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All sourcesNASA NTRSDOE OSTI
NASA NTRS2016

Expanded Benefits for Humanity from the International Space Station

In 2012, the International Space Station (ISS) partnership published the updated International Space Station Benefits for Humanity, 2nd edition, a compilation of stories about the many benefits being realized in the areas of human health, Earth observations and disaster response, and global education. This compilation has recently been revised to include updated statistics on the impacts of the benefits, and new benefits that have developed since the first publication. Two new sections have also been added to the book, economic development of space and innovative technology. This paper will summarize the updates on behalf of the ISS Program Science Forum, made up of senior science representatives across the international partnership. The new section on "Economic Development of Space" highlights case studies from public-private partnerships that are leading to a new economy in low earth orbit (LEO). Businesses provide both transportation to the ISS as well as some research facilities and services. These relationships promote a paradigm shift of government-funded, contractor-provided goods and services to commercially-provided goods purchased by government agencies. Other examples include commercial firms spending research and development dollars to conduct investigations on ISS and commercial service providers selling services directly to ISS users. This section provides examples of ISS as a test bed for new business relationships, and illustrates successful partnerships. The second new section, Innovative Technology, merges technology demonstration and physical science findings that promise to return Earth benefits through continued research. Robotic refueling concepts for life extensions of costly satellites in geo-synchronous orbit have applications to robotics in industry on Earth. Flame behavior experiments reveal insight into how fuel burns in microgravity leading to the possibility of improving engine efficiency on Earth. Nanostructures and smart fluids are examples of materials improvements that are being developed using data from ISS. The publication also expands the benefits of research results in human health, environmental change and disaster response and in education activities developed to capture student imaginations in support of science, technology, engineering and mathematics, or STEM, education internationally. Applications to human health of the knowledge gained on ISS continues to grow and improve healthcare technologies and our understanding of human physiology. Distinct benefits return to Earth from the only orbiting multi-disciplinary laboratory of its kind. The ISS is a stepping stone for future space exploration by providing findings that develop LEO and improve life on our planet.

Rai, Amelia↗
NASA NTRS2014

Assessing the Risk of Crew Injury Due to Dynamic Loads During Spaceflight

Spaceflight requires tremendous amounts of energy to achieve Earth orbit and to attain escape velocity for interplanetary missions. Although the majority of the energy is managed in such a way as to limit the accelerations on the crew, several mission phases may result in crew exposure to dynamic loads. In the automotive industry, risk of serious injury can be tolerated because the probability of a crash is remote each time a person enters a vehicle, resulting in a low total risk of injury. For spaceflight, the level of acceptable injury risk must be lower to achieve a low total risk of injury because the dynamic loads are expected on each flight. To mitigate the risk of injury due to dynamic loads, the NASA Human Research Program has developed a research plan to inform the knowledge gaps and develop relevant tools for assessing injury risk. The risk of injury due to dynamic loads can be further subdivided into extrinsic and intrinsic risk factors. Extrinsic risk factors include the vehicle dynamic profile, seat and restraint design, and spacesuit design. Human tolerance to loads varies considerably depending on the direction, amplitude, and rise-time of acceleration therefore the orientation of the body to the dynamic vector is critical to determining crew risk of injury. Although a particular vehicle dynamic profile may be safe for a particular design, the seat, restraint, and suit designs can affect the risk of injury due to localized effects. In addition, characteristics intrinsic to the crewmember may also contribute to the risk of injury, such as crewmember sex, age, anthropometry, and deconditioning due to spaceflight, and each astronaut may have a different risk profile because of these factors. The purpose of the research plan is to address any knowledge gaps in the risk factors to mitigate injury risk. Methods for assessing injury risk have been well documented in other analogous industries and include human volunteer testing, human exposure to dynamic environments, post-mortem human subject (PMHS) testing, animal testing, anthropomorphic test devices (ATD), dynamic models of the human, numerical models of ATDs, and numerical models of the human. Each has inherent strengths and limitations. For example, human volunteer testing is advantageous because a population can be selected that is similar to the astronaut corps; however, because of the inherent ethical limitations, only sub-injurious conditions can be tested. PMHSs can be tested in a variety of conditions including injurious levels, but the responses are not completely analogous to living human subjects. In addition, it is exceedingly difficult to select a PMHS population that is similar to the astronaut corps. ATDs are currently widely used in the automotive industry and military because they are highly repeatable and durable. Unfortunately, because they are mechanical models of the human body, the biofidelity of the responses are limited to dynamic conditions used to validate the ATD. Numerical models of the ATD, in addition to the strengths and limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional uncertainty. Dynamic models are simple and easy to use, but do not account for localized effects of the seat and suit. Finally, numerical models of the human have the potential to have the most advantages; however, the current models are not validated for the conditions expected during spaceflight. To properly assess spaceflight conditions with numerical human models, human data would be needed to optimize the model responses for those conditions. Using the appropriate assessment method with the knowledge gained for each risk factor, an appropriate approach for mitigating the risk of injury due to dynamic loads can be developed ensuring crew safety in future NASA vehicles.

Somers, J. T.↗
DOE OSTI2020

CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) affects the lives of 0.7–1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is lengthy and linked to significant toxicities; further, its efficacy is variable and resistant parasites are emerging. Shorter or lower dose antimonial treatment regimens, which would decrease the risk of adverse events and improve patient compliance, have shown reduced efficacy and further increase the risk emergence of antimonial-resistant strains. The progression of lesions in CL is partly determined by the immune response it elicits, and previous studies showed that administration of immunomodulatory type D CpG ODNs, magnifies the immune response to Leishmania and reduces lesion severity in nonhuman primates (NHP) challenged with Leishmania major or Leishmania amazonensis. Here we explored whether the addition of a single dose of immunomodulating CpG ODN D35 augments the efficacy of a short-course, low-dose pentavalent antimonial treatment regimen. Results show that macaques treated with D35 plus 5mg/kg sodium stibogluconate (SbV ) for 10 days had smaller lesions and reduced time to re-epithelization after infection with Leishmania major. No toxicities were evident during the studies, even at doses of D35 10 times higher than those used in treatment. Critically, pentavalent antimonial treatment did not modify the ability of D35 to induce type I IFNs. The findings support the efficacy of D35 as adjuvant therapy for shorter, low dose pentavalent antimonial treatment.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Toward Martian agriculture: responses of plants to hypobaria

The recent surge of interest in human missions to Mars has also generated considerable interest in the responses of plants to hypobaria (reduced atmospheric pressure), particularly among those in the advanced life support community. Potential for in situ resource utilization, challenges in meeting engineering constraints for mass and energy, the prospect of using lightweight plant growth structures on Mars, and the minimal literature on plant responses to low pressure all suggest much needed research in this area. However, the limited literature on hypobaria combined with previous findings on plant responses to atmospheric composition and established principles of mass transfer of gases suggest that some plants will be capable of tolerating and growing at pressures below 20 kPa; and for other species, perhaps as low as 5-10 kPa. In addition, normal and perhaps enhanced growth of many plants will likely occur at reduced partial pressures of oxygen (e.g., 5 kPa). Growth of plants at such low and partial pressures indicates the feasibility of cultivating plants in lightweight, transparent "greenhouses" on the surface of Mars or in other extraterrestrial or extreme environment locations. There are numerous, accessible terrestrial analogs for moderately low pressure ranges, but not for very low and extremely low atmospheric pressures. Research pertaining to very low pressures has been historically restricted to the use of vacuum chambers. Future research prospects, approaches, and priorities for plant growth experiments at low pressure are considered and discussed as they apply to prospects for Martian agriculture.

NASA Discipline Life Support Systems↗
DOE OSTI2021

The Relationship Between Perceived Control and Hypothalamic–Pituitary–Adrenal Axis Reactivity to the Trier Social Stress Test in Healthy Young Adults

Psychological factors can modulate the hypothalamic–pituitary–adrenal (HPA) axis activity toward stressors. Animal studies demonstrated that uncontrollability was one critical factor associated with HPA axis stress response, but the results in human studies were inconsistent. The current study adopted a standardized laboratory stress induction procedure, the Trier Social Stress Test (the TSST), as the stressor to regulate the objective controllability level, and young adult participants were asked to rate their subjectively perceived control level toward the stressor and measured their cortisol stress responses ( N =54; 19 females and 35 males) to address this concern. Results showed that participants’ perceived control on the TSST was related to the cortisol stress response. In other words, under the stress of a certain objective controllability level, the lower the subjectively perceived control level, the greater the HPA axis response. This finding suggested that, in addition to objective controllability, subjectively perceived control is a psychological factor that regulates activation of the HPA axis in young adults.

Liu, Qian↗
NASA NTRSDate not supplied

Enabling Advanced Air Mobility Operations through Appropriate Trust in Human-Autonomy Teaming: Foundational Research Approaches and Applications

Emerging Advanced Air Mobility(AAM)operations will be enabled by increasingly autonomous systems, requiring technologies to take on more responsibilities and fundamentally altering traditional human-automation interaction paradigms. The growing reliance on higher levels of automation will necessitate research to identify capabilities and principles that facilitate humans and machines working and thinking better together, i.e., human-autonomy teaming (HAT). Trust is an inherent requirement in effective teams because when members work interdependently, those agents (human, automation) must be willing to accept a level of risk to rely upon each other to reach goals and contribute to team tasks. This work provides an initial approach to enabling AAM operations through appropriate trust within HAT. The main contributions of this approach resides in connecting the construct of trust to mental models. Using the outlined mental model approach, we propose novel HAT strategies, such as Adaptive Trust Calibration, and preview planned research activities derived from this approach. Additionally, we propose several practical applications that can currently be employed by AAM development communities.

Eric T Chancey↗
NASA NTRSDate not supplied

Human Systems Risk Network - A Ranking Analysis of Risks

INTRODUCTION The Human Systems Risk Board (HSRB) is responsible for understanding, managing, and mitigating the risks associated with spaceflight. For a particular mission, the HSRB assigns each human system risk a rating on a 5x5 grid assessing its likelihood and consequence, which is ultimately used to compare and rank the risks. The HSRB approaches risk management by primarily establishing the context of each human system risk individually with the understanding that mitigating one risk might affect the likelihood, consequence, and mitigation approaches of another. To support this effort the HSRB, subject matter experts, and risk custodian teams created directed acyclic graphs (DAG), often called a causal graph, for the twenty-nine risks. In this presentation, we propose a new ranking algorithm for the risks which includes the downstream influence of each risk according to the information in the DAGs and provide an application of graph theoretic tools. METHODS In 2014, Mindock and Klaus proposed a taxonomy for human system risk influences which we have adopted to categorize the nodes in each DAG. Analyzing the nodes that correspond to the risks in this taxonomy allows us to analyze and understand how each risk influences the others. We construct an auxiliary network, which we call the Primary Risk Network (PRN), where the nodes are the twenty-nine space flight risks and, a directed edge connects Risk A to Risk B if Risk A has some influence on the likelihood or consequence of Risk B as described in the DAGS. We perform a variety of graph theoretic ranking methods on the nodes (or risks) in the PRN, including Katz centrality. RESULTS We rank the nodes in the PRN using the Katz centrality score. The ten risks with the highest score are pictured in Figure 1, colored (light to dark) according to their score. We analyze other centrality measures like betweenness centrality, eigenvector centrality, and the Estrada index, and provide the meaning of the corresponding rankings in terms of the risks. Future work includes analyzing the other categories in the taxonomy defined by Mindock and Klaus [1]. For example, we are interested in analyzing the nodes that are labeled as countermeasures or capabilities and perform similar analysis to measure their effect on certain medical conditions.

dag↗
NASA NTRS2013

Usability Evaluation of Spot and Runway Departure Advisor (SARDA) Concept in Dallas/Fort Worth Airport Tower Simulation

Spot and Runway Departure Advisor (SARDA) is a proposed decision-support tool for air traffic control tower controllers for reducing taxi delay and optimizing the departure sequence. In the present study, the tool's usability was evaluated to ensure that its claimed performance benefits are not being realized at the cost of increasing the work burden on controllers. For the evaluation, workload ratings and questionnaire responses collected during a human-in-the-loop simulation experiment were analyzed to assess the SARDA advisories' effects on the controllers' ratings on cognitive resources (e.g., workload, spare attention) and satisfaction. The results showed that SARDA reduced the controllers' workload and increased their spare attention. It also made workload and attention levels less susceptible to the effects of increases in the traffic load. The questionnaire responses suggested that the controllers generally were satisfied with the ease of use of the tool and the objectives of the SARDA concept, but with some caution. To gain more trust from controllers, the the reasoning behind advisories may need to be made more transparent to them.

human factors↗
NASA NTRSDate not supplied

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Critical mission tasks required by crews immediately after landing on a planetary surface include walking, jumping, and egressing from a seat. Understanding how these functional tasks are performed in partial gravity such as on the moon or Mars is necessary to define effective and comprehensive countermeasure strategies for preserving crew performance during exploration-class missions. We propose to study the performance of these tasks during the partial gravity phases of parabolic flight. These tasks will be performed using the same equipment and procedures as those used with astronauts returning from spaceflight and with ground-based subjects after prolonged axial body unloading during bed rest (sensorimotor standard measures). HYPOTHESIS We hypothesize that partial gravity during parabolic flight will cause acute changes in vestibular, proprioceptive, and sensorimotor functions, and these changes will impact the performance of mission critical tasks such as standing, walking, and jumping. The largest changes in performance are expected at the lowest gravity level (0.25g) because subjects will no longer be able to use the gravitational reference for the perception of upright. Ultimately, this information could be used to assess performance risks and inform the design of countermeasures for NASA exploration-class human missions. METHODS Twelve subjects will be tested during three flights of 30 parabolas, including 10 parabolas at 0.25g, 10 parabolas at 0.5g, and 10 parabolas at 0.75g. Subjects also will perform tests in 1g between parabolas. The tasks will be the same as those tested on astronauts returning from spaceflight: sit-to-stand with obstacle walk, tandem rail balance, jump down, and recovery from fall. Measurements will include: (a) time to test completion (sit-to-stand with obstacle walk, recovery from fall); (b) time elapsed between the start of motion and the stabilization of upright posture (recovery from fall, jump down); (c) mean sway speed during quiet standing (recovery from fall, jump down); (d) changes in heart rate and blood pressure (recovery from fall); (e) balance time and torso accelerations (tandem rail balance); (f) cone of stability (jump down); and (g) severity of motion sickness symptoms. RELEVANCE Although gravitational dose-response curves have been obtained for some biochemical systems in animals, these dose-responses are unknown for most human physiologic systems. Our study will compare the outcomes of four functional task tests in 0.25g, 0.5g, 0.75g, and 1g with those previously obtained in ground-based subjects after prolonged axial body unloading and in astronauts immediately after spaceflight. These comparisons will help us understand the true extent of functional task performance deficits in partial gravity. The dose-response relationship between gravity level and task performance decrement also will help determining the gravity threshold for these functional tasks. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element.

T. R. Macaulay↗
DOE OSTI2021

A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity

Viral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy. We hypothesized that modulation of TCA by incorporating a novel viral immunomodulatory factor into a viral vector may reduce unwanted TCA and immune responses during gene therapy. To test this hypothesis, we identified an immunomodulatory domain of the hepatitis C virus (HCV) NS protein 5A (NS5A) protein and studied the effect of viral vectors expressing NS5A peptide on TCA. Lentiviral vector-mediated expression of a short 20-mer peptide derived from the NS5A protein in human T cells was sufficient to inhibit TCA. Synthetic 20-mer NS5A peptide also inhibited TCA in primary human T cells. Mechanistically, the NS5A protein interacted with Lck and inhibited proximal TCR signaling. Importantly, NS5A peptide expression did not cause global T cell signaling dysfunction as distal T cell signaling was not inhibited. Finally, recombinant adeno-associated virus (AAV) vector expressing the 20-mer NS5A peptide reduced both the recall antigen and the TCR-mediated activation of human T cells and did not cause global T cell signaling dysfunction. Together, these data suggest that expression of a 20-mer NS5A peptide by an AAV vector may reduce unwanted TCA and may contribute to lower vector immunogenicity during gene therapy.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Critical mission tasks that are required by crews immediately after landing on a planetary surface are seat egress, jump, and walk. To be able to define an effective and comprehensive countermeasure strategy for preserving crew performance during exploration-class missions, there is a need to understand how these functional tasks are actually performed in partial gravity such as on the Moon or Mars. We propose to study the performance in the execution of these tasks during the partial gravity and hypergravity phases of parabolic flight. These tasks will be completed using the same equipment and procedures as the Standard Measures Sensorimotor protocol, which is performed by astronauts returning from spaceflight and by ground-based subjects after prolonged axial body unloading during bed rest. HYPOTHESIS We hypothesize that partial gravity during parabolic flight will cause acute changes in vestibular, proprioceptive, and sensorimotor functions, and these changes will impact the performance of mission critical tasks such as standing, walking, and jumping. The largest changes in performance are expected at the lowest gravity level (0.25g) because subjects will no longer be able to use the gravitational reference for the perception of vertical. Ultimately, this information could be used to assess performance risks and inform the design of countermeasures for NASA exploration-class human missions. METHODS Twelve subjects will be tested during three flights of 30 parabolas, including 10 parabolas at 0.25g, 10 parabolas at 0.5g and 10 parabolas at 0.75g. Subject also will perform tests in 1g between parabolas and in hypergravity (1.8g) during the pull-out phases. Subjects will perform the same tasks as those tested on astronauts returning from spaceflight: sit-to-stand and obstacle walk, tandem walk, jump down, and recovery from fall. Measurements will include: (a) the time for the subject to complete the test (sit-to-stand and obstacle walk, recovery from fall); (b) the time elapsed between the start of motion and the stabilization of upright posture (recovery from fall, jump down); (c) the mean sway speed during quiet standing (recovery from fall, jump down); (d) changes in heart rate and blood pressure (recovery from fall); (e) the percentage of correct steps and torso acceleration (tandem walk); and (f) the severity of motion sickness symptoms. RELEVANCE Although gravitational dose-response curves have been obtained for some biochemical systems in animals, these dose-responses are unknown for most human physiologic systems. Our study will compare the outcomes of 5 functional task tests in 0.25g, 0.5g, 0.75g, 1g, and 1.8g with those previously obtained in ground-based subjects after prolonged axial body unloading and in astronauts immediately after spaceflight. This comparison will help understanding the true extent of functional task performance deficits in partial gravity. The dose-response relationship between gravity level and task performance decrement also will help determining the gravity threshold for these functional tasks. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element

Gilles Clement↗
NASA NTRS2018

Updated Benefits for Humanity from the International Space Station

Final document is attached. In 2018, the International Space Station (ISS) [Figure 1] partnership completed a revision for the third edition of the International Space Station Benefits for Humanity, a compilation of case studies of benefits being realized from ISS activities in the areas of human health, Earth observations and disaster response, innovative technology, global education, and economic development of space. The revision included new assessments of economic value and scientific value with more detail than the second edition. The third edition contains updated statistics on the impacts of the benefits as well as new benefits that have developed since the previous publication. This presentation will summarize the updates on behalf of the ISS Program Science Forum, which consists of senior science representatives across the ISS international partnership. An independent consultant determined the economic valuation (EV) of ISS research benefits case studies and the third edition contains the results. The process involved a preliminary assessment of economic, social, and innovation factors. A more detailed assessment followed, which included factors such as addressable market, market penetration, revenue generation, ability to leverage across other applications or customer groups, quality of life improvements, health benefits, environmental benefits, cultural and community cohesion, inspiration, new knowledge, novel approaches, creation of a unique market niche, and research leadership. Because of the unique microgravity environment of the ISS laboratory, the multidisciplinary and international nature of the research, and the significance of the investment in its development, analyzing ISS scientific impacts is an exceptional challenge. As a result, the ISS partnership determined the scientific valuation (SV) of ISS research using a combination of citation analyses, bibliometrics, and narratives of important ISS utilization results. Approximately 2,100 ISS results publications comprised of scientific journal articles, conference proceedings, and gray literature, representing over 5,000 authors and co-authors on Earth were used in this evaluation to enable the communication of impacts of ISS research on various science and technology fields across many countries. The publication also updates and expands the previously described benefits of research results in the areas of space commerce, technology development, human health, environmental change and disaster response, and education activities. Distinct benefits return to Earth from the only orbiting multidisciplinary laboratory of its kind. The ISS is a stepping-stone for future space exploration while also providing findings that develop low Earth orbit as a place for sustained human activity and improve life on our planet.

research↗
NASA NTRS2018

Updated Benefits for Humanity, Third Edition (B4H3), from the International Space Station (ISS)

In 2018, the International Space Station (ISS) [Figure 1] partnership completed a revision for the third edition of the International Space Station Benefits for Humanity, a compilation of case studies of benefits being realized from ISS activities in the areas of human health, Earth observations and disaster response, innovative technology, global education, and economic development of space. The revision included new assessments of economic value and scientific value with more detail than the second edition. The third edition contains updated statistics on the impacts of the benefits as well as new benefits that have developed since the previous publication. This presentation will summarize the updates on behalf of the ISS Program Science Forum, which consists of senior science representatives across the ISS international partnership. An independent consultant determined the economic valuation (EV) of ISS research benefits case studies and the third edition contains the results. The process involved a preliminary assessment of economic, social, and innovation factors. A more detailed assessment followed, which included factors such as addressable market, market penetration, revenue generation, ability to leverage across other applications or customer groups, quality of life improvements, health benefits, environmental benefits, cultural and community cohesion, inspiration, new knowledge, novel approaches, creation of a unique market niche, and research leadership. Because of the unique microgravity environment of the ISS laboratory, the multidisciplinary and international nature of the research, and the significance of the investment in its development, analyzing ISS scientific impacts is an exceptional challenge. As a result, the ISS partnership determined the scientific valuation (SV) of ISS research using a combination of citation analyses, bibliometrics, and narratives of important ISS utilization results. Approximately 2,100 ISS results publications comprised of scientific journal articles, conference proceedings, and gray literature, representing over 5,000 authors and co-authors on Earth were used in this evaluation to enable the communication of impacts of ISS research on various science and technology fields across many countries. The publication also updates and expands the previously described benefits of research results in the areas of space commerce, technology development, human health, environmental change and disaster response, and education activities. Distinct benefits return to Earth from the only orbiting multidisciplinary laboratory of its kind. The ISS is a stepping-stone for future space exploration while also providing findings that develop low Earth orbit as a place for sustained human activity and improve life on our planet.

ISS↗
NASA NTRS1981

Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

NASA Program Biomedical Research↗
DOE OSTI2026

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↗
DOE OSTI2025

Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells

Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70-reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein–protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. As a result, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS1993

Training for life science experiments in space at the NASA Ames Research Center

As this country prepares for exploration to other planets, the need to understand the affects of long duration exposure to microgravity is evident. The National Aeronautics and Space Administration (NASA) Ames Research Center's Space Life Sciences Payloads Office is responsible for a number of non-human life sciences payloads on NASA's Space Shuttle's Spacelab. Included in this responsibility is the training of those individuals who will be conducting the experiments during flight, the astronauts. Preparing a crew to conduct such experiments requires training protocols that build on simple tasks. Once a defined degree of performance proficiency is met for each task, these tasks are combined to increase the complexity of the activities. As tasks are combined into in-flight operations, they are subjected to time constraints and the crew enhances their skills through repetition. The science objectives must be completely understood by the crew and are critical to the overall training program. Completion of the in-flight activities is proof of success. Because the crew is exposed to the background of early research and plans for post-flight analyses, they have a vested interest in the flight activities. The salient features of this training approach is that it allows for flexibility in implementation, consideration of individual differences, and a greater ability to retain experiment information. This training approach offers another effective alternative training tool to existing methodologies.

Rodrigues, Annette T.↗