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DOE OSTI2024

Human Liver Epithelial Cells (HuH7) Response to HCoV-229E Infection Epigenomics (ATAC-Seq) (ACS-DP4)

The purpose of this experiment was to evaluate how wild-type Human coronavirus strain 229E (HCoV-299E) infection alters chromatin accessibility in infected cells. Sample data was obtained from mock-infected cells, UV-inactivated virus treated cells, and replication competent HCoV-229E infected immortalized human liver cells (HuH7) at 24 hours post infection. Samples were processed using ATAC-seq methods for reported bar coded libraries. Sample data was acquired using an Illumina Hi-Seq 2500 sequencer system and further processed for ATAC-Seq expression analysis.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2015

Meta gene set enrichment analyses link miR-137-regulated pathways with schizophrenia risk

Background: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevant biological pathways, including those involved in nervous system development and function. Methods: In this study, we evaluated the schizophrenia risk of miR-137 target genes within these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets was performed using the stage 1 (21,856 subjects) schizophrenia genome wide association study data from the Psychiatric Genomics Consortium and a small independent replication cohort (244 subjects) from the Mind Clinical Imaging Consortium and Northwestern University. Results: Gene sets of potential miR-137 targets were enriched with variants associated with schizophrenia risk, including target sets involved in axonal guidance signaling, Ephrin receptor signaling, long-term potentiation, PKA signaling, and Sertoli cell junction signaling. The schizophrenia-risk association of SNPs in PKA signaling targets was replicated in the second independent cohort. Conclusions: These results suggest that these biological pathways may be involved in the mechanisms by which this MIR137 variant enhances schizophrenia risk. SNPs in targets and the miRNA host gene may collectively lead to dysregulation of target expression and aberrant functioning of such implicated pathways. Pathway-guided gene set enrichment analyses should be useful in evaluating the impact of other miRNAs and target genes in different diseases.

Genetics & Heredity↗

DOE OSTI2019

Spatial and temporal variation in river corridor exchange across a 5th-order mountain stream network

Although most field and modeling studies of river corridor exchange have been conducted at scales ranging from tens to hundreds of meters, results of these studies are used to predict their ecological and hydrological influences at the scale of river networks. Further complicating prediction, exchanges are expected to vary with hydrologic forcing and the local geomorphic setting. While we desire predictive power, we lack a complete spatiotemporal relationship relating discharge to the variation in geologic setting and hydrologic forcing that is expected across a river basin. Indeed, the conceptual model of Wondzell (2011) predicts systematic variation in river corridor exchange as a function of (1) variation in baseflow over time at a fixed location, (2) variation in discharge with location in the river network, and (3) local geomorphic setting. To test this conceptual model we conducted more than 60 solute tracer studies including a synoptic campaign in the 5th-order river network of the H. J. Andrews Experimental Forest (Oregon, USA) and replicate-in-time experiments in four watersheds. We interpret the data using a series of metrics describing river corridor exchange and solute transport, testing for consistent direction and magnitude of relationships relating these metrics to discharge and local geomorphic setting. We confirmed systematic decrease in river corridor exchange space through the river networks, from headwaters to the larger main stem. However, we did not find systematic variation with changes in discharge through time or with local geomorphic setting. While interpretation of our results is complicated by problems with the analytical methods, the results are sufficiently robust for us to conclude that space-for-time and time-for-space substitutions are not appropriate in our study system. Finally, we suggest two strategies that will improve the interpretability of tracer test results and help the hyporheic community develop robust datasets that will enable comparisons across multiple sites and/or discharge conditions.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS2007

Persistent Seroconversion after Accidental Eye Exposure to Calcifying Nanoparticles

Biosafety of nanomaterials has attracted much attention recently. We report here a case where accidental human eye exposure to biogenic nanosized calcium phosphate in the form of calcifying nanoparticles (CNP) raised a strong IgG immune response against proteins carried by CNP. The antibody titer has persisted over ten years at the high level. The IgG was detected by ELISA using CNPs propagated in media containing bovine and human serum as antigen. The exposure incident occurred to a woman scientist (WS) at a research laboratory in Finland at 1993. CNP, also termed "nanobacteria", is a unique self-replicating agent that has not been fully characterized and no data on biohazards were available at that time. Before the accident, her serum samples were negative for both CNP antigen and anti-CNP antibody using specific ELISA tests (Nanobac Oy, Kuopio, Finland). The accident occurred while WS was harvesting CNP cultures. Due to a high pressure in pipetting, CNP pellet splashed into her right eye. Both eyes were immediately washed with water and saline. The following days there was irritation and redness in the right eye. These symptoms disappeared within two weeks without any treatment. Three months after the accident, blood and urine samples of WS were tested for CNP cultures (2), CNP-specific ELISA tests, and blood cell counts. Blood cell counts were normal, CNP antigen and culture tests were negative. A high IgG anti-CNP antibody titer was detected (see Figure). The antibodies of this person have been used thereafter as positive control and standard in ELISA manufacturing (Nano-Sero IgG ELISA, Nanobac Oy, Kuopio, Finland).

Ciftcioglu, Neva↗

NASA NTRS2021

Northern Great Plains Disasters: Using Earth Observations to Enhance Flood Monitoring on Tribal Lands in the Northern Great Plains

In 2019, the Great Plains experienced unprecedented catastrophic flooding. Large flood events are predicted to increase in frequency and severity, posing risks to communities in this region, particularly Tribal Nations. We used data from Sentinel-1 C-band Synthetic Aperture Radar (C-SAR), imagery from the Sentinel-2 MultiSpectral Instrument (MSI), and digital elevation models (DEMs) from the Shuttle Radar Topography Mission (SRTM) within Google Earth Engine to map historical floods in the region beginning in 2014 with particular attention to the Rosebud Sioux Reservation and the tribal lands of other Great Plains Tribal Water Alliance members. This historical mapping used C-SAR for a combined method approach with a Z-score algorithm in addition to an index for flooded short vegetation. We also developed a flood risk map by weighting different flood predictor variables according to flood risk literature. These variables included soil drainage from the Soil Survey Geographic Database (SSURGO); elevation, slope, and Topographic Wetness Index (TWI) derived from digital elevation models; precipitation from Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS); land cover from the National Land Cover Database (NLDC); and Normalized Difference Vegetation Index (NDVI) derived from Landsat 8 Operational Land Imager (OLI). From the flood extent and risk maps, we identified widespread flooding in short vegetation (including cropland) and noted flood susceptibility in regions exhibiting high social vulnerability and low community resilience (FEMA indices). We created an ArcGIS Online StoryMap to share project background, results, and data. Additionally, we provided a written tutorial so partners may replicate the flood mapping for future flood events.

Anna Ballasiotes↗

NASA NTRS2022

Maldives Climate: Monitoring Shoreline Changes and Island Loss in Response to Climate Change

Global sea level rise as a result of climate change continues to pose a critical threat to coastal ecosystems and populations. The archipelagic country of the Maldives is of critical concern due to being one of the lowest lying areas in the world. The development of reclaimed land in the Maldives by sand dredging has been a frequent response to both increasing sea levels and population increase. Such disturbance can lead to increased sedimentation off the coast and negatively impact coastal environments. Remote sensing tools such as satellite imagery have proved to be an effective tool in observing coastal changes in response to climate change and development. NASA DEVELOP created a methodology to analyze both water quality and shoreline erosion in the Maldives utilizing satellite imagery. Methods relied on open-source software such as QGIS and Google Earth Engine (GEE) and Satellite Imagery from PlanetScope, Landsat 8 Operational Land Instrument (OLI), Sentinel-2 Multi Spectral Instrument (MSI), and Aqua & Terra Moderate Resolution Imaging Radiospectrometer (MODIS) to analyze the changes in shorelines and assess water quality of select atolls within the Maldives. Findings show less shoreline change in developed parts of the island and more shoreline change in natural parts of the island. Additionally, water quality varies throughout the year and our data did not indicate seasonal trends. The methodology will be replicated to continue to monitor island erosion and water quality with the Maldives and will be applicable to other island and coastal systems.

remote sensing↗

DOE OSTI2015

Methods and apparatus for capture and storage of semantic information with sub-files in a parallel computing system

Techniques are provided for storing files in a parallel computing system using sub-files with semantically meaningful boundaries. A method is provided for storing at least one file generated by a distributed application in a parallel computing system. The file comprises one or more of a complete file and a plurality of sub-files. The method comprises the steps of obtaining a user specification of semantic information related to the file; providing the semantic information as a data structure description to a data formatting library write function; and storing the semantic information related to the file with one or more of the sub-files in one or more storage nodes of the parallel computing system. The semantic information provides a description of data in the file. The sub-files can be replicated based on semantically meaningful boundaries.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2022

Challenges and Lessons Learned from an Analysis of Three Zero Energy Buildings

Zero energy buildings, or zero energy ready buildings, which are designed and operated by public or private commercial property owners can play an important role in reducing carbon emissions. This paper discusses lessons learned and key takeaways from an in-depth analysis of three zero energy buildings that took an integrated design and construction approach to significantly reduce energy use. Two of these projects are new construction and one is a retrofit to zero energy. Findings are based on project literature review, data analysis, and in-depth interviews with the building design teams and staff who were involved during the design, construction, and operation of the buildings. The paper addresses value proposition and cost data in such a way that other building owners can replicate the strategies and technology solutions in response to regulatory mandates or organizational goals. It also provides details on operational improvements taken at each zero energy building to enhance energy performance and increase the potential for load flexibility, and discusses challenges and lessons gleaned from design teams and building staff. The findings serve as a reference for building owners, designers, engineers, contractors, or others interested in, or involved with, the design, construction, or use of new or existing buildings. The paper also includes recommended pathways for widespread adoption of zero energy strategies that can be applied in various locations.

ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION↗

DOE OSTI2023

Modeling of Prismatic High Temperature Reactors in Pronghorn

Pronghorn is a MOOSE based thermal-hydraulics code developed at Idaho National Laboratory (INL) for advanced nuclear reactor analysis. It has been previously applied to model pebble-bed high temperature reactors (HTRs), liquid-metal cooled reactors, and molten salt reactors, among others. This work leverages the coarse-mesh modeling capabilities in Pronghorn to model the Oregon State University (OSU)'s High Temperature Test Facility (HTTF). The HTTF is a 1:4 height scaled-down facility of General Atomics' Modular High Temperature Gas-cooled Reactor (MHTGR). The facility is primarily built to generate data for code and model validation, and does not precisely replicate MHTGR conditions. Nevertheless, it encompasses the main physics associated with MHTGR transients.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE OSTI2016

Actual Waste Demonstration of the Nitric-Glycolic Flowsheet for Sludge Batch 9 Qualification

For each sludge batch that is processed in the Defense Waste Processing Facility (DWPF), the Savannah River National Laboratory (SRNL) performs qualification testing to demonstrate that the sludge batch is processable. Testing performed by the Savannah River National Laboratory has shown glycolic acid to be effective in replacing the function of formic acid in the DWPF chemical process. The nitric-glycolic flowsheet reduces mercury, significantly lowers the catalytic generation of hydrogen and ammonia which could allow purge reduction in the Sludge Receipt and Adjustment Tank (SRAT), stabilizes the pH and chemistry in the SRAT and the Slurry Mix Evaporator (SME), allows for effective rheology adjustment, and is favorable with respect to melter flammability. In order to implement the new flowsheet, SRAT and SME cycles, designated SC-18, were performed using a Sludge Batch (SB) 9 slurry blended from SB8 Tank 40H and Tank 51H samples. The SRAT cycle involved adding nitric and glycolic acids to the sludge, refluxing to steam strip mercury, and dewatering to a targeted solids concentration. Data collected during the SRAT cycle included offgas analyses, process temperatures, heat transfer, and pH measurements. The SME cycle demonstrated the addition of glass frit and the replication of six canister decontamination additions. The demonstration concluded with dewatering to a targeted solids concentration. Data collected during the SME cycle included offgas analyses, process temperatures, heat transfer, and pH measurements. Slurry and condensate samples were collected for subsequent analysis

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

NASA NTRS2010

Analysis of Wind Tunnel Polar Replicates Using the Modern Design of Experiments

The role of variance in a Modern Design of Experiments analysis of wind tunnel data is reviewed, with distinctions made between explained and unexplained variance. The partitioning of unexplained variance into systematic and random components is illustrated, with examples of the elusive systematic component provided for various types of real-world tests. The importance of detecting and defending against systematic unexplained variance in wind tunnel testing is discussed, and the random and systematic components of unexplained variance are examined for a representative wind tunnel data set acquired in a test in which a missile is used as a test article. The adverse impact of correlated (non-independent) experimental errors is described, and recommendations are offered for replication strategies that facilitate the quantification of random and systematic unexplained variance.

Deloach, Richard↗

DOE OSTI2019

Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB)

Classical swine fever virus (CSFV) E2 protein, the major virus structural glycoprotein, is an essential component of the viral envelope. E2 is involved in virus absorption, induction of a protective immune response and is critical for virulence in swine. Using the yeast two-hybrid system, we identified protein phosphatase 1 catalytic subunit beta (PPP1CB), which is part of the Protein Phosphatase 1 (PP1) complex, as a specific binding host partner for E2. We further confirmed the occurrence of this interaction in CSFV-infected swine cells by using two independent methodologies: Co-immunoprecipitation and Proximity Ligation Assay. In addition, we demonstrated that pharmacological activation of the PP1 pathway has a negative effect on CSFV replication while inhibition of the PP1 pathway or knockdown of PPP1CB by siRNA had no observed effect. Overall, our data suggests that the CSFV E2 and PPP1CB protein interact in infected cells, and that activation of the PP1 pathway decreases virus replication.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Integration Development and Testing of Rear Transition Monitor for Beam Current Monitoring System

Addressing baseline effects in accelerator environments is crucial for accurate data acquisition and analysis, since baseline effects can obscure signal clarity and impact the reliability of beam current monitoring systems. There are many potential contributors to baseline noise, such as variations in beam dynamics, electromagnetic interference from nearby equipment, or RF interference. Previous applications of noise reduction systems don t sufficiently filter sources of asynchronous noise, so a new algorithm was implemented. A simulation dataset was created to replicate beam conditions and a Red Pitaya FPGA was used to collect data through the streaming application. A Python script was developed to implement noise reduction algorithms and efforts were made to integrate real-time data streaming with the Redis platform and Acnet Front End infrastructure.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

NASA NTRSDate not supplied

Mars Space Suit Materials Testing Using SHERLOC Calibration Target Data: The Max-CF Project

The Mars 2020/“Perseverance” rover carries a suite of space suit materials as part of the SHERLOC* calibration target [1]. The materials are periodically analyzed by SHERLOC as part of a regular calibration routine and are generating a rich data set regarding their degradation in the martian surface environment. The Maximization of Calibration Fabrics (Max-CF) project will effectively turn SHERLOC data into a measure of space suit material service lifetimes by exposing a second set of materials in a Mars chamber, replicating SHERLOC measurements using the analogous ACRONM** instrument at JSC, and then performing materials testing to include tensile testing. These data can be used to inform space suit design and/or materials development, improving crew safety for future Mars missions. This will partially address NASA’s Strategic Knowledge Gap 8 (Mars Surface Technology) which identifies a need to develop technologies to “sustain humans on the surface of Mars [and] enable human mobility and exploration” [2]. This abstract describes the overall Max-CF project and progress on the laboratory-based study to date.

M Fries↗

DOE OSTI2023

Hierarchical Model Reduction Driven by Machine Learning for Parametric Advection-Diffusion-Reaction Problems in the Presence of Noisy Data

Abstract We propose a new approach to generate a reliable reduced model for a parametric elliptic problem, in the presence of noisy data. The reference model reduction procedure is the directional HiPOD method, which combines Hierarchical Model reduction with a standard Proper Orthogonal Decomposition, according to an offline/online paradigm. In this paper we show that directional HiPOD looses in terms of accuracy when problem data are affected by noise. This is due to the interpolation driving the online phase, since it replicates, by definition, the noise trend. To overcome this limit, we replace interpolation with Machine Learning fitting models which better discriminate relevant physical features in the data from irrelevant unstructured noise. The numerical assessment, although preliminary, confirms the potentialities of the new approach.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2023

Efforts to enhance reproducibility in a human performance research project

Background: Ensuring the validity of results from funded programs is a critical concern for agencies that sponsor biological research. In recent years, the open science movement has sought to promote reproducibility by encouraging sharing not only of finished manuscripts but also of data and code supporting their findings. While these innovations have lent support to third-party efforts to replicate calculations underlying key results in the scientific literature, fields of inquiry where privacy considerations or other sensitivities preclude the broad distribution of raw data or analysis may require a more targeted approach to promote the quality of research output. Methods: We describe efforts oriented toward this goal that were implemented in one human performance research program, Measuring Biological Aptitude, organized by the Defense Advanced Research Project Agency's Biological Technologies Office. Our team implemented a four-pronged independent verification and validation (IV&V) strategy including 1) a centralized data storage and exchange platform, 2) quality assurance and quality control (QA/QC) of data collection, 3) test and evaluation of performer models, and 4) an archival software and data repository. Results: Our IV&V plan was carried out with assistance from both the funding agency and participating teams of researchers. QA/QC of data acquisition aided in process improvement and the flagging of experimental errors. Holdout validation set tests provided an independent gauge of model performance. Conclusions: In circumstances that do not support a fully open approach to scientific criticism, standing up independent teams to cross-check and validate the results generated by primary investigators can be an important tool to promote reproducibility of results.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo

Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 catalytic activity in viral replication, we generated recombinant viruses and replicons encoding a catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site. While substitution to alanine (N40A) reduced catalytic activity by ~10-fold, mutations to aspartic acid (N40D) reduced activity by ~100-fold relative to wild-type. Importantly, the N40A mutation rendered Mac1 unstable in vitro and lowered expression levels in bacterial and mammalian cells. When incorporated into SARS-CoV-2 molecular clones, the N40D mutant only modestly affected viral fitness in immortalized cell lines, but reduced viral replication in human airway organoids by 10-fold. In mice, the N40D mutant replicated at >1000-fold lower levels compared to the wild-type virus while inducing a robust interferon response; all animals infected with the mutant virus survived infection. Our data validate the critical role of SARS-CoV-2 NSP3 Mac1 catalytic activity in viral replication and as a promising therapeutic target to develop antivirals.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1998

An Experimental Investigation of Transverse Tension Fatigue Characterization of IM6/3501-6 Composite Materials Using a Three-Point Bend Test

As composites are introduced into more complex structures with out-of-plane loadings, a better understanding is needed of the out-of-plane, matrix-dominated failure mechanisms. This work investigates the transverse tension fatigue characteristics of IM6/3501 composite materials. To test the 90 degree laminae, a three-point bend test was chosen, potentially minimizing handling and gripping issues associated with tension tests. A finite element analysis was performed of a particular specimen configuration to investigate the influence of specimen size on the stress distribution for a three-point bend test. Static testing of 50 specimens of 9 different sized configurations produced a mean transverse tensile strength of 61.3 Mpa (8.0 ksi). The smallest configuration (10.2 mm wide, Span-to-thickness ratio of 3) consistently exhibited transverse tensile failures. A volume scale effect was difficult to discern due to the large scatter of the data. Static testing of 10 different specimens taken from a second panel produced a mean transverse tensile strength of 82.7 Mpa (12.0 ksi). Weibull parameterization of the data was possible, but due to variability in raw material and/or manufacturing, more replicates are needed for greater confidence. Three-point flex fatigue testing of the smallest configuration was performed on 59 specimens at various levels of the mean static transverse tensile strength using an R ratio of 0.1 and a frequency of 20 Hz. A great deal of scatter was seen in the data. The majority of specimens failed near the center loading roller. To determine whether the scatter in the fatigue data is due to variability in raw material and/or the manufacturing process, additional testing should be performed on panels manufactured from different sources.

Peck, Ann W.↗