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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 163 records · Page 9

Individual Variability and Predictive Biomarkers of Human Sensitivity to Ionizing Radiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating personalized health risks from space radiation exposure requires understanding the factors underlying individual radiation sensitivity, which currently remain unknown. We started to address this challenge by identifying the genomic and demographic associations with sensitivity to low and high-LET ionizing radiation in the largest human sample cohort to date and by evaluating baseline DNA damage as a potential predictor of radiation responses. We have collected and irradiated peripheral blood mononuclear cells (PBMCs) from 768 healthy donors of matched ethnicity, 50/50 male/female, 18-70 years old. We have analyzed the responses of 576 donor PBMCs to irradiation with simulated galactic cosmic ray components: 350MeV/n 28Si, 350MeV/n 40Ar and 600MeV/n 56Fe, at 1.1 and 3 particles/100μm2 fluences, as well as 0.1Gy and 1Gy doses of gamma rays, at 4 and 24 hours post irradiation. We quantified post-irradiation DNA repair based on radiation-induced 53BP1+ foci formation, together with oxidative stress and cell death using a flow cytometry-based assay. We also assessed baseline levels of DNA repair in PBMCs at the time of sample collection prior to irradiation experiments. We observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We also identified a relationship between few DNA repair foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, baseline foci levels were positively associated with age and latent cytomegalovirus infection. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

Space radiation, human spaceflight, DNA damage↗

Monitoring Biomarkers for Muscular Atrophy Using an Electrochemical Chip for Astronaut Space Health

Skeletal muscle atrophy is a serious health problem for astronauts in long-duration space flight under microgravity conditions. Preventative measures against muscle atrophy require specific exercise and dietary regimens. Preemptive measurements to improve treatment have the potential to streamline these regimens, decreasing their daily footprint and increasing astronaut quality of life. The objective of our proposed project is to (1) develop a fully integrated disposable microelectrode array chip (with the size of a stamp) that can be interfaced with a handheld electronic system for simultaneous detection of the a panel of biomarkers to monitor the progression of skeletal muscle atrophy due to disuse under microgravity in long-duration spaceflights; and (2) use such quantitative information to guide the combined countermeasures of physical exercise and pharmaceuticals (i.e. specific protease inhibitors) so that the intensity, duration and frequency of exercise can be reduced. Note: The presentation includes voice commentary and plays best as a slide show. The voice begins once the presentation starts, and only requires the user to click to the next slide each time. With a run time of ~15 mins.

Biosensor↗

Monitoring Biomarkers for Muscular Atrophy using an Electronic Chip for Astronaut Health

Skeletal muscle atrophy is a serious health problem for astronauts in long-duration space flight under microgravity conditions. Preventative measures against muscle atrophy require specific exercise and dietary regimens. Preemptive measurements to improve treatment have the potential to streamline these regimens, decreasing their daily footprint and increasing astronaut quality of life. The objective of our proposed project is to (1) develop a fully integrated disposable microelectrode array chip (with the size of a stamp) that can be interfaced with a handheld electronic system for simultaneous detection of the a panel of biomarkers to monitor the progression of skeletal muscle atrophy due to disuse under microgravity in long-duration spaceflights; and (2) use such quantitative information to guide the combined countermeasures of physical exercise and pharmaceuticals (i.e. specific protease inhibitors) so that the intensity, duration and frequency of exercise can be reduced.

Biosensing↗

Biomarkers Detection With the Autonomous and Remotely Operated SOLID-LDChip Instrument in A Mars Drilling Simulating Campaign

One of the main goals in Mars exploration is to determine whether life has ever existed on the red planet. To achieve this goal, it is important to verify the performance, robustness, and maturity of instrumentation devoted to life detection, for example through field-testing in Mars analog environments.The Atacama Desert is considered one of the best terrestrial analogs of the surface of Mars due to abrupt temperature shifts, dryness, high UV radiation, and extremely low biomass. This, together with the lack of vegetation and the geochemistry of the regolith, make it an ideal scenario for testing instrumentation, performance, and concepts of operations. The Atacama Rover Astrobiology Drilling Studies (ARADS) is a NASA PSTAR project conceived for maturing and testing life-detection instrumentation in the Atacama Desert(1). The project is based on the K-REX2 rover equipped with a robotic 1-meter arm that delivers samples toon board instruments. This includes SOLID3.1 (Signs of Life Detector), designed as a life-detection instrument for finding complex organic molecules by means of the LDCHip (Life Detector Chip), an antibody microarray sensor(2). The instrument can extract organic compounds from soil, rocks, and sediments into a liquid solvent in the extraction cell (EC), allowing the search for hundreds of microbial molecular biomarkers at once (3). The robustness and reliability of SOLID were tested in the 2019 ARADS Mars drilling simulating campaign and confirmed with other analytical methods.

M Moreno-Paz↗

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates, with application to analysis of biomarker correlates in vaccine trials

Herein, this article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.

97 MATHEMATICS AND COMPUTING↗

Mucin 4 is a cellular biomarker of necrotizing bronchiolitis in influenza A virus infection

Influenza A virus (IAV) in the human and swine host infects epithelial cells lining the respiratory tract causing a necrotizing bronchitis and bronchiolitis. These epithelial surfaces are protected by large glycoproteins called mucins. Mucin 4 (MUC4) is a transmembrane mucin that consists of an alpha subunit responsible for surface protection and intracellular beta subunit involved in signal transduction which repress apoptosis and stimulate epithelial proliferation. This study was designed to determine the expression and potential role of MUC4 during IAV infection. We used immunohistochemistry in combination with machine learning image analysis to quantify differential protein expression of MUC4 subunits in IAV-infected and uninfected lung in a porcine model. MUC4 protein basal expression in control animals varied significantly by litter. MUC4 protein expression was significantly increased in bronchioles with necrotizing bronchiolitis compared to histologically normal bronchioles, likely representing a regenerative response to restore mucosal integrity of conducting airways. Understanding the impact of differential MUC4 expression among healthy individuals and during IAV infection will facilitate control strategies by elucidating mechanisms associated with susceptibility to IAV that can be therapeutically or genetically regulated and may be extended to other respiratory diseases.

60 APPLIED LIFE SCIENCES↗

G2PDeep-v2: A Web-Based Deep-Learning Framework for Phenotype Prediction and Biomarker Discovery for All Organisms Using Multi-Omics Data

Multi-omics data offers rich insights into complex traits across organisms, yet integrating and analyzing these datasets for phenotype prediction and marker discovery remains challenging. Researchers need accessible tools that combine deep learning, hyperparameter optimization, visualization, and downstream analysis in a unified web platform. To address this, we developed G2PDeep-v2, a web-based platform powered by deep learning for phenotype prediction and marker discovery from multi-omics data across a wide range of organisms, including humans and plants. The server provides multiple services for researchers to create deep-learning models through an interactive interface and train these models using an automated hyperparameter tuning algorithm on high-performance computing resources. Users can visualize the results of phenotype and markers predictions and perform Gene Set Enrichment Analysis for the significant markers to provide insights into the molecular mechanisms underlying complex diseases, conditions and other biological phenotypes being studied.

59 BASIC BIOLOGICAL SCIENCES↗

Biomarker and Geochemical Assay Validation in Mars Analog Sites: Lessons from the FELDSPAR (Field Exploration and Life Detection Sampling for Planetary Analog Research) Project

Missions looking for signs of life on other worlds can often only take a few samples once they arrive. Making sense of these "few and far between" observations is easier if we know what a "normal" level of variation for that kind of planet is. Recent eruption sites in Iceland are good places to learn about this, because they have very little life present and the same types of rocks as many places on Mars. We have visited several of these sites in Iceland and tested many different kinds of measurements: the energy available for life, the amount of DNA (an important biological molecule) present, the relative amounts of different kinds of micro-organisms, and the specific minerals that make up the rocks and ground. In addition to recommendations for future expeditions, we have also shown that using early on-site measurements to choose later on-site sample sites is very helpful in reducing the number of sample sites needed.

Geochemical Assay Validation↗

Space flight associated changes in astronauts’ plasma-derived small extracellular vesicle microRNA: Biomarker identification

This pilot study suggests relatively short (median 12 days long) low-Earth orbit (LEO) spaceflight induces changes in circulating plasma small extracellular vesicle (sEV) microRNA expression. Normalization of small RNA sequencing (sRNAseq) data and quantitative polymerase chain reaction (qPCR) validation confirmed miR-4732-3p is significantly upregulated up to 3 days post-landing, and enrichment analysis suggests this miRNA is expressed in various central nervous system tissues and hematopoietic cells and may be linked to different organ disorders.

60 APPLIED LIFE SCIENCES↗

Response of soil bacteria to PUREX chemicals suggests biomarker utility and bioremediation potential

Chemicals involved in plutonium uranium reduction extraction (PUREX) can be released from nuclear reprocessing facilities and accumulate in the environment. We exposed chemically diverse soils to a range of concentrations of key chemicals used in the PUREX process. The responses of soil microbial communities are dependent on soil type, and tributyl phosphate exposure generates the most reproducible changes in microbial communities. We reconstructed the genomes of key bacteria and find several phosphotriesterase genes found only in Rhizobiaceae. The abundance of phosphotriesterase genes is significantly higher in samples exposed to tributyl phosphate. In conclusion, these phosphotriesterase genes may be involved in breakdown of tributyl phosphate, and a means of accessing phosphate for these bacteria.

Bioremediation↗

Biomarkers of oxidative stress, diet and exercise distinguish soldiers selected and non-selected for special forces training

The metabolomic profiles of Soldiers entering the U.S. Special Forces Assessment and Selection course (SFAS) have not been evaluated. To compare pre-SFAS blood metabolomes of Soldiers selected during SFAS versus those not selected, and explore the relationships between the metabolome, physical performance, and diet quality. Fasted blood samples and food frequency questionnaires were collected from 761 Soldiers prior to entering SFAS to assess metabolomic profiles and diet quality, respectively. Physical performance was assessed throughout SFAS. Between-group differences (False Discovery Rate < 0.05) in 108 metabolites were detected. Selected candidates had higher levels of compounds within xenobiotic, pentose phosphate, and corticosteroid metabolic pathways, while non-selected candidates had higher levels of compounds potentially indicative of oxidative stress (i.e., sphingomyelins, acylcarnitines, glutathione, amino acids). Multiple compounds higher in non-selected versus selected candidates included: 1-carboxyethylphenylalanine; 4-hydroxy-nonenal-glutathione; α-hydroxyisocaproate; hexanoylcarnitine; sphingomyelin and were associated with lower diet quality and worse physical performance. Candidates selected during SFAS had higher pre-SFAS levels of circulating metabolites that were associated with resistance to oxidative stress, higher physical performance and higher diet quality. In contrast, non-selected candidates had higher levels of metabolites potentially indicating elevated oxidative stress. These findings indicate that Soldiers who were selected for continued Special Forces training enter the SFAS course with metabolites associated with healthier diets and better physical performance. Additionally, the non-selected candidates had higher levels of metabolites that may indicate elevated oxidative stress, which could result from poor nutrition, non-functional overreaching/overtraining, or incomplete recovery from previous physical activity.

59 BASIC BIOLOGICAL SCIENCES↗