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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 109 records · Page 6

Lab Home Testing of Residential Isolation Space Control to Minimize Infectious Disease Transmission in Existing Single-Family Homes

Existing evidence strongly suggests that viral infectious diseases can be transmitted via an airborne route across distances in indoor environments. Accordingly, the risk of airborne transmission within homes should be managed. The public health emergency associated with SARS-CoV-2 makes controlling airborne transmission of respired viruses in indoor environments critical, especially in poorly ventilated indoor environments. The effectiveness of engineering interventions requiring minor efforts that create a negative-pressure isolation zone (IZ) for a contagious person has yet to be tested for existing residential homes. To mitigate the risk of airborne virus transmission and maximize health protection for the population in existing single-family homes, the relative effectiveness of several control strategies are investigated in this report. While very high-efficiency MERV filtration, high ventilation rates, and other controls can help be effective, most occupants are not likely to have the time or means for advanced measures found in hospitals. This project focused on testing relatively simple efforts that utilize existing or easy to acquire materials and simple processes.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Network analysis uncovers the communication structure of SARS-CoV-2 spike protein identifying sites for immunogen design

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand the structure and dynamics of this complex pathogen. The spike glycoprotein of SARS-CoV-2 is a significant target for immunogens as it is the means by which the virus enters human cells, while simultaneously sporting mutations responsible for immune escape. These functional and escape processes are regulated by complex molecular-level interactions. Our study presents quantitative insights on domain and residue contributions to allosteric communication, immune evasion, and local- and global-level control of functions through the derivation of a weighted graph representation from all-atom MD simulations. Focusing on the ancestral form and the D614G-variant, we provide evidence of the utility of our approach by guiding the selection of a mutation that alters the spike’s stability. Taken together, the network approach serves as a valuable tool to evaluate communication “hot-spots” in proteins to guide design of stable immunogens.

60 APPLIED LIFE SCIENCES↗

SIS-AOP Cueing/Segmenting Algorithm (FOA_SIS-AOP) Using the Sandia FOA 4.0 Framework

For machine vision, one of the most important operations is fast and effective object cueing or segmentation. Sandia National Labs has a long history of development and implementation of very fast and effective cueing/segmentation algorithms. This report covers the history, motivation and implementation of evolving frameworks (Sandia FOA Frameworks) upon which this long legacy of successful algorithms are built. The report describes the innovative microprocessor implementation, enabling extremely fast morphological processing, combined with a novel adaptive quantization front - end and a feature - based backend that resulted in Sandia developing fast and effective cueing in a wide variety of applications, from defect detection to SAR ATR. The report covers evolution from Sandia FOA 1.0 Framework (1995) to current Sandia FOA 4.0 Framework (2021). Requirements for the cueing algorithm for SIS - AOP (FOA_SIS - AOP) that drove the Sandia FOA 4.0 Framework development are discussed, along with information on how to use the Sandia FOA Frameworks.

97 MATHEMATICS AND COMPUTING↗

A Radiation-Hard 8-Channel 15-Bit 40-MSPS ADC for the ATLAS Liquid Argon Calorimeter Readout

The custom design of a radiation-hardened, 8-channel, 40-MSPS, 15-bit resolution, 14.2-bit dynamic range, 11.4-ENOB ADC data acquisition ASIC fabricated in a commercial 65-nm triple-well CMOS technology is presented. The ADC is developed for and integrates seamlessly into the readout system for the ATLAS liquid argon (LAr) calorimeter in the high-luminosity large hadron collider (HLLHC) upgrade at CERN, which will require a total of 364 936 ADC channels. A three-stage MDAC+SAR pipelined ADC architecture was designed to meet the physics requirements and scientific goals of the ATLAS experiment. The ADC is a fully self-contained data acquisition system that includes foreground calibration, digital data processing, digital control, and supporting circuitry. The measured performance shows the ADC achieves a competitive dynamic range and SNDR, and it meets or exceeds the ATLAS analog requirements. Radiation tolerance and scalability design considerations were implemented at the device-, circuit-, and system-level. Radiation-hardening-by-design techniques used include redundancy for digital circuits, the use of MiM capacitors, and a hybrid RC-DAC for the ADC core. The ADC ASIC was demonstrated to be robust against the effects of the intense radiation expected in the HL-LHC experimental environment.

DAQ↗

Impacts of Vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 Variants Alpha and Delta on Coronavirus Disease 2019 Transmission Dynamics in Four Metropolitan Areas of the United States

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. In conclusion, estimated takeoff times are consistent with genomic surveillance data.

60 APPLIED LIFE SCIENCES↗

Air Evacuation Bridge

Researchers at Los Alamos National Laboratory are researching and designing technology intended to help reduce the exposure of patients and medical staff to pathogens, such as SARS-CoV-2 while providing medical staff the dexterity and flexible work conditions necessary to conduct routine and complex patient care on infected patients. This investigative technology would potentially enable hospitals to adapt, utilize, and re-purpose existing and otherwise infrequently used equipment in the fight against COVID-19, thereby saving hospitals significant money, reducing exposure to staff and patients, and increasing the supply of critically needed devices at a time when supplies are scarce in the market place. A provisional patent has been filed on the technology and we are seeking a commercialization partner to license and further develop the product for commercial purposes, including processing the device through the FDA authorization or clearance process. Once FDA has cleared the product, at least one hospital system has expressed interest in the experimental test components for use in their hospitals.

42 ENGINEERING↗

Apodized RFI Filtering of Synthetic Aperture Radar Images

Fine resolution Synthetic Aperture Radar (SAR) systems necessarily require wide bandwidths that often overlap spectrum utilized by other wireless services. These other emitters pose a source of Radio Frequency Interference (RFI) to the SAR echo signals that degrades SAR image quality. Filtering, or excising, the offending spectral contaminants will mitigate the interference, but at a cost of often degrading the SAR image in other ways, notably by raising offensive sidelobe levels. This report proposes borrowing an idea from nonlinear sidelobe apodization techniques to suppress interference without the attendant increase in sidelobe levels. The simple post-processing technique is termed Apodized RFI Filtering (ARF).

42 ENGINEERING↗

Electronic Interactions Between the Receptor-Binding Domain of Omicron Variants and Angiotensin-Converting Enzyme 2: A Novel Amino Acid–Amino Acid Bond Pair Concept

SARS-CoV-2 remains a severe threat to worldwide public health, particularly as the virus continues to evolve and diversify into variants of concern (VOCs). Among these VOCs, Omicron variants exhibit unique phenotypic traits, such as immune evasion, transmissibility, and severity, due to numerous spike protein mutations and the rapid subvariant evolution. These Omicron subvariants have more than 15 mutations in the receptor-binding domain (RBD), a region of the SARS-CoV-2 spike protein that is important for recognition and binding with the angiotensin-converting enzyme 2 (ACE2) human receptor. To address the impact of these high numbers of Omicron mutations on the binding process, we have developed a novel method to precisely quantify amino acid interactions via the amino acid–amino acid bond pair (AABP). We applied this concept to investigate the interface interactions of the RBD–ACE2 complex in four Omicron Variants (BA.1, BA.2, BA.5, and XBB.1.16) with its Wild Type counterpart. Based on the AABP analysis, we have identified all the sites that are affected by mutation and have provided evidence that unmutated sites are also impacted by mutation. We have calculated that the binding between RBD and ACE2 is strongest in OV BA.1, followed by OV BA.2, WT, OV BA.5, and OV XBB.1.16. We also present the partial charge values for all 311 residues across these five models. Our analysis provides a detailed understanding of changes caused by mutation in each Omicron interface complex.

Biochemistry & Molecular Biology↗

A comprehensive collection of systems biology data characterizing the host response to viral infection

The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As a result, by comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

59 BASIC BIOLOGICAL SCIENCES↗

Fabrication Lessons Learned of Transportation Packaging from the Perspective of a Design Authority - 20322

This paper presents lessons learned regarding fabricating packaging systems from the perspective of a design authority (DA). Capturing and implementing lessons learned is critical for an organization to reduce systematic project risk and thereby promote the likelihood of project success. This paper defines the design authority as the organization responsible for technical design, resolving technical design issues, quality assurance program, and maintenance of the packaging system license. A package system is defined as the packaging, its contents, and auxiliary equipment. Packages are certified by the NRC under 10 CFR 71[1] for transportation by ground. The following lessons learned subjects are presented in the paper: quality assurance, interpretation of drawing dimensional requirements, execution of manufacturing processes, hardware dimensional inspection, and leakage rate testing. All discrepancies presented in this paper have been resolved as described in the appropriate final data package. All described package systems are in compliance with their Safety Analysis Report (SAR) and certificate of conformance requirements. The intent of this paper is to identify opportunities for improving the outcome of future projects and to mitigate fabrication challenges proactively. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Cleavage at the nsp5–nsp6 site of SARS-CoV-2 main protease intermediate precursor is faster from a monomer than a dimer form

Our previous studies of severe acute respiratory syndrome coronavirus 2 main protease (MPro) precursor monomer indicate that the initial N-terminal nonstructural protein (nsp)4/nsp5 cleavage occurs intramolecularly, with a small fraction of the active site loop equilibrium being in the active state. To understand the influence of dimer formation of MPro upon N-terminal cleavage on the subsequent C-terminal nsp5/nsp6 intermolecular cleavage kinetics, the stepwise processing of a monomeric, inactive precursor containing the native terminal cleavage sites of MPro (MBP- (−6) MPro C145A(+3) -GB1-6H, 86.2 kDa) by mature WT MPro (MPro WT ) was investigated. Differential scanning fluorimetry and analytical ultracentrifugation measurements of various MPro constructs suggest that the C145A mutation decreases the dimer dissociation constant (K dimer ) by ∼26-fold, relative to WT C145 and H41A. The monomeric precursor’s nsp4–nsp5 site appears to saturate MProWT’s active sites and cleave faster, followed by a slower first-order cleavage at the C-terminal site. No detectable product resulting from the C-terminal cleavage is observed until most of the N-terminal cleavage is complete. The initial intermediate product (termed MPro C145A-IP ) is a homodimer with an estimated K dimer of <0.05 μM. In contrast, the first-order kinetics observed for the cleavage of the monomeric form of the intermediate product is at least 300 times faster than that of the dimer form. Room-temperature X-ray structure of the MPro C145A-IP –ensitrelvir complex is like that of the MPro WT –ensitrelvir complex and reveals a dynamic C-terminal region including MPro residues 302 to 306. These results are interpreted from the point of view of a mechanism in which nsp5–nsp6 cleavage may occur from a monomeric intermediate, and dimer formation restricts this cleavage.

60 APPLIED LIFE SCIENCES↗

Characterization of alternate encounter assemblies of SARS-CoV-2 main protease

The assembly of two monomeric constructs spanning segments 1-199 (MPro 1-199 ) and 10-306 (MPro 10-306 ) of SARS-CoV-2 main protease (MPro) was examined to assess the existence of a transient heterodimer intermediate in the N-terminal autoprocessing pathway of MPro model precursor. Together, they form a heterodimer population accompanied by a 13-fold increase in catalytic activity. Addition of inhibitor GC373 to the proteins increases the activity further by ~7-fold with a 1:1 complex and higher order assemblies approaching 1:2 and 2:2 molecules of MPro 1-199 and MPro 10-306 detectable by analytical ultracentrifugation and native mass estimation by light scattering. Assemblies larger than a heterodimer (1:1) are discussed in terms of alternate pathways of domain III association, either through switching the location of helix 201 to 214 onto a second helical domain of MPro 10-306 and vice versa or direct interdomain III contacts like that of the native dimer, based on known structures and AlphaFold 3 prediction, respectively. At a constant concentration of MPro 1-199 with molar excess of GC373, the rate of substrate hydrolysis displays first order dependency on the MPro 10-306 concentration and vice versa. An equimolar composition of the two proteins with excess GC373 exhibits half-maximal activity at ~6 μM MPro 1-199 . Catalytic activity arises primarily from MPro 1-199 and is dependent on the interface interactions involving the N-finger residues 1 to 9 of MPro 1-199 and E290 of MPro 10-306 . Importantly, our results confirm that a single N-finger region with its associated intersubunit contacts is sufficient to form a heterodimeric MPro intermediate with enhanced catalytic activity.

60 APPLIED LIFE SCIENCES↗

Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling

Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% of all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach for modulating RAS activity is to target and affect the activity of proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). In this paper, we report on structure–activity relationships (SAR) in an indole series of compounds. Using structure-based design, we systematically explored substitution patterns on the indole nucleus, the pendant amino acid moiety, and the linker unit that connects these two fragments. Best-in-class compounds activate the nucleotide exchange process at submicromolar concentrations in vitro, increase levels of active RAS–GTP in HeLa cells, and elicit signaling changes in the mitogen-activated protein kinase–extracellular regulated kinase (MAPK–ERK) pathway, resulting in a decrease in pERK1/2 T202/Y204 protein levels at higher compound concentrations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Synthetic aperture integration (SAI) algorithm for SAR imaging

A method and system for detecting the presence of subsurface objects within a medium is provided. In some embodiments, the imaging and detection system operates in a multistatic mode to collect radar return signals generated by an array of transceiver antenna pairs that is positioned across the surface and that travels down the surface. The imaging and detection system pre-processes the return signal to suppress certain undesirable effects. The imaging and detection system then generates synthetic aperture radar images from real aperture radar images generated from the pre-processed return signal. The imaging and detection system then post-processes the synthetic aperture radar images to improve detection of subsurface objects. The imaging and detection system identifies peaks in the energy levels of the post-processed image frame, which indicates the presence of a subsurface object.

97 MATHEMATICS AND COMPUTING↗

A funnel approach to enable analyses of epitope-specific human CD4 T cells specific for influenza and SARS-CoV-2

Protection against pathogens relies heavily on the adaptive immune response, whose key regulators are CD4 T cells. CD4 T cells, notable for their complex repertoire and functional potential, can most easily be dissected by identifying, quantifying, characterizing, and isolating epitope-specific cells. In the study reported here, we present a systematic and unbiased strategy that has enabled the identification of highly immunogenic peptide epitopes derived from influenza virus and SARS-CoV-2, presented by human HLA-DR proteins. Coupling the use of HLA-DR transgenic mice with infection and vaccination and highly sensitive epitope-specific cytokine ELISpot assays, we have narrowed the potential epitopes from 450 to 600 peptides to 5–15 peptides for each allele by an iterative process of elimination and selection, which we have termed a funnel approach. These epitopes have been validated in HLA-DR-typed human CD4 T cells directly ex vivo and enabled the derivation and implementation of HLA-DR peptide tetramers. Tetramer staining of human PBMCs enriched for CD4 T memory populations from healthy adult subjects, highlighted this approach as a sensitive and specific method for identifying novel epitopes, and subsequent CD4 T-cell responses to human viral infections.

CD4 T cell↗

Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies)

We describe a general method that allows structure determination of small proteins by single-particle cryo-electron microscopy (cryo-EM). The method is based on the availability of a target-binding nanobody, which is then rigidly attached to two scaffolds: 1) a Fab fragment of an antibody directed against the nanobody and 2) a nanobody-binding protein A fragment fused to maltose binding protein and Fab-binding domains. The overall ensemble of ~120 kDa, called Legobody, does not perturb the nanobody–target interaction, is easily recognizable in EM images due to its unique shape, and facilitates particle alignment in cryo-EM image processing. The utility of the method is demonstrated for the KDEL receptor, a 23-kDa membrane protein, resulting in a map at 3.2-Å overall resolution with density sufficient for de novo model building, and for the 22-kDa receptor-binding domain (RBD) of SARS-CoV-2 spike protein, resulting in a map at 3.6-Å resolution that allows analysis of the binding interface to the nanobody. The Legobody approach thus overcomes the current size limitations of cryo-EM analysis.

59 BASIC BIOLOGICAL SCIENCES↗

Envisat Track 349 and Sentinel-1A Track 64 Interferometric Synthetic Aperture Radar Data of Coso Geothermal Field, California, USA, 2004-2016

This submission contains tarred pair directories for interferometric synthetic aperture radar (InSAR) data covering Coso Geothermal Field in California, USA. Explanation of pair subdirectories: Pairs are formed using the InSAR processing software GMT5SAR (Sandwell et al., 2011). Pair subdirectories are named by starting and ending epochs in YYYYMMDD_YYYYMMDD format. Each tarred pair directory contains GRD files for phase data (radians), unwrapped range change (drhomaskd, in m), and unwrapped range change rate (drange, in m/yr). The data are given in both latitude/longitude and Universal Transverse Mercator (Zone 11N). Raw Synthetic Aperture Radar (SAR) data from the Envisat satellite mission operated by the European Space Agency (ESA) are copyrighted by ESA and were provided through the WInSAR consortium at the UNAVCO facility. Raw Synthetic Aperture Radar (SAR) data from the Sentinel-1A satellite mission operated by ESA were available free of charge through the Distributed Active Archive Center (DAAC) at the Alaska Satellite Facility (ASF) and through the Sentinels Scientific Data Hub. References: Farr, T.G.; Rosen, P.A.; Caro, E.; Crippen, R.; Duren, R.; Hensley, S.; Kobrick, M.; Paller, M.; Rodriguez, E.; Roth, L.; Seal, D.; Shaffer, S.; Shimada, J.; Umland, J.; Werner, M.; Oskin, M.; Burbank, D.; Alsdorf, D. The Shuttle Radar Topography Mission. Reviews of Geophysics 2007, 45, RG2004. doi:10.1029/2005RG000183. Sandwell, D.; Mellors, R.; Tong, X.; Wei, M.; Wessel, P. Open radar interferometry software for mapping surface deformation. Eos, Transactions American Geophysical Union 2011, 92, 234?234. http://dx.doi.org/10.1029/2011EO280002. doi:10.1029/2011EO280002.

15 GEOTHERMAL ENERGY↗

Standardized report template for indeterminate renal masses at CT and MRI: a collaborative product of the SAR Disease-Focused Panel on Renal Cell Carcinoma

Purpose: To create a succinct yet comprehensive evidence-based structured report template for indeterminate renal masses characterized at CT and MRI. Methods: This IRB-exempt, iterative, multi-institutional quality improvement project was informed by published data derived from a multi-institutional survey and a multi-institutional review of CT and MRI radiology reports. A two-stage blinded Delphi process by the 16-member 12-institution Society of Abdominal Radiology Disease-Focused Panel on Renal Cell Carcinoma was conducted to create a structured report template for indeterminate renal masses evaluated at CT and MRI. Individual reporting characteristics were scored by members as ‘core,’ ‘optional,’ or ‘exclude.’ Threshold for inclusion was ≥ 80% support. If < 80% members considered a characteristic a ‘core’ feature, but ≥ 80% considered it either ‘core’ or ‘optional,’ it was considered an ‘optional’ feature. If neither was the case, the characteristic was excluded. Free-text comments were permitted. Characteristics considered ‘core’ by 50–99% of respondents in Round 1 (i.e., nonunanimous support) and uninvestigated free-text comments were assessed in Round 2. Core and optional structured reporting templates were derived. Results: The response rate was 100% in Round 1 (16/16) and Round 2 (16/16). In Round 1, 5 characteristics had unanimous support as ‘core’ features. Following Round 2, 13 characteristics had ≥ 80% support as ‘core’ features, and 10 characteristics had ≥ 80% support as ‘optional’ features. Structured report templates were derived. Discussion: Structured ‘core’ and ‘optional’ templates for indeterminate renal masses at CT and MRI were derived, which may improve compliance with reporting preferred and essential imaging characteristics.

62 RADIOLOGY AND NUCLEAR MEDICINE↗