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NASA NTRSDate not supplied

NASA GeneLab: The NASA Systems Biology Platform for Spaceomics Repository, Analysis and Visualization

At NASA Ames Research Center, the GeneLab Open Science Project is on a mission to gather all large -omics datasets relevant to space biology research. These datasets come from various organisms flown in multiple space habitats such as the International Space Station or the Space Shuttle, in addition to mimicking space-like conditions on ground. Researchers and citizen scientists all around the world have used the data and the analytical tools put together by the GeneLab team to start deciphering new biological impact of microgravity, space ionizing radiation and other space stressors.

GeneLab↗

NASA NTRS1990

Development of microcomputer-based mental acuity tests for repeated-measures studies

The purpose of this report is to detail the development of the Automated Performance Test System (APTS), a computer battery of mental acuity tests that can be used to assess human performance in the presence of toxic elements and environmental stressors. There were four objectives in the development of APTS. First, the technical requirements for developing APTS followed the tenets of the classical theory of mental tests which requires that tests meet set criteria like stability and reliability (the lack of which constitutes insensitivity). To be employed in the study of the exotic conditions of protracted space flight, a battery with multiple parallel forms is required. The second criteria was for the battery to have factorial multidimensionality and the third was for the battery to be sensitive to factors known to compromise performance. A fourth objective was for the tests to converge on the abilities entailed in mission specialist tasks. A series of studies is reported in which candidate APTS tests were subjected to an examination of their psychometric properties for repeated-measures testing. From this work, tests were selected that possessed the requisite metric properties of stability, reliability, and factor richness. In addition, studies are reported which demonstrate the predictive validity of the tests to holistic measures of intelligence.

Kennedy, R. S.↗

NASA NTRSDate not supplied

Supporting Crew Medical Decisions on Deep Space Missions: A Real-Time Performance Monitoring

Crewed missions into deep space will require astronauts to respond autonomously to safety- and time-critical anomalies. These and other potential issues will require the continuous monitoring and recognition of potentially subtle, but complex, anomalous data patterns. NASA continues to investigate real-time metrics for Extravehicular Operations1 and for providing feedback to improve performance2. Since it is unknown how long-term exposure to deep space will affect crew health, continuous monitoring of clinical and subclinical status is warranted. NASA is characterizing crew medical decision-support needs and identifying the recommended requirements of a Clinical Decision Support System (CDSS) within the Exploration Medical Capability Element (ExMC) of the Human Research Program3. Early detection, and continuous monitoring, of performance may provide an effective prognostic capability for assessing crew health state, and the identified requirements could be provided for an in-vehicle CDSS that acts as an assistant for delivering optimal health and performance and medical care during exploration missions. There is evidence to suggest that automatic, unobtrusive collection of keystroke features, such as alphanumeric key latencies, backspaces or typing rhythm, could be a valuable performance screening tool. Keystroke features show significant differences between control subjects and patients with overt clinical illness, such as multiple sclerosis4 and Parkinson’s disease5, as well as behavioral health and performance issues, such as mild cognitive impairment6 and depression7. This work is exploring a capability for the assessment of early task performance decline in crew as they perform daily activities. Timestamped keyboard entries are continuously collected and stored. Nominal keystroke interactions are compared to those obtained after exposure to spaceflight stressors, e.g., fatigue, to determine the methods sensitivity. This work will pave the way toward an objective detection tool that may be deployed in a spaceflight setting.

clinical↗

NASA NTRS2014

Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Schmidt, M. A.↗

NASA NTRS2019

Circulating miRNA Signature Predicts Health Risks Associated with Radiation and Microgravity

The many known health risks currently associated with space travel include increased risk of cardiovascular disease, cancer, central nervous system related diseases, muscle degeneration, and changes with host-gut microbiome interactions that can have profound impact with these and other health risks. The majority of the risk from space travel stem of the two components of the space environment which are microgravity and radiation. From our earlier work (Beheshti et al, PLOS One, 2018), we predicted that there is a systemic component of the host that causes general increased health risks due to spaceflight driven by a circulating microRNA (miRNA) signature consisting of 13 miRNAs that directly regulates both p53 and TGF1. MiRNAs are small non-coding RNA molecules with a negative and post-transcriptional regulation on gene expression) are increasingly recognized as major systemic regulators of responses to stressors, including microgravity, oxidative stress, and DNA damage. In addition, due to the size and stability of miRNAs, it is known that miRNAs can circulate throughout the body and have been found in the majority of the bodily fluids including blood, urine, saliva, and tears. Here, we start to dissect the actual impact of this miRNA signature on both the radiation and microgravity components and prove that this miRNA signature actually exists in the circulation of a host. To achieve this, we obtained multiple tissues including, serum, liver, and spleen and utilizing droplet digital PCR (ddPCR), we start to show how this circulating miRNA signature impacts which component of the spaceflight. The tissue was obtained from experiments performed on C57BL/6 male mice (N=10 for each condition) that were hindlimb unloaded (HU) to simulated microgravity, irradiated with 2Gy gamma (IR), HU plus IR, and control mice under normal conditions. It was shown that these miRNAs were present in the serum as predicted by the in silico prediction from our earlier predictions. The HU vs Controls show significant increases of the predicted miRNAs in the serum for more than half of the miRNA signature, with remaining miRNAs increasing comparing to the controls close to statistical significance. IR vs control mice showed increases for the miRNAs, but not has pronounced as the HU conditions. Finally, the combination of the HU+IR vs controls showed increases for the majority of the miRNA signature. The data indicates that the miRNA signature originally predicted through in silico methods is mainly associated with the microgravity component and is circulating throughout the host resulting in a systemic impact of the miRNAs on the host. These miRNAs are shown in the literature to potentially increase health risks associated with several diseases. In addition, we have begun testing the potential of utilizing antagonists to this miRNA signature to act as a potential countermeasure to mitigate radiation impact on the organism. This work demonstrates for the first time the potential of a minimally invasive novel biomarker and countermeasure that can be used to mitigate both radiation and microgravity effects.

Beheshti, Afshin↗

NASA NTRSDate not supplied

Crew Performance Support System to Aid in Anomaly Resolution: Concept of Operations

As missions progress into deep space, communication delays and disruptions will disenable the crew’s reliance on Earth experts. There are also limitations in the amount of data that can be downlinked to the ground. It is prudent to assume that critical, complex vehicle or habitat sub-systems will malfunction at a time when a lunar or Mars’ crew cannot rely on the Earth-Support team to detect, diagnose and resolve the problem and it is impractical to expect a small crew to step-in with the same level of expertise as 50+ authorities. The crew will need novel processes and advanced technological support to independently identify and resolve safety- and time-critical anomalies. That a self-reliant crew is unable to respond appropriately to time-critical anomalies is a significant risk to crew safety and mission success. This risk is driven by several factors; novel and unanticipated anomalies would not have been trained pre-flight, the crew could forget their pre-flight training or spaceflight stressors could impair the crew’s problem-solving ability. At last year’s IWS, Beard reported that a single spaceflight stressor (elevated CO2) could undermine the crew’s ability to independently respond to emergencies. Concept of Operations (ConOps) provide a common view of future system functions to all stakeholders. For the current project, a ConOps was developed that describes the operational processes, practices and capabilities needed by a crew of astronauts on deep space missions to autonomously respond to anticipated and unanticipated anomalies. It is crucial to recognize that, as of August 2018 existing technologies are unable to effectively support crew anomaly response to unanticipated events. “Intelligent technology” has not reached a maturity level that permits generalizing a solution to novel situations. For example, to train intelligent technology requires volumes of data that do not exist. The complexities involved in a manned mission to Mars cannot be compared to sending rovers to Mars using scripted software. This ConOps proposes a Crew Performance Support System (CPSS) that will push NASA and its industry partners toward what will be required for a safe and successful manned mission to Mars. Anomaly resolution during a deep space mission will take place within a dynamic, or changing, context. The figure to the left shows five broad contextual variables: the organizational culture, mission context, system characteristics, team characteristics and individual characteristics. The yellow arrow indicates that spaceflight and task-related stressors can affect system, team and individual crewmember characteristics and therefore anomaly response potential. The figure depicts a protective umbrella of Human-System Integration (HSI) principles that should be instituted during CPSS development including a balanced workload, shared situation awareness and building an appropriate level of trust in the automation. The figure also depicts two interrelated and cooperative components, an HSI Data System and other Enabling Capabilities will be required to support crew anomaly response and Earth-Support situation awareness. As we journey from ISS to Gateway to Mars, multiple, simultaneous and integrated research and development efforts (i.e., support systems co-evolution) must be implemented to meet the problem-solving challenges a self-reliant crew will face on a Mars’ mission. The crossovers between the capabilities are just as important as the discrete capabilities themselves. As the capabilities mature, the lines between the support subdomains will blur and an integrated system will emerge. The ConOps summarizes current knowledge about how highly trained people solve anomalies in safety- and time-critical situations, describes a group of capabilities that could help to reduce the extant risk and documents requirements levied on additional systems that provides critical inputs to the CPSS. Scenarios are used to promote a shared understanding of processes, practices and technological goals needed for safe and productive manned missions beyond LEO.

HSIA risk↗

NASA NTRS2021

Advancing Space Life Science Research Using Drosophila Melanogaster

As we embark on exploring deep space, it is imperative to unravel the impacts of such unique and dynamic environments on biological systems. Multiple studies using D. melanogaster, a well-established spaceflight model, have paved the way towards our understanding of spaceflight-associated health risks. Further, Drosophila quantitative genomic experiments along with improved automated hardware systems will enable efficient and effective identification of the underlying genetic and molecular determinants capable of physiological adaptation to endure harsh space environments.

Quantitative genomics↗

NASA NTRS1997

Autogenic-Feedback Training Exercise (AFTE) Method and System

The Autogenic-Feedback Training Exercise (AFTE) method of the present invention is a combined application of physiologic and perceptual training techniques. such as autogenic therapy and biofeedback. This combined therapy approach produces a methodology that is appreciably more effective than either of the individual techniques used separately. The AFTE method enables sufficient magnitude of control necessary to significantly reduce the behavioral and physiologic reactions to severe environmental stressors. It produces learned effects that are persistent over time and are resistant to extinction and it can be administered in a short period of time. The AFTE method may be used efficiently in several applications, among which are the following: to improve pilot and crew performance during emergency flying conditions; to train people to prevent the occurrence of nausea and vomiting associated with motion and sea sickness, or morning sickness in early pregnancy; as a training method for preventing or counteracting air-sickness symptoms in high-performance military aircraft; for use as a method for cardiovascular training, as well as for multiple other autonomic responses, which may contribute to the alleviation of Space Motion Sickness (SMS) in astronauts and cosmonauts; training people suffering from migraine or tension headaches to control peripheral blood flow and reduce forehead and/or trapezius muscle tension; training elderly people suffering from fecal incontinence to control their sphincter muscles; training cancer patients to reduce the nauseagenic effects of chemotherapy; and training patients with Chronic Intestinal Pseudo-obstruction (CIP).

Cowings, Patricia S.↗

NASA NTRS2016

NASA HRP Plans for Collaboration at the IBMP Ground-Based Experimental Facility (NEK)

NASA and IBMP are planning research collaborations using the IBMP Ground-based Experimental Facility (NEK). The NEK offers unique capabilities to study the effects of isolation on behavioral health and performance as it relates to spaceflight. The NEK is comprised of multiple interconnected modules that range in size from 50-250m(sup3). Modules can be included or excluded in a given mission allowing for flexibility of platform design. The NEK complex includes a Mission Control Center for communications and monitoring of crew members. In an effort to begin these collaborations, a 2-week mission is planned for 2017. In this mission, scientific studies will be conducted to assess facility capabilities in preparation for longer duration missions. A second follow-on 2-week mission may be planned for early in 2018. In future years, long duration missions of 4, 8 and 12 months are being considered. Missions will include scenarios that simulate for example, transit to and from asteroids, the moon, or other interplanetary travel. Mission operations will be structured to include stressors such as, high workloads, communication delays, and sleep deprivation. Studies completed at the NEK will support International Space Station expeditions, and future exploration missions. Topics studied will include communication, crew autonomy, cultural diversity, human factors, and medical capabilities.

Cromwell, Ronita L.↗

NASA NTRSDate not supplied

Extended Duration: The SIRIUS 21 Crew Perspective

The SIRIUS (Scientific International Research In a Unique terrestrial Station) missions represent a collaborative effort between NASA and Russia’s Institute for Biomedical Problems (IBMP) to conduct a series of long duration isolation and confinement spaceflight analog missions. Three missions of 17-day, 4-month, and 8-month duration (SIRIUS 17, 19, and 21) have been completed at IBMP’s Ground-Based Experimental Complex / Nazemnyy eksperimental'nyy kompleks (NEK) in Moscow, Russia. The international SIRIUS 21 crew comprising representatives from the United States, United Arab Emirates and Russia recently completed the 8-month analog lunar mission. The extended duration mission included simulated lunar transit, orbital, and surface operations with corresponding deep space communication delay, during which the crew participated in nearly 70 studies, eight of which were sponsored by NASA’s Human Research Program. The studies examined the effect of isolation and confinement on the behavioral health of research subjects, and investigated medical countermeasures, team performance, crew dynamics, crew autonomy, food system risks, consequences of confinement and associated physiological stressors. SIRIUS 21 crewmembers also participated in operational tasks such as Rover and CubeSat assembly, simulated lunar sample assessment, VR activities, robotic arm training, environmental systems monitoring, exercise, greenhouse maintenance and 3D printing. Communication with Mission Control was limited to 30-minute periods every two hours. Since access to the internet and email was restricted, simulated ground support provided the Crew’s primary source of daily news and mission information. This panel discussion will include presentations from the US SIRIUS 21 crewmembers – William Brown and Ashley Kowalski – about their experience participating in the mission and science. A facilitated question and answer session will follow with attendees encouraged to ask questions and join in discussion with the SIRIUS 21 crewmembers about their experiences. William Brown came to SIRIUS 21 with experience spread across multiple industries, including the military, defense contracting, healthcare consulting, software engineering, and logistics. He has lived in the Middle East, Central Asia, and Russia. A former Boren Scholar, Brown is fluent in Russian. He holds a Master of International Business degree from the University of South Carolina’s Darla Moore School of Business. Prior to that, he earned a bachelor’s degree in Russian language, literature, and culture from the University of South Carolina. There, he also completed additional undergraduate coursework in computer science. Ashley Kowalski is a Project Leader in The Aerospace Corporation’s International Partnerships Department, where she works with, represents, and provides technical support to the the U.S. Space Force Space Systems Command International Affairs (SSC/IA) office. Through her numerous national and international assignments (Russia, China, and Germany), she has worked on topics related to international space systems, national security space systems, civil systems (including human spaceflight and civil launch projects), space policy, satellite industry analysis, and satellite manufacturing start-ups. She is proficient in Russian and German, and fluent in Polish. Kowalski received her Bachelor of Science and Master of Science degrees in mechanical and aerospace engineering from George Washington University in 2011 and 2012, respectively.

S. E. Whiting↗

NASA NTRS2014

Recent Pharmacology Studies on the International Space Station

The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during long‐duration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.

Wotring, Virginia↗

NASA NTRS2008

Latent Herpes Viruses Reactivation in Astronauts

Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth's magnetosphere is particularly worrisome because it includes ionizing radiation from cosmic galactic radiation. Increased stress levels appear even before flight, presumably from the rigors of preflight training and the anticipation of the mission (12, 32, 38, 39). Space flight causes significant changes in human immune function (32), but the means by which these changes come about have been difficult to discern. Consistent indicators of stress associated with space flight include increased production of stress hormones, and changes in cells of the immune system. These changes include elevated white blood cell (WBC) and neutrophil counts at landing (15, 16, 35, 37). Activation of generalized stress responses before, during, and after space flight probably affects the function of the immune system. Space flight has been shown to decrease many aspects of immune function, including natural killer (NK) cell activity, interferon production, the blastogenic response of leukocytes to mitogens, cell-mediated immunity, neutrophil function and monocyte function (5, 16, 18, 21, 35-37).

Mehta, Satish K.↗

NASA NTRS2016

Instrumentation for Examining Microbial Response to Changes In Environmental Pressures

The Automated Adaptive Directed Evolution Chamber (AADEC) is a device that allows operators to generate a micro-scale analog of real world systems that can be used to model the local-scale effects of climate change on microbial ecosystems. The AADEC uses an artificial environment to expose cultures of micro-organisms to environmental pressures, such as UV-C radiation, chemical toxins, and temperature. The AADEC autonomously exposes micro-organisms to selection pressures. This improves upon standard manual laboratory techniques: the process can take place over a longer period of time, involve more stressors, implement real-time adjustments based on the state of the population, and minimize the risk of contamination. We currently use UV-C radiation as the main selection pressure, UV-C is well studied both for its cell and DNA damaging effects as a type of selection pressure and for its related effectiveness as a mutagen; having these functions united makes it a good choice for a proof of concept. The AADEC roadmap includes expansion to different selection pressures, including heavy metal toxicity, temperature, and other forms of radiation.The AADEC uses closed-loop control to feedback the current state of the culture to the AADEC controller that modifies selection pressure intensity during experimentation, in this case culture density and growth rate. Culture density and growth rate are determined by measuring the optical density of the culture using 600 nm light. An array of 600 nm LEDs illuminate the culture and photodiodes are used to measure the shadow on the opposite side of the chamber.Previous experiments showed that we can produce a million fold increase to UV-C radiation over seven iterations. The most recent implements a microfluidic system that can expose cultures to multiple different selection pressures, perform non-survival based selection, and autonomously perform hundreds of exposure cycles. A scalable pump system gives the ability to pump in various different growth media to individual cultures and introduce chemical toxins during experimentation; AADEC can perform freeze and thaw cycles. We improved our baseline characterization by building a custom UV-C exposure hood, a shutter operates on a preset timer allowing the user to set exposure intensity consistently for multiple iterations.

Environment↗

NASA NTRS2015

Omics Research on the International Space Station

The International Space Station (ISS) is an orbiting laboratory whose goals include advancing science and technology research. Completion of ISS assembly ushered a new era focused on utilization, encompassing multiple disciplines such as Biology and Biotechnology, Physical Sciences, Technology Development and Demonstration, Human Research, Earth and Space Sciences, and Educational Activities. The research complement planned for upcoming ISS Expeditions 45&46 includes several investigations in the new field of omics, which aims to collectively characterize sets of biomolecules (e.g., genomic, epigenomic, transcriptomic, proteomic, and metabolomic products) that translate into organismic structure and function. For example, Multi‐Omics is a JAXA investigation that analyzes human microbial metabolic cross‐talk in the space ecosystem by evaluating data from immune dysregulation biomarkers, metabolic profiles, and microbiota composition. The NASA OsteoOmics investigation studies gravitational regulation of osteoblast genomics and metabolism. Tissue Regeneration uses pan‐omics approaches with cells cultured in bioreactors to characterize factors involved in mammalian bone tissue regeneration in microgravity. Rodent Research‐3 includes an experiment that implements pan‐omics to evaluate therapeutically significant molecular circuits, markers, and biomaterials associated with microgravity wound healing and tissue regeneration in bone defective rodents. The JAXA Mouse Epigenetics investigation examines molecular alterations in organ specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight. Lastly, Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), NASA's first foray into human omics research, applies integrated analyses to assess biomolecular responses to physical, physiological, and environmental stressors associated with spaceflight.

Love, John↗

NASA NTRS2017

Mind the Gap: Exploring the Underground of the NASA Space Cancer Risk Model

The REID quantifies the lifetime risk of death from radiation-induced cancer in an exposed astronaut. The NASA Space Cancer Risk (NSCR) 2012 mode incorporates elements from physics, biology, epidemiology, and statistics to generate the REID distribution. The current model quantifies the space radiation environment, radiation quality, and dose-rate effects to estimate a NASA-weighted dose. This weighted dose is mapped to the excess risk of radiation-induced cancer mortality from acute exposures to gamma rays and then transferred to an astronaut population. Finally, the REID is determined by integrating this risk over the individual's lifetime. The calculated upper 95% confidence limit of the REID is used to restrict an astronaut's permissible mission duration (PMD) for a proposed mission. As a statistical quantity characterized by broad, subjective uncertainties, REID estimates for space missions result in wide distributions. Currently, the upper 95% confidence level is over 350% larger than the mean REID value, which can severely limit an astronaut's PMD. The model incorporates inputs from multiple scientific disciplines in the risk estimation process. Physics and particle transport models calculate how radiation moves through space, penetrates spacecraft, and makes its way to the human beings onboard. Epidemiological studies of exposures from atomic bombings, medical treatments, and power plants are used to quantify health risks from acute and chronic low linear energy transfer (LET) ionizing radiation. Biological studies in cellular and animal models using radiation at various LETs and energies inform quality metrics for ions present in space radiation. Statistical methodologies unite these elements, controlling for mathematical and scientific uncertainty and variability. Despite current progress, these research platforms contain knowledge gaps contributing to the large uncertainties still present in the model. The NASA Space Radiation Program Element (SRPE) defines the knowledge gaps that impact our understanding of the cancer risks. These gaps are outlined in NASA's Human Research Roadmap [4], which identifies the research questions and actions recommended for reducing the uncertainty in the current NSCR model and for formulation of future models. The greatest contributors to uncertainty in the current model include radiation quality, dose rate effects, and the transfer of exposure-based risk from other populations to an astronaut population. Future formulations of the risk model may benefit from including other potential sources of uncertainty such as space dosimetry, errors in human epidemiology data, and the impact of microgravity and other spaceflight stressors. Here, we discuss the current capabilities of the NSCR-2012 model and several immediate research needs, highlighting areas expected to have an operational impact on the current model schema. The following subway-style route map outlines the NSCR-2012 model (Green Line), emphasizing the research gaps in the Human Research Roadmap for risk of radiation-induced carcinogenesis (Stops on Dashed Lines). The map diagrams how these research gaps feed specific portions of the model.

Chappell, L. J.↗

NASA NTRSDate not supplied

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗

NASA NTRSDate not supplied

A Heritage BioSensor for Lunar Biology Experiments

Introduction: Automated biological experiments on small spacecraft missions have gained prominence over the past decade due to their simplicity, accessibility, and small mass, volume, and power needs. Most recently, the BioSensor microfluidic CubeSat payload aboard BioSentinel used an automated microfluidic cell culture system to study the effects of environmental stressors like deep space radiation and microgravity on yeast growth and metabolism. BioSentinel’s successor, the Lunar Explorer Instrument for space biology Applications (LEIA), will study the effects of lunar gravity and radiation using an improved version of the BioSensor microfluidic platform. The BioSensor payload has great adaptability to host a diverse range of biological experiments with single- and multi-celled organisms in both crewed and uncrewed missions, making it a compelling candidate for future space biology studies in a lunar surface environment. BioSensor Instrumentation on BioSentinel: The first spaceflight mission with the BioSensor, BioSentinel’s biology experiments occurred at three locations -- deep space, ISS and ground. The payload contained 18 microfluidic cards, each featuring 16 growth wells (a total of 288 growth wells). Each well was loaded before launch with desiccated yeast. In space, liquid culture medium (nutrients) was automatically introduced to batches of wells at a time to initiate a series of biology experiments. Temperature was maintained by thin film heaters on both sides of each card. Each well was equipped with three LEDs emitting at 570 nm, 630 nm, and 850 nm, paired with photodetectors to measure cell concentration and the alamarBlue (metabolic indicator dye) color transition from blue to pink. Phenotypic parameters like cell viability, metabolic rate, and generation time can be derived from these measurements. The sequence and timing of fluid fills, optical measurements, and thermal control were stored onboard, but could be updated asynchronously via ground communication. LEIA: LEIA is slated for launch no earlier than 2026 on a CLPS lander. BioSentinel’s BioSensor has been modified for use in LEIA. These improvements include: (a) storage for multiple culture medium types, (b) additional LED color (465 nm) for a new biological assay for antioxidant (carotenoid) production, (c) housing modifications for later biology load before launch, (d) improved isolation between electronic and fluidic components, and (e) improved humidity control for prolonged organism viability in case of post-load launch delay. Future Prospects: The consistent and successful demonstration of complex fluidics platforms alongside reliable instrument operations in a space environment is poised to create strong momentum for BioSensor-based biological experiment payloads. Planned future developments with the BioSensor include extending compatibility to a broader range of organisms and assays. Preliminary work has already demonstrated successful growth of Arabidopsis seedlings in fluidic cards. With a few modifications to the optical assembly, the setup could easily measure photosynthetic traits in plants and cyanobacteria. The addition of fluorescence measurements and generation of novel luminescent assays will elevate BioSensor’s functionality further. Beyond the BioSensor’s potential uses on free-flyer missions, ISS and Gateway, and CLPS landers, deploying the BioSensor to the lunar surface or in an artificial habitat on crewed missions could enable pioneering research on both how life responds to lunar conditions and future bioproduction capabilities making the BioSensor an indispensable tool for future space biology research.

Chinmayee Govinda Raj↗

NASA NTRSDate not supplied

Planetary Protection at Marshall Space Flight Center

Introduction: NASA Marshall Space Flight Center (MSFC) is historically known for its role in propulsion. While this is still the mainstay of MSFC’s expertise, many unique capabilities exist at MSFC which pertain to Planetary Protection (PP), including 1) identifying PP threats, and 2) developing novel methods to neutralize those threats. Furthermore, because these capabilities exist among diverse groups at MSFC, this work promotes collaboration both within and outside MSFC to expand and develop PP studies related to a full spectrum of NASA research, design, manufacture, and test interests. This abstract describes the PP research ongoing at MSFC and describes how it contributes to NASA’s overall PP objectives. Microbial Identification in Cleanrooms: One of the greatest threats to successful implementation of PP requirements is recontamination post bioburden reduction. One method to prevent recontamination is to keep the spacecraft in clean environments (i.e. cleanrooms) as much as possible during assembly and integration. However, cleanrooms are not without their own sources of contamination, which is why NASA is interested in monitoring the cleanliness of cleanrooms and characterizing the microbial species present. Such information allows a greater understanding of the resistance of these microbes to cleaning methods, as well as the risk of their contaminating the targeted planetary body of a given mission. MSFC has multiple cleanrooms of various ISO cleanliness levels onsite. We sampled the air and surfaces of three of these rooms, isolated microbes, and then sequenced the 16S rRNA gene or ITS region of the 18S rRNA gene for bacterial and fungal isolates, respectively. This has resulted in a microbial library which currently includes nearly 100 isolates. Microbial Enumeration of Spacecraft Materials: Currently, there are only a couple bioburden reduction methods approved by NASA, and often the harshness of these methods presents additional concerns or risks related to material properties. The goal of this research is to assess the microbial content of solid rocket motor (SRM) materials potentially used for lander missions. This work aims to more accurately define the risk of planetary contamination by providing empirical data associated with commonly used SRM raw materials. In this study, we pulverized nonmetallic SRM materials using a cryogenic grinder, then analyzed the resulting substrate for microbial colony forming units (CFU). We found that many SRM nonmetallic materials do not harbor detectable bioburden, though a range existed depending on the material. The results from this work provide quantitative data to potentially reduce concerns of contamination, while also providing a foundation for follow up studies into additional sterilization methods and molecular identification of contaminating microbes. Space Environmental Effects on Microbial Survival: One potential area of microbial reduction is the space environment. Understanding the survivability of hardy microbes in space-like conditions is a crucial first step in answering how space may reduce bioburden and if it can be relied upon for adherence to PP requirements. This work studied the effects of ultraviolet (UV) and ionizing radiation on survival of Bacillus atrophaeus spores. Microbes were dried on relevant polymeric materials then exposed to space environmental stressors. Coupons were submerged in water, diluted, and plated to determine survival compared with controls. We found that both UV and ionizing radiation were capable of reducing viability by nearly 99%, but there were still survivors, some with changed morphology indicating resistance mechanisms within certain cells. Manufacturing credit: Finally, given the above-mentioned limitations of the NASA-approved bioburden reduction methods, there is interest in understanding if manufacturing processes may provide enough bioburden reduction without additional PP-specific bakeouts. For instance, some material additives may be antimicrobial. Given this, we investigated the effects of several commonly used rubber additives on the growth of B. atrophaeus spores. We found that some of the materials inhibited growth of the spores, possibly supporting the use of these additives on missions with PP constraints. Future work into manufacturing credit for bioburden reduction includes inoculation of green insulation with B. atrophaeus spores, followed by a typical cure. Thermal profiles will be verified for appropriate temperature and durations to meet PP requirements, and cured samples will be analyzed using a cryogenic grinder to determine survivability of spores.

Chelsi D. Cassilly↗