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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Orientation-selected micro-pillar compression of additively manufactured 316L stainless steels: Comparison of as-manufactured, annealed, and proton-irradiated variants

In this work, irradiation response and deformation mechanisms of additively manufactured (AM) 316L stainless steel were studied by atomic scale characterization and micro-pillar compression. The AM 316L stainless steels were fabricated by direct energy deposition, a laser-based additive manufacturing process. Irradiation with 2 MeV protons at 360°C was performed to create ~1.8 displacements-per-atom (dpa) damage in AM 316L. Deformation behaviors of the as-manufactured, annealed, and proton-irradiated variants were studied, focusing on the effects of manufacturing-induced pores, residual stress, and irradiation-introduced defects (dislocation loops and voids). Micro-pillars were prepared from grains of pre-selected orientation, avoiding contributions of grain boundaries and allowing determination of resolved shear stress on {111} glide planes. Transmission electron microscopy was used to characterize the pre- and post-deformation microstructure. It was found that in the as-manufactured alloy variant, moving dislocations were the major deformation carrier, with noticeable blocking by fabrication-induced pores, In the annealed variant, hardness was reduced, and deformation was also accomplished by dislocation gliding. In the proton-irradiated variant, significant twinning was observed. Comparing measured resolved shear stress and predicted critical stress for dislocation dissociation, we conclude that irradiation hardening became high enough to activate twinning. Therefore, the deformation mechanism changes from dislocation gliding to twinning. The study is important for both processing optimization and performance evaluation of AM alloys for reactor applications.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Effect of epitope variant co-delivery on the depth of CD8 T cell responses induced by HIV-1 conserved mosaic vaccines

To stop the HIV-1 pandemic, vaccines must induce responses capable of controlling vast HIV-1 variants circulating in the population as well as those evolved in each individual following transmission. Numerous strategies have been proposed, of which the most promising include focusing responses on the vulnerable sites of HIV-1 displaying the least entropy among global isolates and using algorithms that maximize vaccine match to circulating HIV-1 variants by vaccine cocktails of optimized complementing sequences. In this study, we investigated CD8 T cell responses induced by a bi-valent mosaic of highly conserved HIVconsvX regions delivered by a combination of simian adenovirus ChAdOx1 and poxvirus MVA. We compared partially and fully mono- and bi-valent prime-boost regimens and their ability to elicit T cells recognizing natural epitope variants using an interferon-g enzyme-linked immunospot (ELISPOT) assay. We used 11 well-defined CD8 T cell epitopes in two mouse haplotypes and, for each epitope, assessed recognition of the two vaccine forms together with the other most frequent epitope variants in the HIV-1 database. We conclude that for the magnitude and depth of epitope recognition, CD8 T cell responses benefitted in most comparisons from the combined bi-valent mosaic and envisage the main advantage of the bi-valent vaccine during its deployment to diverse populations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Structural Insights into Low and High Recalcitrance Natural Poplar Variants Using Neutron and X-ray Scattering

Here, we used small-angle neutron scattering (SANS) and wide-angle X-ray scattering (WAXS) to study two Populus trichocarpa variants, GW-11012 and BESC-316, with lignin contents of 17.8 and 23.2%, respectively, to understand why the low lignin variant has increased sugar release during liquid hot water (LHW) pretreatment. SANS showed differences in cell wall polymer arrangement in the variants. In GW-11012, the cellulose microfibrils were similar in size to BESC-316 but were not equally spaced and lignin was aggregated rather than homogenously interspersed with other matrix co-polymers. However, after LHW pretreatments, the SANS profiles of the pretreated variants were almost indistinguishable, indicating that the nanoscale structural features could not adequately explain the increased sugar release observed in GW-11012. WAXS analysis revealed higher cellulose crystallinity and larger crystallite size in native and pretreated GW-11012. However, the most significant difference was that the crystallite orientation was approximately 2-fold higher in GW-11012. This suggests that higher crystallite orientation may be favorable for the action of processive cellulases leading to increased sugar release from GW-11012. Our study shows that there is a complex interplay between cell wall polymers during their deposition resulting in changes in lignin distribution and cellulose structure, highlighting the importance of investigating plant cell wall architecture across multiple length scales.

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

Chemoproteogenomic stratification of the missense variant cysteinome

Abstract Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics—a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues—with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.

Desai, Heta (ORCID:0000000343621707)↗
DOE OSTI2026

Non-coding structural variants disrupt FOXG1 transcriptional regulation in early neurodevelopment

The FOXG1 transcription factor is a crucial regulator of embryonic brain development. Pathogenic FOXG1 variants cause FOXG1 syndrome. Although structural variants in the non-coding region downstream of FOXG1 have been reported in 38 individuals with similar characteristics, the regulatory pathomechanisms remain unknown. Here, we identify two non-coding structural variants in individuals with FOXG1 syndrome-like features, allowing us to delineate a ~ 124 kb commonly affected regulatory region. Using epigenomic profiling and in vivo enhancer assays, we characterize and validate regulatory elements within the commonly affected regulatory region and wider FOXG1 TAD. We see strong activation of previously validated forebrain enhancers, and identify an enhancer cluster and progenitor-specific enhancer region that are strongly activated during forebrain-directed neural progenitor cell differentiation, a process in which FOXG1 is an important regulator. Perturbation of these elements results in varying degrees of reduced FOXG1 transcription in forebrain neural progenitor cells and in population shifts within these cells, while removal of the TAD boundary leads to aberrant expression of the neighbouring PRKD1 gene. Our findings characterize enhancer and architectural elements essential for proper FOXG1 transcription during neurodevelopment, therefore improving variant interpretation in this region.

Hamerlinck, Lisa↗
DOE OSTI2022

Unsupervised learning of ferroic variants from atomically resolved STEM images

An approach for the analysis of atomically resolved scanning transmission electron microscopy data with multiple ferroic variants in the presence of imaging non-idealities and chemical variabilities based on a rotationally invariant variational autoencoder (rVAE) is presented. We show that an optimal local descriptor for the analysis is a sub-image centered at specific atomic units, since materials and microscope distortions preclude the use of an ideal lattice as a reference point. The applicability of unsupervised clustering and dimensionality reduction methods is explored and is shown to produce clusters dominated by chemical and microscope effects, with a large number of classes required to establish the presence of rotational variants. Comparatively, the rVAE allows extraction of the angle corresponding to the orientation of ferroic variants explicitly, enabling straightforward identification of the ferroic variants as regions with constant or smoothly changing latent variables and sharp orientational changes. This approach allows further exploration of the chemical variability by separating the rotational degrees of freedom via rVAE and searching for remaining variability in the system. The code used in this article is available at https://github.com/saimani5/ferroelectric_domains_rVAE.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2024

Evolving dual-trait EPSP synthase variants using a synthetic yeast selection system

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) functions in the shikimate pathway which is responsible for the production of aromatic amino acids and precursors of other essential secondary metabolites in all plant species. EPSPS is also the molecular target of the herbicide glyphosate. While some plant EPSPS variants have been characterized with reduced glyphosate sensitivity and have been used in biotechnology, the glyphosate insensitivity typically comes with a cost to catalytic efficiency. Thus, there exists a need to generate additional EPSPS variants that maintain both high catalytic efficiency and high glyphosate tolerance. Here, we create a synthetic yeast system to rapidly study and evolve heterologous EPSP synthases for these dual traits. Using known EPSPS variants, we first validate that our synthetic yeast system is capable of recapitulating growth characteristics observed in plants grown in varying levels of glyphosate. Next, we demonstrate that variants from mutagenesis libraries with distinct phenotypic traits can be isolated depending on the selection criteria applied. By applying strong dual-trait selection pressure, we identify a notable EPSPS mutant after just a single round of evolution that displays robust glyphosate tolerance (K i of nearly 1 mM) and improved enzymatic efficiency over the starting point (~2.5 fold). Finally, we show the crystal structure of corn EPSPS and the top resulting mutants and demonstrate that certain mutants have the potential to outperform previously reported glyphosate-resistant EPSPS mutants, such as T102I and P106S (denoted as TIPS), in whole-plant testing. Altogether, this platform helps explore the trade-off between glyphosate resistance and enzymatic efficiency.

Science & Technology - Other Topics↗
DOE OSTI2021

Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles

Efforts to determine why new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants demonstrate improved fitness have been limited to analyzing mutations in the spike (S) protein with the use of S-pseudotyped particles. In this study, we show that SARS-CoV-2 virus-like particles (SC2-VLPs) can package and deliver exogenous transcripts, enabling analysis of mutations within all structural proteins and at multiple steps in the viral life cycle. In SC2-VLPs, four nucleocapsid (N) mutations found universally in more-transmissible variants independently increased messenger RNA delivery and expression ~10-fold, and in a reverse genetics model, the serine-202→arginine (S202R) and arginine-203→methionine (R203M) mutations each produced >50 times as much virus. SC2-VLPs provide a platform for rapid testing of viral variants outside of a biosafety level 3 setting and demonstrate N mutations and particle assembly to be mechanisms that could explain the increased spread of variants, including B.1.617.2 (Delta, which contains the R203M mutation).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Domestic Sales Mix of Plug-In Electric Vehicles by Trim Variant and Vehicle Characteristics

As plug-in electric vehicles (PEVs) take up a larger share of the United States vehicle market, their variety increases as well. Since many electric vehicle manufacturers offer multiple PEV trim variants, the distribution of vehicle characteristics such as battery capacity, all-electric range, electricity consumption, and curb weight cannot be determined by sales data alone. Sales data and vehicle registration data were analyzed to quantify and map the trim variant distribution of PEV models from nine automakers. With this information, we quantify national sales-weighted characteristics of fourteen different models over ten years, including battery capacity, fuel economy, and vehicle weight. We find a positive correlation between share of all-wheel drive variants for Tesla vehicles and average annual snowfall, and general uniformity nationwide in other vehicle characteristics. The estimated trim variant distributions will be useful in informing decisions regarding materials recycling and EV impact on the energy grid, and this study found that the total installed battery capacity in PEV in the U.S. was 76 GWh through 2020.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2023

US National Institutes of Health Prioritization of SARS-CoV-2 Variants

Since late 2020, SARS-CoV-2 variants have regularly emerged with competitive and phenotypic differences from previously circulating strains, sometimes with the potential to escape from immunity produced by prior exposure and infection. The Early Detection group is one of the constituent groups of the US National Institutes of Health National Institute of Allergy and Infectious Diseases SARS-CoV-2 Assessment of Viral Evolution program. Here, the group uses bioinformatic methods to monitor the emergence, spread, and potential phenotypic properties of emerging and circulating strains to identify the most relevant variants for experimental groups within the program to phenotypically characterize. Since April 2021, the group has prioritized variants monthly. Prioritization successes include rapidly identifying most major variants of SARS-CoV-2 and providing experimental groups within the National Institutes of Health program easy access to regularly updated information on the recent evolution and epidemiology of SARS-CoV-2 that can be used to guide phenotypic investigations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Global estimates of the fitness advantage of SARS-CoV-2 variant Omicron

Abstract New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness over both time and space. In this paper we extend the tools available for estimating the selection strength for new SARS-CoV-2 variants to a hierarchical, mixed-effects, renewal equation model. This formulation allows us to estimate selection effects at the global level while incorporating both measured and unmeasured heterogeneity among countries. Applying this model to the spread of Omicron in forty countries, we find evidence for very strong but very heterogeneous selection effects. To test whether this heterogeneity is explained by differences in the immune landscape, we considered several measures of vaccination rates and recent population-level infection as covariates, finding moderately strong, statistically significant effects. We also found a significant positive correlation between the selection advantage of Delta and Omicron at the country level, suggesting that other region-specific explanatory variables of fitness differences do exist. Our method is implemented in the Stan programming language, can be run on standard consumer-grade computing resources, and will be straightforward to apply to future variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display

The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.

SARS-CoV-2↗
DOE OSTI2023

Pressured cytotoxic T cell epitope strength among SARS-CoV-2 variants correlates with COVID-19 severity

Heterogeneity in susceptibility among individuals to COVID-19 has been evident through the pandemic worldwide. Cytotoxic T lymphocyte (CTL) responses generated against pathogens in certain individuals are known to impose selection pressure on the pathogen, thus driving emergence of new variants. In this study, we probe the role played by host genetic heterogeneity in terms of HLA-genotypes in determining differential COVID-19 severity in patients. We use bioinformatic tools for CTL epitope prediction to identify epitopes under immune pressure. Using HLA-genotype data of COVID-19 patients from a local cohort, we observe that the recognition of pressured epitopes from the parent strain Wuhan-Hu-1 correlates with COVID-19 severity. We also identify and rank list HLA-alleles and epitopes that offer protectivity against severe disease in infected individuals. Finally, we shortlist a set of 6 pressured and protective epitopes that represent regions in the viral proteome that are under high immune pressure across SARS-CoV-2 variants. In conclusion, identification of such epitopes, defined by the distribution of HLA-genotypes among members of a population, could potentially aid in prediction of indigenous variants of SARS-CoV-2 and other pathogens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Comparative Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Variants in the Ferret Model

The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans necessitates evaluation of variants for enhanced virulence and transmission. We used the ferret model to perform a comparative analysis of four SARS-CoV-2 strains, including an early pandemic isolate from the United States (WA1), and representatives of the Alpha, Beta, and Delta lineages. While Beta virus was not capable of pronounced replication in ferrets, WA1, Alpha, and Delta viruses productively replicated in the ferret upper respiratory tract, despite causing only mild disease with no overt histopathological changes. Strain-specific transmissibility was observed; WA1 and Delta viruses transmitted in a direct contact setting, whereas Delta virus was also capable of limited airborne transmission. Viral RNA was shed in exhaled air particles from all inoculated animals but was highest for Delta virus. Prior infection with SARS-CoV-2 offered varied protection against reinfection with either homologous or heterologous variants. Notable genomic variants in the spike protein were most frequently detected following WA1 and Delta virus infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Mutations of Omicron Variant at the Interface of the Receptor Domain Motif and Human Angiotensin-Converting Enzyme-2

The most recent Omicron variant of SARS-CoV-2 has caused global concern and anxiety. The only thing certain about this strain, with a large number of mutations in the spike protein, is that it spreads quickly, seems to evade immune defense, and mitigates the benefits of existing vaccines. Based on the ultra-large-scale ab initio computational modeling of the receptor binding motif (RBM) and the human angiotensin-converting enzyme-2 (ACE2) interface, we provide the details of the effect of Omicron mutations at the fundamental atomic scale level. In-depth analysis anchored in the novel concept of amino acid-amino acid bond pair units (AABPU) indicates that mutations in the Omicron variant are connected with (i) significant changes in the shape and structure of AABPU components, together with (ii) significant increase in the positive partial charge, which facilitates the interaction with ACE2. We have identified changes in bonding due to mutations in the RBM. The calculated bond order, based on AABPU, reveals that the Omicron mutations increase the binding strength of RBM to ACE2. Our findings correlate with and are instrumental to explain the current observations and can contribute to the prediction of next potential new variant of concern.

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

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Structural comparison of allophycocyanin variants reveals the molecular basis for their spectral differences

Abstract Allophycocyanins are phycobiliproteins that absorb red light and transfer the energy to the reaction centers of oxygenic photosynthesis in cyanobacteria and red algae. Recently, it was shown that some allophycocyanins absorb far-red light and that one subset of these allophycocyanins, comprising subunits from the ApcD4 and ApcB3 subfamilies (FRL-AP), form helical nanotubes. The lowest energy absorbance maximum of the oligomeric ApcD4-ApcB3 complexes occurs at 709 nm, which is unlike allophycocyanin (AP; ApcA-ApcB) and allophycocyanin B (AP-B; ApcD-ApcB) trimers that absorb maximally at ~ 650 nm and ~ 670 nm, respectively. The molecular bases of the different spectra of AP variants are presently unclear. To address this, we structurally compared FRL-AP with AP and AP-B, performed spectroscopic analyses on FRL-AP, and leveraged computational approaches. We show that among AP variants, the α-subunit constrains pyrrole ring A of its phycocyanobilin chromophore to different extents, and the coplanarity of ring A with rings B and C sets a baseline for the absorbance maximum of the chromophore. Upon oligomerization, the α-chromophores of all AP variants exhibit a red shift of the absorbance maximum of ~ 25 to 30 nm and band narrowing. We exclude excitonic coupling in FRL-AP as the basis for this red shift and extend the results to discuss AP and AP-B. Instead, we attribute these spectral changes to a conformational alteration of pyrrole ring D, which becomes more coplanar with rings B and C upon oligomerization. This study expands the molecular understanding of light-harvesting attributes of phycobiliproteins and will aid in designing phycobiliproteins for biotechnological applications.

Gisriel, Christopher J.↗
DOE OSTI2023

MALDI-MS screening of microbial colonies with isomer resolution to select fatty acid desaturase variants

Creating controlled lipid unsaturation locations in oleochemicals can be a key to many bioengineered products. However, evaluating the effects of modifications to the acyl-ACP desaturase on lipid unsaturation is not currently amenable to high-throughput assays, limiting the scale of redesign efforts to <200 variants. Here, we report a rapid MS assay for profiling the positions of double bonds on membrane lipids produced by Escherichia coli colonies after treatment with ozone gas. By MS measurement of the ozonolysis products of Δ6 and Δ8 isomers of membrane lipids from colonies expressing recombinant Thunbergia alata desaturase, we screened a randomly mutagenized library of the desaturase gene at 5 s per sample. Two variants with altered regiospecificity were isolated, indicated by an increase in 16:1 Δ8 proportion. We also demonstrated the ability of these desaturase variants to influence the membrane composition and fatty acid distribution of E. coli strains deficient in the native acyl-ACP desaturase gene, fabA. Lastly, we used the fabA deficient chassis to concomitantly express a non-native acyl- ACP desaturase and a medium-chain thioesterase from Umbellularia californica, demonstrating production of only saturated free fatty acids.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗