southeast by the Mammoth Wash and related faults in the eastern Chocolate Mountains. Available constraints on timing suggest that Quaternary movement on the Pinto Mountain and nearby faults is unrelated to the rotation of the eastern Transverse Ranges, and was preceded by a hiatus during part of Pliocene time which followed the deformation producing the rotation. The reconstructed Clemens Well fault in the Orocopia Mountains, proposed as a major early Miocene strand of the San Andreas fault, projects eastward towards Arizona, where early Miocene rocks and structures are continuous across its trace. The model predicts a 14 deg clockwise rotation and 55 km extension along the present trace of the San Andreas fault during late Miocene and early Pliocene time. Palinspastic reconstructions of the San Andreas system based on this proposed reconstruction may be significantly modified from current models.

Richard, Stephen M.↗

NASA NTRS2010

Interactions of Ku70/80 with Double-Strand DNA: Energetic, Dynamics, and Functional Implications

Space radiation is a proficient inducer of DNA damage leading to mutation, aberrant cell signaling, and cancer formation. Ku is among the first responding proteins in nucleus to recognize and bind the DNA double strand breaks (DSBs) whenever they are introduced. Once loaded Ku works as a scaffold to recruit other repair factors of non-homologous end joining and facilitates the following repair processes. The crystallographic study of the Ku70/80 heterodimer indicate the core structure of this protein shows virtually no conformational change after binding with DNA. To investigate the dynamical features as well as the energetic characteristics of Ku-DNA binding, we conduct multi-nanosecond molecular dynamics simulations of a modeled Ku70/80 structure and several complexes with two 24-bp DNA duplexes. Free energy calculations show significant energy differences between the complexes with Ku bound at DSBs and those with Ku associated at an internal site of a chromosome. The results also reveal detailed interactions between different nucleotides and the amino acids along the DNA-binding cradle of Ku, indicating subtle binding preference of Ku at specific DNA sequences. The covariance matrix analyses along the trajectories demonstrate the protein is stimulated to undergo correlated motions of different domains once bound to DNA ends. Additionally, principle component analyses identify these low frequency collective motions suitable for binding with and translocation along duplex DNA. It is proposed that the modification of dynamical properties of Ku upon binding with DSBs may provide a signal for the further recruitment of other repair factors such as DNA-PKcs, XLF, and XRCC4.

Hu, Shaowen↗

DOE OSTI2025

Structures of a synthetic antibody selected against and bound to the C‐terminal domain of Clostridium perfringens enterotoxin

Abstract Clostridium perfringensenterotoxin (CpE) causes cytotoxic gastrointestinal disease in mammalian epithelium by binding membrane protein receptors called claudins. Claudins direct the formation of cell/cell tight junctions through oligomerization and govern the transport of molecules between individual cells. CpE binds claudins through its C‐terminal domain (cCpE) and induces cytotoxicity through its N‐terminal domain. The non‐toxic cCpE is a useful tool to study claudins, tight junctions, and for translational applications, such as increasing the permeability of restrictive tissues like the blood–brain barrier or selective targeting of claudin overexpressing cancers. Conversely, there are no specialized molecular tools to study CpE or cCpE, or to modulate or inhibit their functions. We previously reported the development of synthetic antigen‐binding fragments (sFabs) that bind cCpE, and low‐resolution structures of them bound to claudin/cCpE complexes. Here, we determine high‐resolution structures of sFab COP‐2 bound to cCpE using X‐ray crystallography and cryogenic electron microscopy. The structures and biophysical findings provide the mechanism of COP‐2 binding to cCpE and the molecular determinants driving their interactions. These insights can advance the design of new antibody‐based tools from our COP‐2 scaffold to study or alter cCpE function and give rise to a “Trojan horse” strategy that exploits cCpE's tight junction barrier disrupting function to selectively deliver conjugated therapeutics through normally impermeable tissues.

Biochemistry & Molecular Biology↗

NASA NTRS2001

Improving Simulated Annealing by Replacing Its Variables with Game-Theoretic Utility Maximizers

The game-theory field of Collective INtelligence (COIN) concerns the design of computer-based players engaged in a non-cooperative game so that as those players pursue their self-interests, a pre-specified global goal for the collective computational system is achieved as a side-effect. Previous implementations of COIN algorithms have outperformed conventional techniques by up to several orders of magnitude, on domains ranging from telecommunications control to optimization in congestion problems. Recent mathematical developments have revealed that these previously developed algorithms were based on only two of the three factors determining performance. Consideration of only the third factor would instead lead to conventional optimization techniques like simulated annealing that have little to do with non-cooperative games. In this paper we present an algorithm based on all three terms at once. This algorithm can be viewed as a way to modify simulated annealing by recasting it as a non-cooperative game, with each variable replaced by a player. This recasting allows us to leverage the intelligent behavior of the individual players to substantially improve the exploration step of the simulated annealing. Experiments are presented demonstrating that this recasting significantly improves simulated annealing for a model of an economic process run over an underlying small-worlds topology. Furthermore, these experiments reveal novel small-worlds phenomena, and highlight the shortcomings of conventional mechanism design in bounded rationality domains.

Wolpert, David H.↗

DOE OSTI2020

The effects of stress, temperature and facet structure on growth of { 10 1 ¯ 2 } twins in Mg: a molecular dynamics and phase field study

The present study focuses on the roles of structure, stress and temperature on the mobility of facets bounding twin domains and on the overall impact on the growth kinetics of { 10 1 ¯ 2 } twins in Mg. We first use molecular dynamics simulations (MD) to study the relationship between interface structures, stress, temperature and mobility. As facets can exhibit distinct atomic scale structures, we also quantify the effect of stress relaxation mediated by misfit dislocations on the mobility of the basal-prismatic interface. The information gathered for ten different facets is used to calibrate an anisotropic phase field model predicting the effects of temperature and stress on the kinetics and shape of a growing { 10 1 ¯ 2 } 3D twin, by comparison with MD data. The comparative analysis suggests that, as compared to simulations of individual facets, the effective mobility of facets can be significantly different during growth of a 3D twin. This can be attributed to the complex three-dimensional internal stress state of the twin and to coupling in facet motion triggered by facet junctions. As such, by directly fitting both the twin growth kinetics and morphology as predicted by MD for different stresses and temperatures, we can identify a limited set of rate-limiting facets that control twin growth and morphology, and measure their effective mobility.

36 MATERIALS SCIENCE↗

DOE OSTI2022

A mass conservative, well balanced, tangency preserving and energy decaying method for the shallow water equations on a sphere

Here a fully discrete surface finite element method is proposed for solving the viscous shallow water equations in a bounded Lipschitz domain on the sphere based on a general triangular mesh. The method consists of a modified Crank–Nicolson method in time and a Galerkin surface finite element method in space for the fluid thickness H and the fluid velocity u. A finite element space tangential to the sphere at all finite element nodes is proposed to approximate the fluid velocity u. The proposed method has second-order accuracy in time and first-order accuracy in space, and preserves mass conservation, well balancedness, tangency of velocity to the sphere, and energy decay. Numerical experiments are presented to illustrate the accuracy of the proposed method and the preservation of the physical properties, including mass conservation, well balancedness, and energy decay. A numerical simulation of ocean mesoscale activity on a circular basin with a continental shelf is provided.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2024

Neutron skins: A perspective from dispersive optical models

An overview of neutron skin predictions obtained using an empirical nonlocal dispersive optical model (DOM) is presented. The DOM links both scattering and bound-state experimental data through a subtracted dispersion relation which allows for fully consistent, data-informed predictions for nuclei where such data exist. Large skins were predicted for both 48 Ca ( R$^{48}_{skin}$ = 0.25 ± 0.023 fm in 2017) and 208 Pb (R$^{208}_{skin}$) = 0.25 ± 0.05 fm in 2020). Whereas the DOM prediction in 208 Pb is within 1σ of the subsequent PREX-2 measurement, the DOM prediction in 48 Ca is over 2σ larger than the thin neutron skin resulting from CREX. From the moment it was revealed, the thin skin in 48 Ca has puzzled the nuclear-physics community as no adequate theories simultaneously predict both a large skin in 208 Pb and a small skin in 48 Ca. The DOM is unique in its ability to treat both structure and reaction data on the same footing, providing a unique perspective on this R skin puzzle. It appears vital that more neutron data be measured in both the scattering and bound-state domain for 48 Ca to clarify the situation.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

NASA NTRS1993

Statistical dependence of albedo and cloud cover on sea surface temperature for two tropical marine stratocumulus regions

The relationship between sea surface temperature (SST) and albedo or cloud cover is examined for two tropical regions with high values of cloud radiative forcing and persistent marine stratocumulus (mSc)-one off the west coast of Peru, the other off the west coast of Angola. The data span five years, from December 1984 to November 1989. Albedos are from the Earth Radiation Budget Experiment (ERBE), cloud covers are from the International Satellite Cloud Climatology Project (ISCCP), and SSTS are from the Climate Analysis Center. Negative correlation coefficients between albedo and SST are found to be about -0.8 when the seasonal variation of the entire dataset is analyzed. The interannual variation and the spatial variation of individual months also yields correlation coefficients that are negative. The correlation between cloud cover and SST is found to be similar to but weaker than the correlation between albedo and SST, suggesting a decrease in cloud amount and a decrease in cloud albedo with increasing SST for these regions. The corresponding albedo sensitivity averages -0.018/K with local values reaching -0.04/K. These findings are valid from 19 C to 25 C for the Peru mSc and 22 C to 27 C for the Angola mSc. These temperatures approximately bound the domains over which mSc is the prevalent cloud type within each region. These results imply a potential positive feedback to global warming by marine stratocumulus that ranges from approximately 0.14 W/sq m/K to approximately 1 W/sq m/K, depending on whether or not our results apply to all marine stratocumulus. While these values are uncertain to at least +/- 50%, the sensitivity of albedo to sea surface temperature in the present climate may serve as a useful diagnostic tool in monitoring the performance of global climate models.

Oreopoulos, Lazaros↗

NASA NTRS2020

Evaluating Precipitation Features and Rainfall Characteristics in a Multi‐Scale Modeling Framework

Cloud and precipitation systems are simulated with a multi‐scale modeling framework (MMF) and compared over the Tropics and Subtropics against the Tropical Rainfall Measuring Mission (TRMM) Radar‐defined Precipitation Features (RPFs) product. A methodology, in close analogy to the TRMM RPFs, is developed to produce simulated precipitation features (PFs) from the output of the embedded two‐dimensional (2D) cloud‐resolving models (CRMs) within an MMF. Despite the limitations of 2D CRMs, the simulated population distribution, horizontal and vertical structure of PFs, and the geographical location and local rainfall contribution of mesoscale convective systems (MCSs) are in good agreement with the TRMM observations. However, some model discrepancies are found and can be identified and quantified within the PF distributions. Using model biases in relative population and rainfall contributions, PFs can be characterized into four size categories: small, medium to large, very large, and extremely large. Four different major mechanisms might account for the model biases in each different category: (1) the two‐dimensionality of the CRMs, (2) a positive convection‐wind‐evaporation feedback loop, (3) an artificial dynamic constraint in a bounded CRM domain with cyclic boundaries, and (4) the limited CRM domain size. The second and fourth mechanisms tend to contribute to the excessive tropical precipitation biases commonly found in most MMFs, whereas the other mechanisms reduce rainfall contributions from small and very large PFs. MMF sensitivity experiments with various CRM domain sizes and grid spacings showed that larger domains (higher resolutions) tend to shift PF populations toward larger (smaller) sizes.

Jiun-Dar Chern↗

DOE OSTI2021

Functional characterization of a cellulose synthase, CtCESA1, from the marine red alga Calliarthron tuberculosum (Corallinales)

In land plants and algae, cellulose is important for strengthening cell walls and preventing breakage due to physical forces. Though our understanding of cellulose production by cellulose synthases (CESAs) has seen significant advances for several land plant and bacterial species, functional characterization of this fundamental protein is absent in red algae. Here we identify CESA gene candidates in the calcifying red alga Calliarthron tuberculosum using sequence similarity-based approaches, and elucidate their phylogenetic relationship with other CESAs from diverse taxa. One gene candidate, CtCESA1, was closely related to other putative red algal CESA genes. To test if CtCESA1 encoded a true cellulose synthase, CtCESA1 protein was expressed and purified from insect and yeast expression systems. CtCESA1 showed glucan synthase activity in glucose tracer assays. CtCESA1 activity was relatively low when compared with plant and bacterial CESA activity. In an in vitro assay, a predicted N-terminal starch-binding domain from CtCESA1 bound red algal floridean starch extracts, representing a unique domain in red algal CESAs not present in CESAs from other lineages. When the CtCESA1 gene was introduced into Arabidopsis thaliana cesa mutants, the red algal CtCESA1 partially rescued the growth defects of the primary cell wall cesa6 mutant, but not cesa3 or secondary cell wall cesa7 mutants. A fluorescently tagged CtCESA1 localized to the plasma membrane in the Arabidopsis cesa6 mutant background. This study presents functional evidence validating the sequence annotation of red algal CESAs. Furthermore, the relatively low activity of CtCESA1, partial complementation in Arabidopsis, and presence of unique protein domains suggest that there are probably functional differences between the algal and land plant CESAs.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1986

Reduced conservatism in stability robustness bounds by state transformation

This note addresses the issue of 'conservatism' in the time domain stability robustness bounds obtained by the Liapunov approach. A state transformation is employed to improve the upper bounds on the linear time-varying perturbation of an asymptotically stable linear time-invariant system for robust stability. This improvement is due to the variance of the conservatism of the Liapunov approach with respect to the basis of the vector space in which the Liapunov function is constructed. Improved bounds are obtained, using a transformation, on elemental and vector norms of perturbations (i.e., structured perturbations) as well as on a matrix norm of perturbations (i.e., unstructured perturbations). For the case of a diagonal transformation, an algorithm is proposed to find the 'optimal' transformation. Several examples are presented to illustrate the proposed analysis.

Yedavalli, R. K.↗

DOE OSTI2023

Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230

Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine candidate. Prior understanding of functional epitopes on Pfs230 is based on two monoclonal antibodies (mAbs) with moderate transmission-reducing activity (TRA), elicited from subunit immunization. Here, we screened the B cell repertoire of two naturally exposed individuals possessing serum TRA and identified five potent mAbs from sixteen Pfs230 domain-1-specific mAbs. Structures of three potent and three low-activity antibodies bound to Pfs230 domain 1 revealed four distinct epitopes. Highly potent mAbs from natural infection recognized a common conformational epitope that is highly conserved across P. falciparum field isolates, while antibodies with negligible TRA derived from natural infection or immunization recognized three distinct sites. Our study provides molecular blueprints describing P. falciparum TRA, informed by contrasting potent and non-functional epitopes elicited by natural exposure and vaccination.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Constellation's best estimate alternate source term methodology overview

Safety analyses for a nuclear power plants need to consider postulated accidents that results in at risk of accidental release of radiation. The regulations require plant specific safety analysis reports to include an evaluation of the requirements of 10CFR50.67. Such a safety analysis report mandates limits such that calculated radiological consequences relative to certain dose locations do not exceed a total effective dose equivalent (TEDE) limits following a postulated release of radioactivity. Calculations are performed to estimate the radiological consequences, in terms of dose, to people and equipment to ensure the estimated doses are within the prescribed limits. Analysis should demonstrate, with reasonable assurance, that these prescribed limits are complied with. Conventional methodologies utilize conservative approaches to address lack of uncertainty quantification in the utilized approaches, methods, and/or inputs. These built-in excess conservatisms often result in compounding effects and hence overly conservative results in the estimated radiological consequences, which leads to inaccurate margin evaluation for operation and accident mitigation. Therefore, evaluating accurate dose consequences is needed for both operational and safety reasons. The research documented in this paper provides an overview of Constellation's Best Estimate Alternate Source Term (BEAST) Methodology. BEAST methodology relies upon the use of realistic yet bounding input distributions for key analysis parameters, which replaces use of conservative deterministic singular inputs that bound overall analysis domain. This approach enables evaluating a more accurate accident analysis response, while enabling a bounding licensing basis envelope via more accurate quantification of uncertainty in the application. Therefore, built-in margin for a given scenario is more accurately evaluated.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

NASA NTRS2012

Bounding the Failure Probability Range of Polynomial Systems Subject to P-box Uncertainties

This paper proposes a reliability analysis framework for systems subject to multiple design requirements that depend polynomially on the uncertainty. Uncertainty is prescribed by probability boxes, also known as p-boxes, whose distribution functions have free or fixed functional forms. An approach based on the Bernstein expansion of polynomials and optimization is proposed. In particular, we search for the elements of a multi-dimensional p-box that minimize (i.e., the best-case) and maximize (i.e., the worst-case) the probability of inner and outer bounding sets of the failure domain. This technique yields intervals that bound the range of failure probabilities. The offset between this bounding interval and the actual failure probability range can be made arbitrarily tight with additional computational effort.

Crespo, Luis G.↗

DOE OSTI2020

Mechanistic insights from structure of Mycobacterium smegmatis topoisomerase I with ssDNA bound to both N- and C-terminal domains

Abstract Type IA topoisomerases interact with G-strand and T-strand ssDNA to regulate DNA topology. However, simultaneous binding of two ssDNA segments to a type IA topoisomerase has not been observed previously. We report here the crystal structure of a type IA topoisomerase with ssDNA segments bound in opposite polarity to the N- and C-terminal domains. Titration of small ssDNA oligonucleotides to Mycobacterium smegmatis topoisomerase I with progressive C-terminal deletions showed that the C-terminal region has higher affinity for ssDNA than the N-terminal active site. This allows the C-terminal domains to capture one strand of underwound negatively supercoiled DNA substrate first and position the N-terminal domains to bind and cleave the opposite strand in the relaxation reaction. Efficiency of negative supercoiling relaxation increases with the number of domains that bind ssDNA primarily with conserved aromatic residues and possibly with assistance from polar/basic residues. A comparison of bacterial topoisomerase I structures showed that a conserved transesterification unit (N-terminal toroid structure) for cutting and rejoining of a ssDNA strand can be combined with two different types of C-terminal ssDNA binding domains to form diverse bacterial topoisomerase I enzymes that are highly efficient in their physiological role of preventing excess negative supercoiling in the genome.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Deuteron off-resonance rotating frame relaxation for the characterization of slow motions in rotating and static solid-state proteins

Here, we demonstrate the feasibility of deuterium solid-state NMR off-resonance rotating frame relaxation measurements for studies of slow motions in biomolecular solids. The pulse sequence, which includes adiabatic pulses for magnetization alignment, is illustrated for static and magic-angle spinning conditions away from rotary resonances. We apply the measurements for three systems with selective deuterium labels at methyl groups: a) a model compound, Fluorenylmethyloxycarbonyl methionine-D 3 amino acid, for which the principles of the measurements and corresponding motional modeling based on rotameric interconversions are demonstrated; b) amyloid-β 1-40 fibrils labeled at a single alanine methyl group located in the disordered N-terminal domain. This system has been extensively studied in prior work and here serves as a test of the method for complex biological systems. The essential features of the dynamics consist of large-scale rearrangements of the disordered N-terminal domain and the conformational exchange between the free and bound forms of the domain, the latter one due to transient interactions with the structured core of the fibrils. and c) a 15-residue helical peptide which belongs to the predicted α-helical domain near the N-terminus of apolipoprotein B. The peptide is solvated with triolein and incorporates a selectively labeled leucine methyl groups. The method permits model refinement, indicating rotameric interconversions with a distribution of rate constants.

59 BASIC BIOLOGICAL SCIENCES↗