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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 865 records · Page 48

Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site

The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics.

60 APPLIED LIFE SCIENCES↗

Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy

ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.

59 BASIC BIOLOGICAL SCIENCES↗

Drivers and implications of alternative routes to fuels decarbonization in net-zero energy systems

Energy transition scenarios are characterized by increasing electrification and improving efficiency of energy end uses, rapid decarbonization of the electric power sector, and deployment of carbon dioxide removal (CDR) technologies to offset remaining emissions. Although hydrocarbon fuels typically decline in such scenarios, significant volumes remain in many scenarios even at the time of net-zero emissions. While scenarios rely on different approaches for decarbonizing remaining fuels, the underlying drivers for these differences are unclear. Here we develop several illustrative net-zero systems in a simple structural energy model and show that, for a given set of final energy demands, assumptions about the use of biomass and CO2 sequestration drive key differences in how emissions from remaining fuels are mitigated. Limiting one resource may increase reliance on another, implying that decisions about using or restricting resources in pursuit of net-zero objectives could have significant tradeoffs that will need to be evaluated and managed.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.

60 APPLIED LIFE SCIENCES↗

A nanoscale photonic thermal transistor for sub-second heat flow switching

Abstract Control of heat flow is critical for thermal logic devices and thermal management and has been explored theoretically. However, experimental progress on active control of heat flow has been limited. Here, we describe a nanoscale radiative thermal transistor that comprises of a hot source and a cold drain (both are ~250 nm-thick silicon nitride membranes), which are analogous to the source and drain electrodes of a transistor. The source and drain are in close proximity to a vanadium oxide (VO x )-based planar gate electrode, whose dielectric properties can be adjusted by changing its temperature. We demonstrate that when the gate is located close ( < ~1 µm) to the source-drain device and undergoes a metal-insulator transition, the radiative heat transfer between the source and drain can be changed by a factor of three. More importantly, our nanomembrane-based thermal transistor features fast switching times ( ~ 500 ms as opposed to minutes for past three-terminal thermal transistors) due to its small thermal mass. Our experiments are supported by detailed calculations that highlight the mechanism of thermal modulation. We anticipate that the advances reported here will open new opportunities for designing thermal circuits or thermal logic devices for advanced thermal management.

42 ENGINEERING↗

Emerging multiscale insights on microbial carbon use efficiency in the land carbon cycle

Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

54 ENVIRONMENTAL SCIENCES↗

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders

Abstract Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN)cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. We evaluate enhancer activity for 59 elements using an in vivo transgenic assay and validate 44 (75%), demonstrating that single cell accessibility can be a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieve significant reduction in our variant search space and nominate candidate variants predicted to regulate known CCDD disease genesMAFB, PHOX2A, CHN1, andEBF3– as well as candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work delivers non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

Science & Technology - Other Topics↗

Large emissions of CO 2 and CH 4 due to active-layer warming in Arctic tundra

Climate warming may accelerate decomposition of Arctic soil carbon, but few controlled experiments have manipulated the entire active layer. To determine surface-atmosphere fluxes of carbon dioxide and methane under anticipated end-of-century warming, here we used heating rods to warm (by 3.8 °C) to the depth of permafrost in polygonal tundra in $Utqia\dot{g}vik$ (formerly Barrow), Alaska and measured fluxes over two growing seasons. We show that ecosystem respiration is ~30% higher in warmed plots than in control plots (0.99 μmol m -2 s -1 versus 0.67 μmol m -2 s -1 , p < 0.0001, n = 79). Additionally, the observed temperature sensitivity (Q 10 of 2.8) is higher than that imposed for soil in Earth system models or reported by arctic experiments warming only the surface. A shoulder-season warming experiment revealed that rapid snow melt, which is becoming a more common event, can result in large methane emissions that may have otherwise been oxidized to carbon dioxide. Thus, warming promotes greenhouse gas emissions from the whole, deepening active layer and may contribute to climate change amplification.

54 ENVIRONMENTAL SCIENCES↗

Structural basis for the subtype-selectivity of K Ca 2.2 channel activators

Small-conductance (K Ca 2.2) and intermediate-conductance (K Ca 3.1) Ca 2+ -activated K + channels are gated by a Ca 2+ -calmodulin dependent mechanism. NS309 potentiates the activity of both K Ca 2.2 and K Ca 3.1, while rimtuzalcap selectively activates K Ca 2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of NS309-bound K Ca 2.2 and K Ca 3.1, in addition to structures of rimtuzalcap-bound K Ca 2.2 and mutant K Ca 3.1_R355K. The different conformations of calmodulin and the cytoplasmic HC helices in the two channels underlie the subtype-selectivity of rimtuzalcap for K Ca 2.2. NS309 binds to pre-existing pockets in both channels, while the bulkier rimtuzalcap binds in an induced-fit pocket in K Ca 2.2 requiring conformational changes. In K Ca 2.2, calmodulin’s N-lobes are sufficiently far apart to enable conformational changes to accommodate either NS309 or rimtuzalcap. In K Ca 3.1, calmodulin’s N-lobes are closer to each other and constrained by K Ca 3.1’s HC helices, which allows binding of NS309 but not rimtuzalcap. Replacement of arginine-355 in K Ca 3.1’s HB helix with lysine (K Ca 3.1_R355K) allows the binding of rimtuzalcap and renders the mutant channel sensitive to rimtuzalcap. These structures provide a framework for structure-based drug design targeting K Ca 2.2 channels.

Nam, Young-Woo [Chapman Univ., Irvine, CA (United ↗

Pushing the frontiers in climate modelling and analysis with machine learning

Climate modelling and analysis are facing new demands to enhance projections and climate information. Here, in this study, we argue that now is the time to push the frontiers of machine learning beyond state-of-the-art approaches, not only by developing machine-learning-based Earth system models with greater fidelity, but also by providing new capabilities through emulators for extreme event projections with large ensembles, enhanced detection and attribution methods for extreme events, and advanced climate model analysis and benchmarking. Utilizing this potential requires key machine learning challenges to be addressed, in particular generalization, uncertainty quantification, explainable artificial intelligence and causality. This interdisciplinary effort requires bringing together machine learning and climate scientists, while also leveraging the private sector, to accelerate progress towards actionable climate science.

54 ENVIRONMENTAL SCIENCES↗

Towards an open model intercomparison platform for integrated assessment models scenarios

The majority of scenarios in the IPCC database are generated by integrated assessment models (IAMs) and come from model intercomparison projects. However, the way in which the current model intercomparison projects are organized is not open to all IAM teams worldwide. Here we propose a transparent and inclusive platform that is open to anyone with an IAM regarding protocols development, scenario submissions and results evaluation. We discuss the challenges of this approach, particularly human resources and financial support. Here, we identify diversity in the level of model capability and quality of model output as possibly critical issues. Despite such challenges, the IAM community and its scientific activities can improve and benefit from the proposed platform, ultimately contributing to better climate policymaking.

IAM↗

Genome expansion and lineage-specific genetic innovations in the forest pathogenic fungi Armillaria

Armillaria species are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes via rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analysed the genomes of four Armillaria species and performed RNA sequencing and quantitative proteomic analysis on the invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion in Armillaria, affecting several pathogenicity-related genes, lignocellulose-degrading enzymes and lineage-specific genes expressed during rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of both fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and share cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms of Armillaria might have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.

59 BASIC BIOLOGICAL SCIENCES↗

Historical and Future Learning for the New Era of Multi-Terawatt Photovoltaics

Solar photovoltaics (PV) is entering a new era of multi-terawatt deployment, with 2 TW already in service and more than 75 TW predicted in many scenarios by 2050. This next era has been enabled by over five decades of cumulative advances in PV module cost reduction, performance and reliability. The current scale of deployment also introduces new needs, opportunities and challenges. In this Perspective we frame a path forwards based on learning, broadly defined as a combination of expansion of knowledge and advances through research and development, experience and collaboration. We discuss historical topics where learning has driven PV deployment until now, and emerging areas that are required to sustain high levels of future deployment. We expect progress to continue in terms of module price, performance and reliability, driven by advances in PV cell and module design, the emergence of tandem devices and increased focus on extending module lifetimes. Large-scale deployment also means large-scale sustainability and responsibility. We therefore posit that additional metrics, such as the impact on global CO2 emissions, resource consumption and design for reuse and recycling, will become increasingly important to the PV industry and provide opportunities for further learning.

14 SOLAR ENERGY↗

Emergent temperature sensitivity of soil organic carbon driven by mineral associations

Abstract Soil organic matter decomposition and its interactions with climate depend on whether the organic matter is associated with soil minerals. However, data limitations have hindered global-scale analyses of mineral-associated and particulate soil organic carbon pools and their benchmarking in Earth system models used to estimate carbon cycle–climate feedbacks. Here we analyse observationally derived global estimates of soil carbon pools to quantify their relative proportions and compute their climatological temperature sensitivities as the decline in carbon with increasing temperature. We find that the climatological temperature sensitivity of particulate carbon is on average 28% higher than that of mineral-associated carbon, and up to 53% higher in cool climates. Moreover, the distribution of carbon between these underlying soil carbon pools drives the emergent climatological temperature sensitivity of bulk soil carbon stocks. However, global models vary widely in their predictions of soil carbon pool distributions. We show that the global proportion of model pools that are conceptually similar to mineral-protected carbon ranges from 16 to 85% across Earth system models from the Coupled Model Intercomparison Project Phase 6 and offline land models, with implications for bulk soil carbon ages and ecosystem responsiveness. To improve projections of carbon cycle–climate feedbacks, it is imperative to assess underlying soil carbon pools to accurately predict the distribution and vulnerability of soil carbon.

54 ENVIRONMENTAL SCIENCES↗