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Configuring the HYSPLIT Model for National Weather Service Forecast Office and Spaceflight Meteorology Group Applications

The National Weather Service Forecast Office in Melbourne, FL (NWS MLB) is responsible for providing meteorological support to state and county emergency management agencies across East Central Florida in the event of incidents involving the significant release of harmful chemicals, radiation, and smoke from fires and/or toxic plumes into the atmosphere. NWS MLB uses the National Oceanic and Atmospheric Administration Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model to provide trajectory, concentration, and deposition guidance during such events. Accurate and timely guidance is critical for decision makers charged with protecting the health and well-being of populations at risk. Information that can describe the geographic extent of areas possibly affected by a hazardous release, as well as to indicate locations of primary concern, offer better opportunity for prompt and decisive action. In addition, forecasters at the NWS Spaceflight Meteorology Group (SMG) have expressed interest in using the HYSPLIT model to assist with Weather Flight Rules during Space Shuttle landing operations. In particular, SMG would provide low and mid-level HYSPLIT trajectory forecasts for cumulus clouds associated with smoke plumes, and high-level trajectory forecasts for thunderstorm anvils. Another potential benefit for both NWS MLB and SMG is using the HYSPLIT model concentration and deposition guidance in fog situations.

Dreher, Joseph↗

Investigating Biological Responses to Deep Space Radiation for Missions Beyond Low Earth Orbit (LEO) using Yeast

To enable long-term spaceflight missions and establish habitation on the Moon and Mars, we require a comprehensive understanding of the effects of chronic deep space radiation exposure on humans. BioSentinel is NASA’s first biological CubeSat to venture beyond Low Earth Orbit (LEO). It utilizes Saccharomyces cerevisiae (budding yeast) as a model organism to study biological responses to deep space radiation. Yeast share significant genetic homology with humans, including basic cellular metabolism and DNA repair mechanisms. In addition, unlike human cell cultures, yeast can survive the duration and constraints of a deep space mission. BioSentinel measures biological responses using an optical system and alamarBlue oxidation-reduction (redox) dye. Two strains of yeast are studied - a wild-type and a rad51 mutant strain that is deficient in DNA repair. Changes in metabolism and growth are monitored throughout the nominal 6-month mission. Preliminary tests indicate a significant change in the alamarBlue response to low-dose ionizing radiation (IR). Additionally, rad51 cells have shown an IR dose-dependent decrease in glucose uptake and accumulation of oxidized NADH (NAD+). These biomolecules are involved in reactions responsible for basic cell processes, including growth and development, signaling, and respiration. The current study expanded upon previous data by exposing yeast to deep space-relevant radiation. Glucose and NADH/NAD+ assays were conducted on yeast subjected to varying dosages of high-energy Fe-56 and simulated galactic cosmic rays (GCRs). The resulting data was analyzed using Excel and GraphPad Prism. A particular focus was to identify biomolecules resulting from aerobic respiration, which requires the presence of oxygen, or anaerobic processes. As long-term spaceflight missions draw near, it is increasingly important to characterize biological processes affected by the conditions of deep space. Studying biomolecular damage caused by deep space radiation may enable the development of engineering controls or biomedical therapeutics that mitigate health complications for future astronauts.

Kyra Keenan↗

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↗

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↗

Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

Convertino, V. A.↗

Development of Countermeasures to Aid Functional Egress from the Crew Exploration Vehicle Following Long Duration Spaceflight

Astronauts experience disturbances in sensorimotor function following their return to Earth due to adaptive responses that occur during exposure to the microgravity conditions of space flight. As part of the Crew Exploration Vehicle design requirements, the crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons in various sea state conditions following a water landing. The act of emergency egress includes and is not limited to rapid motor control tasks (including both fine motor such as object manipulation and gross motor such as opening a hatch) and visual acuity tasks while maintaining spatial orientation and postural stability in time to escape safely. Exposure to even low frequency motions (0.2-2.0 Hz) induced by sea conditions surrounding a vessel can cause significant fine and gross motor control problems affecting critical functions. These motion frequencies coupled with the varying sea state conditions (frequencies ranging from 0.125-0.5 Hz) cause performance deficits by affecting the efficacy of motor and visual acuity dependent skills in tasks critical to emergency egress activities such as visual monitoring of displays, actuating discrete controls, operating auxiliary equipment and communicating with Mission Control and recovery teams. Thus, during exploration class missions the sensorimotor disturbances due to the crewmember's adaptation to microgravity may lead to disruption in the ability to maintain postural stability and perform functional egress tasks during the initial introduction to the Earth's gravitational environment. At present, the functional implication of the interactions between a debilitated crewmember during readaptation to Earth s gravity and the environmental constraints imposed by a water landing scenario is not defined and no operational countermeasure has been implemented to mitigate this risk. Stochastic resonance (SR) is a mechanism whereby noise can assist and hence enhance the response of neural systems to relevant, subthreshold sensory signals. Application of subthreshold stochastic resonance noise coupled to sensory input either through the proprioceptive, visual or vestibular sensory systems, has been shown to improve motor function. Crew members who have adapted to microgravity have acquired new sensorimotor strategies that take time to discard. We hypothesize that detection of time-critical subthreshold sensory signals will play a crucial role in improving strategic responses and thus the rate of skill re-acquisition will be faster, leading to faster recovery of function during their re-adaptation to Earth G. Therefore, we expect the use of stochastic resonance mechanisms will enhance the acquisition of new strategic abilities. This process should ensure rapid restoration of functional egress capabilities during the initial return to Earth G after prolonged space flight. Therefore, the overall goals of this project are to investigate performance of motor and visual tasks during varying sea state conditions and develop a countermeasure based on stochastic resonance that could be implemented to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to Earth s gravity, allowing rapid CEV egress on water in varying sea states following long-duration space flight.

Mulavara, Ajitkumar↗

Plant Nitrogen Uptake Responses to Elevated Carbon Dioxide

Future long-duration missions will require a sustainable supply of food to support human crews. The spaceflight cabin environment often contains very high concentrations of CO 2 due to release of CO 2 by astronauts that is not completely scrubbed from the cabin, and it is therefore crucial to understand plant responses to elevated CO 2 (eCO 2 ) environments. Much focus has been given to changes in plant photosynthetic and performance parameters in response to eCO 2 , but the effects of eCO 2 on nitrogen (N) uptake are poorly understood. Shoot nitrate reduction may be reduced at eCO 2 , likely due to less reductant available for nitrate reduction because of reduced photorespiration and increased carbon fixation 1. Relative growth rate can be reduced at eCO 2 when N is provided only as nitrate and can be unaffected when N is supplied as ammonium. However, N uptake in response to eCO 2 has, to our knowledge, not yet been studied. An increased ‘preference’ for plants to take up N as ammonium at eCO 2 could have important implications for growth in the space environment, where N is currently only supplied as nitrate. In this study, novel stable isotope approaches were used in conjunction with hydroponics and isotope ratio mass spectrometry to determine the effect of eCO 2 on N preference for ammonium or nitrate in spring barley and lettuce when both N forms are provided equally. Several varieties of spring barley displayed increased ammonium preference at eCO 2 (720 ppm) compared to ambient CO 2 (410 ppm), though this was not true for all varieties. In most cases, increases in ammonium preference were driven by increases in ammonium uptake at eCO 2 and not decreases in nitrate uptake. Current research is assessing whether similar responses are observed in the candidate space crop lettuce, at levels of CO 2 like those observed on ISS (3000 ppm), and these results will also be presented. This work will enable the development of optimized nutrient regimes for candidate crops in space environments and the selection of crop varieties adapted to eCO 2 environments. Plants adapted to ammonium nutrition may play a role in future plant-based bioregenerative life support systems with higher ammonium concentrations due to waste recycling. Moreover, this research will further our understanding of plant responses to the eCO 2 environment brought about by climate change, allowing the development of future-proof crops that will help to maintain food security.

nitrogen↗

Investigating Neuro-Consequences of Spaceflight Using Drosophila Melanogaster

Research on human acclimation to spaceflight, including the recent NASA's Twin Study, reports complex effects of the spaceflight environment on health, with both acute and prolonged changes in multiple tissues. Spaceflight includes multiple factors such as microgravity, ionizing radiation, physiological stress, and disrupted circadian rhythms, that have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes on the nervous system. With 75% disease gene orthology to humans, short generation time, large sample size and ease of genetic, neuronal and behavioral studies, Drosophila is an excellent model to study nervous system dysfunction. Here, we present results from MVP-Fly-01 spaceflight mission that was launched on SpaceX CRS-14. The MVP hardware (developed by Techshot) used in this mission enabled us to have an in-flight 1g centrifuge, to distinguish the changes resulting from gravity versus those induced by other environmental factors associated with spaceflight. We observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown microgravity adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001) compared to in-flight 1g controls, suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.

Iyer, Janani↗

Effects of Altered Gravity on the Central Nervous System of Drosophila melanogaster

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. Spaceflight includes multiple factors such as microgravity, hypergravity, ionizing radiation, physiological stress, and disrupted circadian rhythms and these have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In terrestrial conditions, some of these factors can lead to cancer and neuroimmunological disorders. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes in the nervous system. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. To test this hypothesis, we used two experimental paradigms: 1) hypergravity, using the ground-based chronic acceleration model, and 2) spaceflight conditions, which includes exposure to microgravity and in-flight space 1g controls. In our ground studies, acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains. Additionally, we observed a depressed locomotor phenotype in these flies (p<0.05). These flies also show a decreased dopaminergic neuron counts in the fly brain upon exposure to acute hypergravity (p<0.05). Thus, the data suggest that altered gravity has a profound effect on the fly nervous system. Similarly, we observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001), suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.

nervous system↗

NASA Experience with Pogo in Human Spaceflight Vehicles

An overview of more than 45 years of NASA human spaceflight experience is presented with respect to the thrust axis vibration response of liquid fueled rockets known as pogo. A coupled structure and propulsion system instability, pogo can result in the impairment of the astronaut crew, an unplanned engine shutdown, loss of mission, or structural failure. The NASA history begins with the Gemini Program and adaptation of the USAF Titan II ballistic missile as a spacecraft launch vehicle. It continues with the pogo experienced on several Apollo-Saturn flights in both the first and second stages of flight. The defining moment for NASA s subsequent treatment of pogo occurred with the near failure of the second stage on the ascent of the Apollo 13 mission. Since that time NASA has had a strict "no pogo" philosophy that was applied to the development of the Space Shuttle. The "no pogo" philosophy lead to the first vehicle designed to be pogo-free from the beginning and the first development of an engine with an integral pogo suppression system. Now, more than 30 years later, NASA is developing two new launch vehicles, the Ares I crew launch vehicle propelling the Orion crew excursion vehicle, and the Ares V cargo launch vehicle. A new generation of engineers must again exercise NASA s system engineering method for pogo mitigation during design, development and verification.

Larsen, Curtis E.↗

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

biomechanics↗

The NASA Ames Life Sciences Data Archive: Biobanking for the Final Frontier

The NASA Ames Institutional Scientific Collection involves the Ames Life Sciences Data Archive (ALSDA) and a biospecimen repository, which are responsible for archiving information and non-human biospecimens collected from spaceflight and matching ground control experiments. The ALSDA also manages a biospecimen sharing program, performs curation and long-term storage operations, and facilitates distribution of biospecimens for research purposes via a public website (https:lsda.jsc.nasa.gov). As part of our best practices, a tissue viability testing plan has been developed for the repository, which will assess the quality of samples subjected to long-term storage. We expect that the test results will confirm usability of the samples, enable broader science community interest, and verify operational efficiency of the archives. This work will also support NASA open science initiatives and guides development of NASA directives and policy for curation of biological collections.

Biobank↗

The NASA Ames Research Center Institutional Scientific Collection: History, Best Practices and Scientific Opportunities

The NASA Ames Life Sciences Institutional Scientific Collection (ISC), which is composed of the Ames Life Sciences Data Archive (ALSDA) and the Biospecimen Storage Facility (BSF), is managed by the Space Biosciences Division and has been operational since 1993. The ALSDA is responsible for archiving information and animal biospecimens collected from life science spaceflight experiments and matching ground control experiments. Both fixed and frozen spaceflight and ground tissues are stored in the BSF within the ISC. The ALSDA also manages a Biospecimen Sharing Program, performs curation and long-term storage operations, and makes biospecimens available to the scientific community for research purposes via the Life Science Data Archive public website (https:lsda.jsc.nasa.gov). As part of our best practices, a viability testing plan has been developed for the ISC, which will assess the quality of archived samples. We expect that results from the viability testing will catalyze sample use, enable broader science community interest, and improve operational efficiency of the ISC. The current viability test plan focuses on generating disposition recommendations and is based on using ribonucleic acid (RNA) integrity number (RIN) scores as a criteria for measurement of biospecimen viablity for downstream functional analysis. The plan includes (1) sorting and identification of candidate samples, (2) conducting a statiscally-based power analysis to generate representaive cohorts from the population of stored biospecimens, (3) completion of RIN analysis on select samples, and (4) development of disposition recommendations based on the RIN scores. Results of this work will also support NASA open science initiatives and guides development of the NASA Scientific Collections Directive (a policy on best practices for curation of biological collections). Our RIN-based methodology for characterizing the quality of tissues stored in the ISC since the 1980s also creates unique scientific opportunities for temporal assessment across historical missions. Support from the NASA Space Biology Program and the NASA Human Research Program is gratefully acknowledged.

ALSDA↗

Trends in Human Spaceflight: Failure Tolerance, High Reliability and Correlated Failure History

In a half century of human spaceflight, NASA has continuously refined agency safety and reliability requirements in response to mission demands, critical failures, and technology development. Early spacecraft, including Mercury, Gemini and Apollo vehicles, were highly reliant on dissimilar redundancy and demonstrated test margins. Later programs, such as the reusable Space Transportation System (STS) and International Space Station (ISS), introduced probabilistic studies and isolated two-failure tolerance to improve robustness at the expense of added complexity. More recently, the Orion Multi-Program Crew Vehicle (MPCV) program adopted universal single-failure tolerance with two categorical exceptions; Zero-Failure Tolerant (0FT) and Design for Minimum Risk (DFMR) hardware. Failure tolerance variances are defined and managed in accordance with agency human-rating requirements, and require concurrence from program Technical Authorities (TA) as well as the MPCV Safety and Mission Assurance Safety and Engineering Review Panel (MSERP). To understand and reaffirm standards applied to Apollo, Space Shuttle and Orion vehicles, Orion and Deep Space Gateway Safety and Mission Assurance (S&MA) representatives conducted accelerated research to compare unique safety and reliability criteria against ground and flight anomalies, based on information contained in post-mission reports and the Problem Reporting and Corrective Action (PRACA) database. In some cases, high-profile failures and narrow escapes have reinforced decisions to maintain or adapt safety requirements. In others, empirical trends have highlighted the need for vigilance and innovative safety guidelines. Given the inability to achieve absolute compliance with evolving safety and reliability requirements, the team conducted a targeted review of DFMR and 0FT propulsion elements within the framework of changing system design, inspection, materials and process developments to formulate conclusions on technological maturity, failure density, and net changes in safety risk. Based on the aggregate performance of high-reliability and failure-tolerant systems, the authors have attempted to establish best practices and guidelines to inform future program decisions. On a somewhat cautionary note, this study is not intended to direct a universal set of requirements for future missions based on prior lessons learned. Spacecraft safety is a multi-variable problem, and attempts to mitigate past failures will not guarantee future success. However, this assessment offers a retrospective review of policy changes, implementation and effectiveness. In the future, NASA, European Space Agency (ESA) and industry partners may benefit from a more robust correlation between requirements and performance, as space-faring nations work toward more challenging, complex and long-duration commercial and deep-space ventures.

Green, Carrie↗

Effects of head-down bed rest on complex heart rate variability: Response to LBNP testing

Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 deg head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on a 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal 'complexity' (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ('chaos theory'), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.

Goldberger, Ary L.↗

Dermatitis during Spaceflight Associated with HSV-1 Reactivation

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.

Satish K. Mehta↗

Calmodulin-Dependent Protein Kinase mediates Hypergravity-Induced Changes in F-Actin Expression by Endothelial Cells

A number of basic cellular functions, e.g., electrolyte concentration cell growth rate, glucose utilization, bone formation, response to growth stimulation and exocytosis are modified by microgravity or during spaceflight. Studies with intact animal during spaceflights have found lipid accumulations within the lumen of the vasculature and degeneration of the vascular wall. Capillary alterations with extensive endothelial invaginations were also seen. Hemodynamic studies have shown that there is a redistribution of blood from the lower extremities to the upper part of the body; this will alter vascular permeability, resulting in leakage into surrounding tissues. These studies indicate that changes in gravity will affect a number of physiological systems, including the vasculature. However, few studies have addressed the effect of microgravity on vascular cell function and metabolism. A major problem with ground based studies is that achieving a true microgravity hand, environment for prolonged period is not possible. On the other increasing gravity (i.e., hypergravity) is easily achieved. Several researchers have shown that hypergravity will increase the proliferation of several different cell limes (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies suggest that hypergravity will alter the behavior of most cells. Several investigators have shown that hypergravity affects the expression of the early response genes (c-fos and c-myc) and the activation of several protein kinases (PK's) in cells (10,11). In this study we investigated whether hypergravity alters the expression of f-actin by aortic endothelial cells, and the possible role of protein kinases (calmodulin(II)-dependent and PKA) as mediators of these effects.

Love, Felisha D.↗

Stretch Reflex as a Simple Measure to Evaluate the Efficacy of Potential Flight Countermeasures Using the Bed Rest Environment

INTRODUCTION: Spaceflight is acknowledged to have significant effects on the major postural muscles. However, it has been difficult to separate the effects of ascending somatosensory changes caused by the unloading of these muscles during flight from changes in sensorimotor function caused by a descending vestibulo-cerebellar response to microgravity. It is hypothesized that bed rest is an adequate model to investigate postural muscle unloading given that spaceflight and bed rest may produce similar results in both nerve axon and muscle tissue. METHODS: To investigate this hypothesis, stretch reflexes were measured on 18 subjects who spent 60 to 90 days in continuous 6 head-down bed rest. Using a motorized system capable of rotating the foot around the ankle joint (dorsiflexion) through an angle of 10 deg at a peak velocity of approximately 250 deg/sec, a stretch reflex was recorded from the subject's left triceps surae muscle group. Using surface electromyography, about 300 reflex responses were obtained and ensemble-averaged on 3 separate days before bed rest, 3 to 4 times in bed, and 3 times after bed rest. The averaged responses for each test day were examined for reflex latency and conduction velocity (CV) across gender and compared with spaceflight data. RESULTS: Although no gender differences were found, bed rest induced changes in reflex latency and CV similar to the ones observed during spaceflight. Also, a relationship between CV and loss of muscle strength in the lower leg was observed for most bed rest subjects. CONCLUSION: Even though bed rest (limb unloading) alone may not mimic all of the synaptic and muscle tissue loss that is observed as a result of spaceflight, it can serve as a working analog of flight for the evaluation of potential countermeasures that may be beneficial in mitigating unwanted changes in the major postural muscles that are observed post flight.

Cerisano, J. M.↗