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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 1,189 records · Page 66
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Pan-H7 influenza human antibody virus neutralization depends on avidity and steric hindrance

H7N9 avian influenza virus is a zoonotic influenza virus of public health concern, with a 39% mortality rate in humans. H7N9-specific prevention or treatments for humans have not been approved. We previously isolated a human monoclonal antibody (mAb) designated H7-235 that broadly reacts to diverse H7 viruses and neutralizes H7N9 viruses in vitro. Here, we report the crystal structure of H7 HA1 bound to the fragment antigen-binding region (Fab) of recombinant H7-235 (rH7-235). The crystal structure revealed that rH7-235 recognizes residues near but outside of the receptor binding site (RBS). Nevertheless, the rH7-235 IgG potently inhibits hemagglutination mediated by H7N9 viruses due to avidity effect and Fc steric hindrance. This mAb prophylactically protects mice against weight loss and death caused by challenge with lethal H7N9 viruses in vivo. rH7-235 mAb neutralizing activity alone is sufficient for protection when used at a high dose in a prophylactic setting. This study provides insights into mechanisms of viral neutralization by protective, broadly reactive anti-H7 antibodies, informing the rational design of therapeutics and vaccines against H7N9 influenza virus.

Research & Experimental Medicine↗
DOE OSTI2020

The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription

β- and γ-herpesviruses include the oncogenic human viruses Kaposi’s sarcoma-associated virus (KSHV) and Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV), which is a significant cause of congenital disease. Near the end of their replication cycle, these viruses transcribe their late genes in a manner distinct from host transcription. Late gene transcription requires six virally encoded proteins, one of which is a functional mimic of host TATA-box-binding protein (TBP) that is also involved in recruitment of RNA polymerase II (Pol II) via unknown mechanisms. Here, we applied biochemical protein interaction studies together with electron microscopy-based imaging of a reconstituted human preinitiation complex to define the mechanism underlying Pol II recruitment. These data revealed that the herpesviral TBP, encoded by ORF24 in KSHV, makes a direct protein-protein contact with the C-terminal domain of host RNA polymerase II (Pol II), which is a unique feature that functionally distinguishes viral from cellular TBP. The interaction is mediated by the N-terminal domain (NTD) of ORF24 through a conserved motif that is shared in its β- and γ-herpesvirus homologs. Thus, these herpesviruses employ an unprecedented strategy in eukaryotic transcription, wherein promoter recognition and polymerase recruitment are facilitated by a single transcriptional activator with functionally distinct domains.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Biomanufacturing and bioprocessing of lunar regolith

Microbial biomanufacturing is important to accelerate lunar construction because it can leverage lunar material and waste streams as feedstocks to create a circular production system. In-space bio-mining and biomanufacturing using moon and asteroidal source material will enable the creation of infrastructure, produce industrial fuels and lubricants, and enable recovery of actinides and rare-earth elements (REEs) present in trace concentrations. Moreover, biomanufacturing in closed-loop systems (recycling and reuse of resources toward the establishment of a circular economy) will enable long-term lunar activities by recycling waste (CO 2 , gray water) and producing oxygen and biomaterials. Our response focuses on the use of lunar regolith and waste streams as feedstocks for protein and microbial-enabled biomining and bioprocessing to extract actinides and REEs, and to create biocomposites for lunar infrastructure. We envision an enclosed process that initiates with (1a) extracting actinides and REEs from lunar regolith using immobilized proteins, followed by (1b) creating biocomposites from the post-extracted lunar regolith for infrastructure, and (1c) cultivating diatoms and other microalgae on waste streams to harvest silica shells for incorporating into biocomposites and to generate O 2 for human respiration and/or producing refinable feedstocks. LLNL has significant expertise in all three processes and provides facilities, personnel, and expertise at the intersection of metal (lanthanide, actinide, transition) separations, purifications, biohydrometallurgy, radiobiochemistry, synthetic and systems biology, and materials science and engineering. Importantly, all three processes are relatively well-studied for Earth-based workflows and can be derisked for demonstration on the lunar surface by 2029.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Likeness: a toolkit for connecting the social fabric of place to human dynamics

The ability to produce richly-attributed synthetic populations is key for understanding human dynamics, responding to emergencies, and preparing for future events, all while protecting individual privacy. The Likeness toolkit accomplishes these goals with a suite of Python packages: pymedm/pymedm\_legacy, livelike, and actlike. This production process is initialized in pymedm (or pymedm\_legacy) that utilizes census microdata records as the foundation on which disaggregated spatial allocation matrices are built. The next step, performed by livelike, is the generation of a fully autonomous agent population attributed with hundreds of demographic census variables. The agent population synthesized in livelike is then attributed with residential coordinates in actlike based on block assignment and, finally, allocated to an optimal daytime activity location via the street network. We present a case study in Knox County, Tennessee, synthesizing 30 populations of public K–12 school students \& teachers and allocating them to schools. Validation of our results shows they are highly promising by replicating reported school enrollment and teacher capacity with a high degree of fidelity.

Tuccillo, Joe↗
DOE OSTI2021

Vadose and Saturated Zone Flow and Transport Calculations for the Active Trenches of the Low-Level Burial Grounds, Hanford Site, Washington

The purpose of the fate and transport modeling described in this environmental calculation file (ECF) is to evaluate the impacts to groundwater associated with waste disposal operations at Mixed Waste Low-Level Burial Ground (LLBG) Trenches 31 and 34 to satisfy requirements in DOE O 435.1, Radioactive Waste Management. The model integrates the flow and transport in the vadose zone beneath the active trenches with the saturated zone downgradient of the trenches to predict the radionuclide concentration at the point of assessment (POA). DOE M 435.1-1, Radioactive Waste Management Manual, defines the POA as the point of highest projected dose or concentration beyond a 100 m (328 ft) buffer zone surrounding the disposed waste. The modeling is conducted in accordance with the DOE G 435.1, Implementation Guide for Use with DOE M 435.1-1, performance assessment (PA) guidelines. The modeling involves evaluation of the groundwater concentrations and radionuclide arrival times during the 1,000-year compliance and 10,000-year sensitivity-uncertainty periods per DOE O 435.1 and DOE M 435.1. This analysis does not consider radionuclide release during facility operations, only the post-closure impacts of the radionuclides to the environment. The evaluation of potential radiological dose to groundwater receptors caused by releases from a closed facility containing radioactive waste typically includes the following: (1) Release of radionuclides from that facility (2) Transport of those radionuclides through the environment, and (3) Exposure to humans to environmental concentration levels of those radionuclides The fate and transport three-dimensional (3D) model analysis involves the post-closure impacts to the environment of the technetium-99, iodone-129, and uranium (all isotopes in the waste). The residual inventory estimates include several radionuclides, but technetium-99 is typically responsible for almost all of the beta-gamma dose equivalent associated with groundwater (water resources) protection per 40 CFR 141, “National Primary Drinking Water Regulations” (e.g., see the results in WCH-520, Performance Assessment of Environmental Restoration Disposal Facility, Hanford Site, Washington; hereinafter referred to as the ERDF PA), and iodone-129 can also be a significant dose contributor for some waste (e.g., RPP-RPT-59958, Performance Assessment for the Integrated Disposal Facility, Hanford Site, Washington; hereinafter referred to as the IDF PA). Uranium does not typically factor significantly into the impacts to groundwater, even during the 10,000-year sensitivity-uncertainty period, but always remains of interest as a contaminant. This ECF does not address vadose and saturated zone modeling for Trench 94 of the 200 East Area LLBG. Current information confirms the validity of the low corrosion rate of the naval reactor plant carbon steel (HY-80), and the even lower corrosion rate of the nickel-iron-chromium alloy reactor vessel (Inconel Alloy 600) presented in DOE/EIS-0259, Final Environmental Impact Statement on the Disposal of Decommissioned, Defueled Cruiser, Ohio Class, and Los Angeles Class Naval Reactor Plants. Based on these low corrosion rates, the time to breach the reactor vessel to allow release of radionuclides from the activated metal of the reactor vessel internal structure is at least 10,000 years. This time to breach precludes the need to evaluate the vadose and saturated zone transport of contaminants released from the reactor compartment disposal packages in the 200 East Area LLBGs PA (CP-63826, Waste Release Model Package Report for the Active Trenches of the Low-Level Burial Grounds, Hanford Site, Washington).

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2026

Interactions Between Climate Policy and Technology-influenced Travel Behavior: Mitigating Induced Demand from CACC

Advances in vehicle technology have influenced the development of automated vehicle systems, where vehicles that do not require human intervention are already deployed in the roadway networks. While these advances are proved to increase roadway safety and highway capacity, more research is needed to understand the long-term and regional-level impacts on mobility, land use, energy consumption, and emissions. This study proposes a multi-model approach to analyze the effect of vehicle automation and deep decarbonization policies over a period from 2020 to 2040 in Austin, Texas. We use the Global Change Analysis Model (GCAM) to develop internally the scenarios that are then passed to the SMART Mobility modeling workflow, a large-scale simulation framework combining the POLARIS activity-based travel demand model and mesoscopic traffic simulator with the Autonomie vehicle energy consumption model and the UrbanSim land use simulator. Results suggest that the introduction of vehicles with advanced automation could increase fuel consumption when no decarbonization policies are implemented. Also, advances in vehicle technology research and development could lead to a decline in energy use in the long-term. Energy pricing and vehicle electrification incentives could help reduce the impact of vehicle automation. Finally, our analysis indicates the relevance of introducing land use processes in longterm vehicle automation studies.

land use↗
DOE OSTI2022

The development and use of decision support framework for informing selection of select agent toxins with modelling studies to inform permissible toxin amounts

Many countries have worked diligently to establish and implement policies and processes to regulate high consequence pathogens and toxins that could have a significant public health impact if misused. In the United States, the Antiterrorism and Effective Death Penalty Act of 1996 (Public Law 104-132, 1996), as amended by the Bioterrorism Preparedness and Response Act of 2002 (Public Law 107-188, 2002) requires that the Department of Health and Human Services (HHS) [through the Centers for Disease Control and Prevention (CDC)] establish a list of bacteria, viruses, and toxins that have the potential to pose a severe threat to public health and safety. Currently, this list is reviewed and updated on a biennial basis using input from subject matter experts (SMEs). We have developed decision support framework (DSF) approaches to facilitate selection of select toxins and, where toxicity data are known, conducted modelling studies to inform selection of toxin amounts that should be excluded from select agent regulations. Exclusion limits allow laboratories to possess toxins under an established limit to support their research or teaching activities without the requirement to register with the Federal Select Agent Program. Fact sheets capturing data from a previously vetted SME workshop convened by CDC, literature review and SME input were developed to assist in evaluating toxins using the DSF approach. The output of the DSF analysis agrees with the current select toxin designations, and no other toxins evaluated in this study were recommended for inclusion on the select agent and toxin list. To inform the selection of exclusion limits, attack scenarios were developed to estimate the amount of toxin needed to impact public health. Scenarios consisted of simulated aerosol releases of a toxin in high-population-density public facilities and the introduction of a toxin into a daily consumable product supply chain. Using published inhalation and ingestion median toxic dose (TD 50 ) and median lethal dose (LD 50 ) values, where available, a range of toxin amounts was examined to estimate the number of people exposed to these amounts in these scenarios. Based on data generated by these models, we proposed toxin exclusion values corresponding to levels below those that would trigger a significant public health response (i.e., amounts estimated to expose up to ten people by inhalation or one hundred people by ingestion to LD 50 or TD 50 levels of toxin in the modeled scenarios).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian

Complex interactions exist between microbiomes and their hosts. Increasingly, defensive metabolites that have been attributed to host biosynthetic capability are now being recognized as products of host-associated microbes. These unique metabolites often have bioactivity targets in human disease and can be purposed as pharmaceuticals. Polyketides are a complex family of natural products that often serve as defensive metabolites for competitive or pro-survival purposes for the producing organism, while demonstrating bioactivity in human diseases as cholesterol lowering agents, anti-infectives, and anti-tumor agents. Marine invertebrates and microbes are a rich source of polyketides. Palmerolide A, a polyketide isolated from the Antarctic ascidian Synoicum adareanum, is a vacuolar-ATPase inhibitor with potent bioactivity against melanoma cell lines. The biosynthetic gene clusters (BGCs) responsible for production of secondary metabolites are encoded in the genomes of the producers as discrete genomic elements. A candidate palmerolide BGC was identified from a S. adareanum microbiome-metagenome based on a high degree of congruence with a chemical structure-based retrobiosynthetic prediction. Protein family homology analysis, conserved domain searches, active site and motif identification were used to identify and propose the function of the ~75 kbp trans-acyltransferase (AT) polyketide synthase-non-ribosomal synthase (PKS-NRPS) domains responsible for the stepwise synthesis of palmerolide A. Though PKS systems often act in a predictable co-linear sequence, this BGC includes multiple trans-acting enzymatic domains, a non-canonical condensation termination domain, a bacterial luciferase-like monooxygenase (LLM), and is found in multiple copies within the metagenome-assembled genome (MAG). Detailed inspection of the five highly similar pal BGC copies suggests the potential for biosynthesis of other members of the palmerolide chemical family. This is the first delineation of a biosynthetic gene cluster from an Antarctic microbial species, recently proposed as Candidatus Synoicihabitans palmerolidicus. These findings have relevance for fundamental knowledge of PKS combinatorial biosynthesis and could enhance drug development efforts of palmerolide A through heterologous gene expression.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Resilient Inverter-Driven Black Start with Collective Parallel Grid-Forming Operation: Preprint

As the modern power systems are experiencing exceptional changes with increasing penetration of inverter-based resources (IBRs), system restoration using IBRs has received attention. Using local grid-forming (GFM) assets near consumers, engineered to establish grid voltages in the absence of a stiff grid, i.e., bottom-up restoration, a distribution system would obtain high system resilience, by not relying on the bulk power system restoration requiring significant human intervention and procedure to restore. This paper studies the technical feasibility of the novel approach with detailed electromagnetic transient (EMT) simulations. To thoroughly evaluate the potential of GFM inverters and technical challenges in IBR-driven black start, a detailed three-phase inverter model is developed, including negative-sequence control for voltage balance and a phase-by-phase current limiter to sustain momentary overloading during the black start. To examine dynamic aspects of the black start process, the EMT simulation also models transformer and motor dynamics to emulate their inrush and start-up behaviors as well as network dynamics. In addition, active involvement of grid-following distributed energy resources (DER) is also studied to facilitate the black start process. It is shown that, by allowing multiple GFM inverters to collectively black start without master-slave coordination, a system can achieve high resilience even with a fraction of assets lost. Two test cases of inverter-driven black start using two and one GFM inverters, respectively, for a heavily unbalanced 2-MVA distribution feeder are demonstrated. Takeaways for further study and field deployment are provided.

grid-forming inverter↗
DOE OSTI2022

A systematic exploration of boceprevir-based main protease inhibitors as SARS-CoV-2 antivirals

Boceprevir is an HCV NSP3 inhibitor that was explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (M Pro ) and contains an α-ketoamide warhead, a P1 β-cyclobutylalanyl moiety, a P2 dimethylcyclopropylproline, a P3 tert-butylglycine, and a P4 N-terminal tert-butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based M Pro inhibitors including PF-07321332 and characterized their M Pro inhibition potency in test tubes (in vitro) and 293T cells (in cellulo). Crystal structures of M Pro bound with 10 inhibitors and cytotoxicity and antiviral potency of 4 inhibitors were characterized as well. Replacing the P1 site with a β-(S-2-oxopyrrolidin-3-yl)-alanyl (Opal) residue and the warhead with an aldehyde leads to high in vitro potency. The original moieties at P2, P3 and the P4 N-terminal cap positions in boceprevir are better than other tested chemical moieties for high in vitro potency. In crystal structures, all inhibitors form a covalent adduct with the M Pro active site cysteine. Here, the P1 Opal residue, P2 dimethylcyclopropylproline and P4 N-terminal tert-butylcarbamide make strong hydrophobic interactions with M Pro , explaining high in vitro potency of inhibitors that contain these moieties. A unique observation was made with an inhibitor that contains a P4 N-terminal isovaleramide. In its M Pro complex structure, the P4 N-terminal isovaleramide is tucked deep in a small pocket of M Pro that originally recognizes a P4 alanine side chain in a substrate. Although all inhibitors show high in vitro potency, they have drastically different in cellulo potency to inhibit ectopically expressed M Pro in human 293T cells. In general, inhibitors with a P4 N-terminal carbamide or amide have low in cellulo potency. This trend is reversed when the P4 N-terminal cap is changed to a carbamate. The installation of a P3 O-tert-butyl-threonine improves in cellulo potency. Three molecules that contain a P4 N-terminal carbamate were advanced to cytotoxicity tests on 293T cells and antiviral potency tests on three SARS-CoV-2 variants. They all have relatively low cytotoxicity and high antiviral potency with EC 50 values around 1 μM. A control compound with a nitrile warhead and a P4 N-terminal amide has undetectable antiviral potency. Based on all observations, we conclude that a P4 N-terminal carbamate in a boceprevir derivative is key for high antiviral potency against SARS-CoV-2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Mercury methylation by metabolically versatile and cosmopolitan marine bacteria

Microbes transform aqueous mercury (Hg) into methylmercury (MeHg), a potent neurotoxin that accumulates in terrestrial and marine food webs, with potential impacts on human health. This process requires the gene pair hgcAB, which encodes for proteins that actuate Hg methylation, and has been well described for anoxic environments. However, recent studies report potential MeHg formation in suboxic seawater, although the microorganisms involved remain poorly understood. In this study, we conducted large-scale multi-omic analyses to search for putative microbial Hg methylators along defined redox gradients in Saanich Inlet, British Columbia, a model natural ecosystem with previously measured Hg and MeHg concentration profiles. Analysis of gene expression profiles along the redoxcline identified several putative Hg methylating microbial groups, including Calditrichaeota, SAR324 and Marinimicrobia, with the last the most active based on hgc transcription levels. Marinimicrobia hgc genes were identified from multiple publicly available marine metagenomes, consistent with a potential key role in marine Hg methylation. Computational homology modelling predicts that Marinimicrobia HgcAB proteins contain the highly conserved amino acid sites and folding structures required for functional Hg methylation. Furthermore, a number of terminal oxidases from aerobic respiratory chains were associated with several putative novel Hg methylators. Our findings thus reveal potential novel marine Hg-methylating microorganisms with a greater oxygen tolerance and broader habitat range than previously recognized.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Improving Self-Driving Labs: Quantifying System-Level Experiment Repeatability and Broadening Instrument-Level Compatibility

Modular Autonomous Research System (MARS) is a self-driving laboratory (SDL) which performs wet-lab science with peptide-lanthanide combinations in an automated and, ultimately, an autonomous manner to aid in soil analysis for domestic lithium mining. Autonomous experimentation involves automated experimentation, experiment planning, and active learning. MARS consists of a 6-axis robotic arm (UR5e) on a linear rail, pipette robots (Opentrons 2), and microplate readers. These components transport, operate on, and collect data with chemical solutions in standard labware. For effective autonomy, MARS must perform system-level labware operations repeatably, plan experiments autonomously, and be portable between research-domains. Repeatability is evaluated by labware placement precision, such that future operations can properly locate labware, as well as the elapsed time, so that low variance mean estimates of experiment duration can inform high-level researcher decision making. Autonomous experiment planning is the next step to decouple experimentation from human management; however, there is a conflict between the ideal system-level experiment goals and the constraints imposed by instruments’ limitations. Sub-domain portability is a long-term goal to extend MARS’ research beyond the chemistry of peptide-lanthanide binding to other sub-domains without having to invest significant overhead to system retrofitting. To address these goals, we manually trained the robotic arm labware placement and modelled statistical failurerate and uncertainty Additionally, we benchmarked the duration and variance of each experiment sub-operation as a heuristic for research decision making. Next, we use a parameterized geometric program (PGP) approach to design experiments that optimize system-level objectives and satisfy instrument-level constraints. Lastly, we proposed a Python framework to maximize MARS’ extensibility to other scientific sub-domains through a JSON-based experiment specification.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Electrocatalytic nitrate reduction: controlling adsorbate affinity to tailor reaction products

Every year, Haber-Bosch nitrogen fixation to form ammonia releases immense volumes of CO2. At the same time, nitrate contamination from untreated wastewater threatens human health across the US. Development of circular processes to efficiently upgrade waste nitrate for reuse is critical to sustainably address this growing environmental hazard. Electrochemical reduction of nitrate operates at ambient temperatures and pressures, and can leverage distributed renewable energy sources and water as a hydrogen source for ammonia production. However, current catalysts lack electron efficiency in reducing nitrate versus water, lack selectivity in forming ammonia as a product, or rely on expensive rare metals, making widespread implementation unfeasible. To overcome these limitations, this proposal seeks a mechanistic understanding of nitrate electrochemical reduction on earth abundant metals and their alloys, with the goal of identifying active-site properties that improve both Faradaic efficiency and product selectivity. This insight will extend to other electrocatalytic reductive process that compete with water reduction.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2025

STILGAR End-of-Project Report

The Subsurface Tunnel Imaging LeveraGed by Analysis of Rayleigh wave ellipticity (STILGAR) project demonstrated an integrated geophysical approach for detecting, locating, and characterizing underground structural changes using dense seismic arrays and advanced inversion techniques. Field campaigns were conducted at two operational mines—the Redmond salt mine (Utah) and Graymont Pleasant Gap limestone mine (Pennsylvania)—providing real-world testbeds for monitoring anthropogenic subsurface activity. At the Redmond salt mine, seismic interferometry combined with back-projection inversion successfully identified continuous, low-amplitude signals from mining operations. The approach differentiated stationary from migrating anthropogenic sources, captured daily operational cycles, and validated the potential of passive seismic monitoring for remote detection of underground activity. At the Graymont Pleasant Gap mine, two dense seismic deployments in the spring and fall of 2023 generated over 4 TB of high-resolution data. Key outcomes included the relocation of 199 underground and 8 surface explosions with accuracies within tens of meters and the development of a 3D P-wave velocity model using the triple-difference tomography algorithm (tomoTD) that resolved major structural features such as the mine entrance, low-velocity tunnels, and roof-collapse areas. Ambient noise cross-correlation and back-projection analyses revealed persistent sources linked to ongoing mining activity, whereas horizontal-to-vertical spectral ratio (HVSR) and ellipticity studies confirmed stable site responses across seasons and identified soil thickness trends consistent with regional erosional and depositional processes. Checkerboard and sensitivity tests further validated the robustness of the tomographic results. Overall, the findings emphasize that although significant progress has been made in subsurface imaging, further work is needed to enhance the detection and localization of underground structures. Accurate imaging requires higher frequencies, yet anthropogenic sources tend to dominate the seismic record at those frequencies, and high-frequency surface waves are affected by higher modes that complicate interpretation. The improved detection and localization of human-induced signals enabled detailed temporal and spatial mapping of daily mine operations, demonstrating the feasibility of continuous anthropogenic source monitoring. Sensitivity to signals from nontraditional sources, such as fan operations, highlights the broader applicability of this approach to other industrial environments in which continuous and impulsive signals are present. The field campaigns produced a substantial volume of high-quality seismic data, supporting the development and testing of new methods for seismic source characterization and subsurface imaging. Future deployments should include sensors capable of recording lower frequencies to probe deeper structures, increase bandwidth to enhance resolution and sensitivity to both shallow and deep targets, and collect additional large-scale datasets to refine imaging and source characterization techniques. Moreover, conducting 3D modeling studies of seismic wavefields at higher frequencies will provide a better understanding of wave scattering and cavity–wavefield interactions in complex underground environments. In conclusion, the STILGAR project demonstrated that integrated seismic monitoring can effectively characterize underground operations, capturing both natural and anthropogenic signals. The approaches developed provide a foundation for improved detection, localization, and imaging of subsurface structures and are directly transferable to broader industrial monitoring applications.

58 GEOSCIENCES↗
DOE OSTI2021

Additive manufacturing and applications of nanomaterial-based sensors

Nanoscale materials possess distinct physical and chemical attributes including size-dependent properties, quantum confinement, high surface-to-volume ratio, and superior catalytic activity. These unique qualities enable sensors with high sensitivity, robustness, and fast time response. As the emergence of the Internet of Things (IoT) demands increased production of sensors, it also provides an impetus for concentrated nanomaterial-based sensor research. Meanwhile, additive manufacturing (AM) of nanomaterial-based sensors is critical to bridge the gap between one-off, lab-scale fabrication and cost-effective, industrial-scale production with high reproducibility. By applying the design flexibility and cost savings of AM techniques, a new generation of nanomaterial-based sensing platforms can be integrated with IoT devices in the consumer space. Furthermore, emergent research in human-machine interfaces, food safety, and point-of-care diagnostics will be expedited by the development of sensors that can be printed with irregular form factors. In this Review, the relative strengths and weaknesses of printed sensor systems based on zero-, one-, and two-dimensional nanomaterials are discussed. In addition, sensors enabled by printable soft nanomaterials, heterostructures, and nanocomposites are surveyed due to their synergistic advantages for wearable healthcare monitoring and soft robotics. Lastly, a roadmap for the next decade of research on this topic is provided.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBD surf ) in mice compared to RBD-encapsulated polymersomes (RBD encap ) and unformulated RBD (RBD free ), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD surf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD surf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBD surf and RBD encap drove similarly robust CD4 + and CD8 + T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

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

Temporal dynamics of the multi-omic response to endurance exercise training

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Probing the structure and function of the protease domain of botulinum neurotoxins using single-domain antibodies

Botulinum neurotoxins (BoNTs) are among the deadliest of bacterial toxins. BoNT serotype A and B in particular pose the most serious threat to humans because of their high potency and persistence. To date, there is no effective treatment for late post-exposure therapy of botulism patients. Here, we aim to develop single-domain variable heavy-chain (VHH) antibodies targeting the protease domains (also known as the light chain, LC) of BoNT/A and BoNT/B as antidotes for post-intoxication treatments. Using a combination of X-ray crystallography and biochemical assays, we investigated the structures and inhibition mechanisms of a dozen unique VHHs that recognize four and three non-overlapping epitopes on the LC of BoNT/A and BoNT/B, respectively. We show that the VHHs that inhibit the LC activity occupy the extended substrate-recognition exosites or the cleavage pocket of LC/A or LC/B and thus block substrate binding. Notably, we identified several VHHs that recognize highly conserved epitopes across BoNT/A or BoNT/B subtypes, suggesting that these VHHs exhibit broad subtype efficacy. Further, we identify two novel conformations of the full-length LC/A, that could aid future development of inhibitors against BoNT/A. Our studies lay the foundation for structure-based engineering of protein- or peptide-based BoNT inhibitors with enhanced potencies and cross-subtypes properties.

59 BASIC BIOLOGICAL SCIENCES↗