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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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All sourcesNASA NTRSDOE OSTI
NASA NTRS2004

Biological Response to SPE Exposures

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Wilson, J. W.↗
NASA NTRS1995

Linear operating region in the ozone dial photon counting system

Ozone is a relatively unstable molecule found in Earth's atmosphere. An ozone molecule is made up of three atoms of oxygen. Depending on where ozone resides, it can protect or harm life on Earth. High in the atmosphere, about 15 miles up, ozone acts as a shield to protect Earth's surface from the sun's harmful ultraviolet radiation. Without this shield, we would be more susceptible to skin cancer, cataracts, and impaired immune systems. Closer to Earth, in the air we breathe, ozone is a harmful pollutant that causes damage to lung tissue and plants. Since the early 1980's, airborne lidar systems have been used for making measurements of ozone. The differential absorption lidar (DIAL) technique is used in the remote measurement of O3. This system allows the O3 to be measured as function of the range in the atmosphere. Two frequency-doubled Nd:YAG lasers are used to pump tunable dye lasers. The lasers are operating at 289 nm for the DIAL on-line wavelength of O3, and the other one is operated at 300 nm for the off-line wavelength. The DIAL wavelengths are produced in sequential laser pulses with a time separation of 300 micro s. The backscattered laser energy is collected by telescopes and measured using photon counting systems. The photon counting system measures the light signal by making use of the photon nature of light. The output pulse from the Photo-Multiplier Tube (PE), caused by a photon striking the PMT photo-cathode, is amplified and passed to a pulse height discriminator. The peak value of the pulse is compared to a reference voltage (discrimination level). If the pulse amplitude exceeds the discrimination level, the discriminator generates a standard pulse which is counted by the digital counter. Non-linearity in the system is caused by the overlapping of pulses and the finite response time of the electronics. At low count rates one expects the system to register one event for each output pulse from the PMT corresponding to a photon incident upon the photocathode, however, at higher rates the limitations of the discrimination/counting system will cause the observed count rate to be non-linear with respect to the true count rate. Depending on the pulse height distribution and the discriminator level, the overlapping of pulses (pulse pile-up) can cause count loss or even an additional apparent count gain as the signal levels increase. Characterization of the system, including the pulse height distribution, the signal to noise ratio, and the effect of the discriminator threshold level, is critical in maximizing the linear operating region of the system, thus greatly increasing the useful dynamic range of the system.

Andrawis, Madeleine↗
DOE OSTI2024

A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins

Abstract Metastasis is the leading cause of death in patients with cancer, driving considerable scientific and clinical interest in immunosurveillance of micrometastases. We investigated this process by creating a multiscale mathematical model to study the interactions between the immune system and the progression of micrometastases in general epithelial tissue. We analyzed the parameter space of the model using high-throughput computing resources to generate over 100,000 virtual patient trajectories. We demonstrated that the model could recapitulate a wide variety of virtual patient trajectories, including uncontrolled growth, partial response, and complete immune response to tumor growth. We classified the virtual patients and identified key patient parameters with the greatest effect on the simulated immunosurveillance. We highlight the lessons derived from this analysis and their impact on the nascent field of cancer patient digital twins (CPDTs). While CPDTs could enable clinicians to systematically dissect the complexity of cancer in each individual patient and inform treatment choices, our work shows that key challenges remain before we can reach this vision. In particular, we show that there remain considerable uncertainties in immune responses, unreliable patient stratification, and unpredictable personalized treatment. Nonetheless, we also show that in spite of these challenges, patient-specific models suggest strategies to increase control of clinically undetectable micrometastases even without complete parameter certainty.

Mathematical & Computational Biology↗
NASA NTRS2018

MPLA as an Innovative Immune Countermeasure

Spaceflight perturbs the human immune system. Among other manifestations, crewmembers may experience latent herpes viruses reactivation due to impaired lymphocyte function, as well as allergic/hypersensitivity reactions. Considering future space travel will be of longer duration (thereby increasing stress, exposure to radiation, etc…) with no rapid return option, it is of paramount importance to develop a countermeasure(s) to immune dysregulation. Monophosphoryl lipid A (MPLA) is a derivative of lipopolysaccharide (LPS), a potent inflammatory agent that can cause septic shock. MPLA possesses the immune-stimulatory effects of LPS without the adverse inflammatory effects. We hypothesize that treating immune cells with MPLA will boost their function enough to overcome the inhibitory effects of microgravity. While MPLA has been tested as an adjuvant extensively in mice and preliminarily for human vaccines, it has never been assessed for efficacy in microgravity.

Makedonas, George↗
NASA NTRSDate not supplied

Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

There are multiple Apollo program reports of lunar dust (LD) exposure leading to significant upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure, with associated eosinophilia indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study hypothesizes that LD exposure can alter susceptible individuals’ immune responses such that repeated exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. This will adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ helper and/or CD19+ B-cell mediated IgE production? To address these questions, a set of in-vitro cell culture experiments will be employed (short and long term) using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals, as well as established human basophil and mast cell lines. Cells will be co-cultured with cellular mitogens, common recall antigens (tetanus, Der p1), nickel (as a possible allergenic component of LD), with or without graded amounts of LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. The minimal amount of LD (Apollo 14 dust) and controls/simulants have been requested. This study, originally planned as an FY20/21 activity, was delayed due to the COVID pandemic. It is now scheduled to be performed during FY22.

Brian Crucian↗
NASA NTRSDate not supplied

Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

Although infrequent, there have been Apollo program reports of lunar dust (LD) exposure leading to notable upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure with associated eosinophilia, indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study with investigate if LD exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. Allergic reactivity could adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are to answer two questions: (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ T helper and/or CD19+ B-cell mediated IgE production? To address these questions, after the proposal and selection by NASA, our laboratory has separately requested and been approved for receipt of actual LD samples from the Apollo 16 mission. These samples will be used during the study to complete the proposed set of in vitro cell culture experiments (short and long term), using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals. Cells will be co-cultured with cellular mitogens, common recall antigens (Der p1), fine ground silica quartz (as a possible allergenic component of LD), or LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine, and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. A series of validation experiments was initiated in FY22 once the delivery of LD was received. Based on initial experimental findings, we are optimizing the culture conditions, LD concentrations, and refining our other protocol stimuli.

Audrie A. Colorado↗
NASA NTRSDate not supplied

Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

Although infrequent, there have been Apollo program reports of lunar dust (LD) exposure leading to notable upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure with associated eosinophilia, indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study with investigate if LD exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. Allergic reactivity could adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are to answer two questions: (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ T helper and/or CD19+ B-cell mediated IgE production? To address these questions, after the proposal and selection by NASA, our laboratory has separately requested and been approved for receipt of actual LD samples from the Apollo 16 mission. These samples will be used during the study to complete the proposed set of in vitro cell culture experiments (short and long term), using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals. Cells will be co-cultured with cellular mitogens, common recall antigens (Der p1), fine ground silica quartz (as a possible allergenic component of LD), or LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine, and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. A series of validation experiments was initiated in FY22 once the delivery of LD was received. Based on initial experimental findings, we are optimizing the culture conditions, LD concentrations, and refining our other protocol stimuli.

immunology↗
DOE OSTI2022

Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling

Background: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between ß cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by ß cells constitute an additional and biologically important mechanism for transmitting signals to adjacent ß cells or immune cells. Scope of Review: This review summarizes the general mechanisms of EV formation, with a particular focus on how lipids and lipid signaling pathways influence their formation and cargo. We review the implications of EV release from ß cells for T1D pathogenesis, how EVs and their cargo might be leveraged as biomarkers of the early events leading to T1D, and how EVs might be engineered as a therapeutic candidate to counter T1D outcomes. Major Conclusions: Islet ß cells have been viewed as initiators and propagators of the cellular circuit giving rise to autoimmunity in T1D. In this context, emerging literature suggests that EVs may represent a conduit for communication that holds more comprehensive messaging about the ß cells from which they arise. As the field of EV biology advances, it opens the possibility that intervening with EV formation and cargo loading could be a novel disease-modifying approach in T1D.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles

Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles. Here, we describe neutralizing mAbs isolated from mosaic-8b-immunized rabbits, some on par with Pemgarda, the only currently FDA-approved therapeutic mAb. Deep mutational scanning, in vitro selection of spike resistance mutations, and single-particle cryo-electron microscopy structures of spike–antibody complexes demonstrated targeting of conserved RBD epitopes. Rabbit mAbs included critical D-gene segment RBD-recognizing features in common with human anti-RBD mAbs, despite rabbit genomes lacking an equivalent human D-gene segment, thus demonstrating that the immune systems of humans and other mammals can utilize different antibody gene segments to arrive at similar modes of antigen recognition. These results suggest that animal models can be used to elicit anti-RBD mAbs with similar properties to those raised in humans, which can then be humanized for therapeutic use, and that mosaic RBD nanoparticle immunization coupled with multiplexed screening represents an efficient way to generate and select broadly cross-reactive therapeutic pan-sarbecovirus and pan-SARS-CoV-2 variant mAbs.

Science & Technology - Other Topics↗
NASA NTRSDate not supplied

Validation of Multisystem Countermeasures Protocol for Spaceflight during Antarctica Winter-over at Palmer Station (Palmer Countermeasures)

Stressors associated with spaceflight induce persistent immune compromise in astronauts which increase subclinical latent virus reactivation. In select crews, adverse clinical events have been documented. Antarctica winter-over (AWO) mission most closely reproduces these mission stressors: prolonged deployment, extreme environment, circadian misalignment, isolation, station lifestyle, and personal risk. The US maintains three primary stations in Antarctica: South Pole Station, McMurdo, and Palmer. Previous studies suggest that stations located near the interior of Antarctica (South Pole, McMurdo) have confounding effects on the immune system due to persistent hypobaric hypoxia. We hypothesized that winter-over at a coastal station (Palmer) would be more akin to spaceflight due to its normoxic but still extreme environment. Therefore, AWO at Palmer Station was selected, and validated in a pilot study, as the platform for testing and validating the effectiveness of an immune-restorative countermeasure protocol designed for deep space missions. Specifics include diet modifications, nutritional supplementation (vitamin D, probiotic, etc.), prescribed aerobic and resistive exercise, and a protocol of stress relieving virtual reality exercises. A multitude of biological sample types, including blood, saliva, and hair will be collected in tandem with the countermeasures in order to examine the combined effectiveness of the countermeasures. Samples and logs from subjects will be transported from Palmer Station to Johnson Space Center for further processing and distribution to co-investigators at the end of each winter-over. Extracted samples will be analyzed by appropriate testing platforms (Multiplex, qPCR, ELISA, etc.) to monitor alterations in leukocyte distribution, T cell and NK function, cytokine profiles, reactivation of latent herpesviruses, and nutritional factors. The data collected will be compared to a control year in which no countermeasures were deployed to evaluate the overall effectiveness of the analog and to validate the candidate immune countermeasure strategy. AWO 2023 concluded with the 4th in-mission timepoint conducted in September 2023. Samples for 16 subjects, including blood, saliva, hair, surveys, and PCR data, were all successfully returned from Antarctica to NASA/JSC mid-November 2023. Samples have since been distributed to co-investigators for further processing and analysis. With the completion of the first countermeasure year, preliminary data on the effectiveness of the deep-space protocol is being evaluated, however, no conclusions can be drawn yet until the completion of the second AWO countermeasure year, AWO 2024. AWO 2024 commenced in late-March 2024, with 13 subjects consenting and performing their baseline data collections (BDCs). Unique to the 2024 deployment, NSF lifted certain COVID restrictions and rallied the crewmembers in Punta Arenas, Chile. All NSF activities were transferred to this location and NASA was allowed, for the first time, to perform consent briefings, baseline samplings and training in person. This augment greatly increased the likelihood of success for the overwinter activities.

Cody L Gutierrez↗
NASA NTRSDate not supplied

Validation of Multisystem Countermeasures Protocol for Spaceflight during Antarctica Winter-over at Palmer Station (Palmer Countermeasures)

Stressors associated with spaceflight induce persistent immune compromise in astronauts which increase subclinical latent virus reactivation. In select crews, adverse clinical events have been documented. Antarctica winter-over (AWO) mission most closely reproduces these mission stressors: prolonged deployment, extreme environment, circadian misalignment, isolation, station lifestyle, and personal risk. The US maintains three primary stations in Antarctica: South Pole Station, McMurdo, and Palmer. Previous studies suggest that stations located near the interior of Antarctica (South Pole, McMurdo) have confounding effects on the immune system due to persistent hypobaric hypoxia. We hypothesized that winter-over at a coastal station (Palmer) would be more akin to spaceflight due to its normoxic but still extreme environment. Therefore, AWO at Palmer Station was selected, and validated in a pilot study [2], as the platform for testing and validating the effectiveness of an immune-restorative countermeasure protocol designed for deep space missions. Specifics include diet modifications, nutritional supplementation (vitamin D, probiotic, etc.), prescribed aerobic and resistive exercise, and a protocol of stress relieving virtual reality exercises. A multitude of biological sample types, including blood, saliva, and hair will be collected in tandem with the countermeasures in order to examine the combined effectiveness of the countermeasures. Samples and logs from subjects will be transported from Palmer Station to Johnson Space Center for further processing and distribution to co-investigators at the end of each winter-over. Extracted samples will be analyzed by appropriate testing platforms (Multiplex, qPCR, ELISA, etc.) to monitor alterations in leukocyte distribution, T cell and NK function, cytokine profiles, reactivation of latent herpesviruses, and nutritional factors. The data collected will be compared to a control year in which no countermeasures were deployed to evaluate the overall effectiveness of the analog and to validate the candidate immune countermeasure strategy. AWO 2023 concluded with the 4th in-mission timepoint conducted in September 2023. Samples for 16 subjects, including blood, saliva, hair, surveys, and PCR data, were all successfully returned from Antarctica to NASA/JSC mid-November 2023. Samples have since been distributed to co-investigators for further processing and analysis. With the completion of the first countermeasure year, preliminary data on the effectiveness of the deep-space protocol is being evaluated, however, no conclusions can be drawn yet until the completion of the second AWO countermeasure year, AWO 2024. AWO 2024 commenced in late-March 2024, with 13 subjects consenting and performing their baseline data collections (BDCs). Unique to the 2024 deployment, NSF lifted certain COVID restrictions and rallied the crewmembers in Punta Arenas, Chile. All NSF activities were transferred to this location and NASA was allowed, for the first time, to perform consent briefings, baseline samplings and training in person. This augment greatly increased the likelihood of success for the overwinter activities.

Cody L Gutierrez↗
DOE OSTI2021

Evolution of pathogen tolerance and emerging infections: A missing experimental paradigm

Researchers worldwide are repeatedly warning us against future zoonotic diseases resulting from humankind’s insurgence into natural ecosystems. The same zoonotic pathogens that cause severe infections in a human host frequently fail to produce any disease outcome in their natural hosts. What precise features of the immune system enable natural reservoirs to carry these pathogens so efficiently? To understand these effects, we highlight the importance of tracing the evolutionary basis of pathogen tolerance in reservoir hosts, while drawing implications from their diverse physiological and life-history traits, and ecological contexts of host-pathogen interactions. Long-term co-evolution might allow reservoir hosts to modulate immunity and evolve tolerance to zoonotic pathogens, increasing their circulation and infectious period. Such processes can also create a genetically diverse pathogen pool by allowing more mutations and genetic exchanges between circulating strains, thereby harboring rare alive-on-arrival variants with extended infectivity to new hosts (i.e., spillover). Finally, we end by underscoring the indispensability of a large multidisciplinary empirical framework to explore the proposed link between evolved tolerance, pathogen prevalence, and spillover in the wild.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2004

Effect of Microgravity on Mammalian Lymphocytes

The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization. The Astronauts will be exposed to microgravity environment for a long duration of time during these flights. Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system and nervous system. We did our preliminary investigations by exposing mammalian lymphocytes and astrocyte cells to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon, Inc. (USA).Our initial results showed no significant change in cytokine expression in these cells up to a time period of 120 hours exposure. Our future experiments will involve exposure for a longer period of time.

Banerjee, H.↗
NASA NTRS2002

Opportunities for nutritional amelioration of radiation-induced cellular damage

The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

Review↗
NASA NTRS1976

Bioprocessing development: Immune/cellular applications: Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

This space bioprocessing contract effort was comprised of four general objectives. These were: (1) the evaluation of current separation processes, (2) the identification of problems relevant to the separation of important biologicals, (3) the identification of ground-based assay methods needed for pre- and postflight analysis of space bioprocessing separation technology; and (4) the establishment of methods to determine the efficiency of space bioprocessing separation procedures. Immunology was deemed advantageous to study the diversity of cells and cell products involved and the extensive interest being given to their separation. Upon recognition of a cellular or molecular agent as foreign to the body, the immune system becomes activated to produce cells whose function is to destroy that agent and cell products whose function is to inactivate the agent and assist in its destruction. Long after the agent is removed from the body, some cells remain in a state of readiness to continue these destructive actions specifically against that agent should further exposure to it occur. This is the basis of acquired immunity to disease.

Twomey, J. J.↗
NASA NTRS2011

An Earthling to an Astronaut: Medical Challenges

Humans can travel safely into space in low Earth orbit (LEO) or to near-Earth objects if several medical, physiological, environmental, and human factors issues risks are mitigated. Research must be performed in order to set standards in these four areas, and current NASA standards are contained in the Space Flight Human System Standards volumes 1 and 2, and crew medical certification standards. These three sets of standards drive all of the clinical, biomedical research and environmental technology development for the NASA human space flight program. These standards also drive the identification of specific risks to crew health and safety, and we currently manage 65 human system risks within the human space flight program. Each risk has a specific program of research, technology development, and development of operational procedures to mitigate the risks. Some of the more important risks tat will be discussed in this talk include exposure to radiation, behavioral health due to confinement in a closed cabin, physiological changes such as loss of bone, muscle and exercise capability, reduction in immune system capability, environmental threats of maintaining an adequate atmosphere and water for drinking, avoidance of toxic or infectious material, protection of hearing, and human factors issues of equipment and task design. A nutritious and varied food supply must also be provided. All of these risks will be discussed and current strategies for mitigating these risks for long-duration human space flight. In mitigating these 65 human system risks, novel approaches to problem solving must be employed to find the most appropriate research and technology based applications. Some risk mitigations are developed internally to NASA while others are found through research grants, technology procurements, and more recently open innovation techniques to seek solutions from the global technical community. Examples and results will be presented from all of these approaches including the more recent use of prizes to stimulate innovation.

Davis, Jeffrey R.↗
DOE OSTI2025

Computational tools and data integration to accelerate vaccine development: challenges, opportunities, and future directions

The development of effective vaccines is crucial for combating current and emerging pathogens. Despite significant advances in the field of vaccine development there remain numerous challenges including the lack of standardized data reporting and curation practices, making it difficult to determine correlates of protection from experimental and clinical studies. Significant gaps in data and knowledge integration can hinder vaccine development which relies on a comprehensive understanding of the interplay between pathogens and the host immune system. In this review, we explore the current landscape of vaccine development, highlighting the computational challenges, limitations, and opportunities associated with integrating diverse data types for leveraging artificial intelligence (AI) and machine learning (ML) techniques in vaccine design. We discuss the role of natural language processing, semantic integration, and causal inference in extracting valuable insights from published literature and unstructured data sources, as well as the computational modeling of immune responses. Furthermore, we highlight specific challenges associated with uncertainty quantification in vaccine development and emphasize the importance of establishing standardized data formats and ontologies to facilitate the integration and analysis of heterogeneous data. Through data harmonization and integration, the development of safe and effective vaccines can be accelerated to improve public health outcomes. Looking to the future, we highlight the need for collaborative efforts among researchers, data scientists, and public health experts to realize the full potential of AI-assisted vaccine design and streamline the vaccine development process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses

Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro . The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.

59 BASIC BIOLOGICAL SCIENCES↗