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Payload Hardware and Experimental Protocol for Testing the Effect of Space Microgravity on the Resistance to Gentamicin of Stationary-Phase Uropathogenic Escherichia Coli and Its Sigma (sup S)-Deficient Mutant

Human immune response is compromised and bacteria can become more antibiotic resistant in space microgravity (MG). We report that under low-shear modeled microgravity (LSMMG) stationary-phase uropathogenic Escherichia coli (UPEC) become more resistant to gentamicin (Gm). UPEC causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a standard treatment, so these findings could impact astronaut health. Because LSMMG has been shown to differ from MG, we report here preparations to examine UPEC's Gm sensitivity during spaceflight using the E. coli Anti-Microbial Satellite (EcAMSat) on a free flying nanosatellite in low Earth orbit. Within EcAMSats payload, a 48-microwell fluidic card contains and supports study of bacterial cultures at constant temperature; optical absorbance changes in cell suspensions are made at three wavelengths for each microwell and a fluid-delivery system provides growth medium and predefined Gm concentrations. Performance characterization is reported for spaceflight prototypes of this payload system. Using conventional microtiter plates, we show that Alamar Blue (AB) absorbance changes due to cellular metabolism accurately reflect E. coli viability changes: measuring AB absorbance onboard EcAMSat will enable telemetry of spaceflight data to Earth. Laboratory results using payload prototypes are consistent with wellplate and flask findings of differential sensitivity of UPEC and its delta rpoS strain to Gm. Space MG studies using EcAMSat should clarify inconsistencies from previous space experiments on bacterial antibiotic sensitivity. Further, if sigma (sup s) plays the same role in space MG as in LSMMG and Earth gravity, EcAMSat results would facilitate utilizing our previously developed terrestrial UTI countermeasures in astronauts.

Matin, A. C.↗

Informing climate adaptation strategies using ecological simulation models and spatial decision support tools

Introduction: Forest landscapes offer resources and ecosystem services that are vital to the social, economic, and cultural well-being of human communities, but managing for these provisions can require socially and ecologically relevant trade-offs. We designed a spatial decision support model to reveal trade-offs and synergies between ecosystem services in a large eastern Cascade Mountain landscape in Washington State, USA. Methods: We used process-based forest landscape (LANDIS-II) and hydrology (DHSVM) models to compare outcomes associated with 100 years of simulated forest and wildfire dynamics for two management scenarios, Wildfire only and Wildfire + Treatments. We then examined the strength and spatial distribution of potential treatment effects and trends in a set of resources and ecosystem services over the simulation period. Results: We found that wildfire area burned increased over time, but some impacts could be mitigated by adaptation treatments. Treatment benefits were not limited to treated areas. Interestingly, we observed neighborhood benefits where fire spread and severity were reduced not only in treated patches but in adjacent patches and landscapes as well, creating potential synergies among some resource benefits and services. Ordinations provided further evidence for two main kinds of outcomes. Positive ecological effects of treatments were greatest in upper elevation moist and cold forests, while positive benefits to human communities were aligned with drier, low- and mid-elevation forests closer to the wildland urban interface. Discussion: Our results contribute to improved understanding of synergies and tradeoffs linked to adaptation and restoration efforts in fire-prone forests and can be used to inform management aimed at rebuilding resilient, climate-adapted landscapes.

54 ENVIRONMENTAL SCIENCES↗

Spatiotemporal dynamics of ecosystem fires and biomass burning-induced carbon emissions in China over the past two decades

Fire is a major type of disturbance that has important influences on ecosystem dynamics and carbon cycles. Yet our understanding of ecosystem fires and their carbon cycle consequences is still limited, largely due to the difficulty of large-scale fire monitoring and the complex interactions between fire, vegetation, climate, and anthropogenic factors. Here, using data from satellite-derived fire observations and ecosystem model simulations, we performed a comprehensive investigation of the spatial and temporal dynamics of China's ecosystem fire disturbances and their carbon emissions over the past two decades (1997–2016). Satellite-derived results showed that on average about 3.47 - 4.53 x 10 4 km 2 of the land was burned annually during the past two decades, among which annual burned forest area was about 0.81 - 1.25 × 10 4 km 2 , accounting for 0.33-0.51% of the forest area in China. Biomass burning emitted about 23.02 TgC per year. Compared to satellite products, simulations from the Energy Exascale Earth System Land Model (ELM) strongly overestimated China's burned area and fire-induced carbon emissions. Annual burned area and fire-induced carbon emissions were high for boreal forest in Northeast China's Daxing'anling region and subtropical dry forest in South Yunnan, as revealed by both the satellite product and the model simulations. Our results suggest that climate and anthropogenic factors play critical roles in controlling the spatial and seasonal distribution of China's ecosystem fire disturbances. Our findings highlight the importance of multiple complementary approaches in assessing ecosystem fire disturbance and its carbon consequences. Further studies are required to improve the methods of observing and modelling China's ecosystem fire disturbances, which will provide valuable information for fire management and ecosystem sustainability in an era when both human activities and the natural environment are rapidly changing.

54 ENVIRONMENTAL SCIENCES↗

Recommendations from NASA's Operational and Research Musculoskeletal Summit

Introduction: Continuously evolving medical standards of care, limited crew training time, and the inherent constraints of space flight necessitate regular revisions of the mission medical support infrastructure and methodology. A three-day Operational and Research Musculoskeletal Summit was held to review NASA s current strategy for preflight health maintenance and injury screening, risk mitigation for musculoskeletal injuries or syndromes, treatment methods during flight, and research topics to mitigate risks to astronaut health. The Summit also undertook consideration of the best evidence-based terrestrial musculoskeletal practices to recommend their adaptation for use in space. Methods: The types and frequencies of musculoskeletal injuries sustained by short- and long-duration astronauts were obtained from the Longitudinal Study of Astronaut Health. The Summit panel was comprised of experts from the clinical and research communities, as well as representatives from NASA Headquarters, the Astronaut corps, and the offices of JSC Medical Operations, JSC Human Adaptation and Countermeasures, Glenn Research Center Human Research, and Astronaut Strength Conditioning and Rehabilitation. Before the summit, panelists participated in a Web-based review of NASA s Space Medical Conditions List (SMCL). Results: The Summit generated seventy-five operational and research recommendations to the NASA Office of Space Medicine, including changes to the SMCL and to the musculoskeletal section of the ISS debrief questionnaire. From these recommendations, seven were assigned highest value and priority, and could be immediately adopted for the exploration architecture. Discussion: Optimized exercise and conditioning to improve performance and forestall musculoskeletal damage on orbit were the primary area of focus. Special attention was paid to exercise timing and muscle group specificity. The panel s recommendations are currently in various stages of consideration or integration into the ISS and Exploration programs. This effort serves to enhance the on-orbit system so comprehensive treatment can be delivered in a more effective and standardized manner.

Jones, J. A.↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).

Radiation effects↗

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. Here we investigate use of mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, for assessment of space radiation damage. In a pilot study, we use PXB mice whose livers contain >90% human cells and have been found to function nearly identically to human liver tissues. These mice were exposed to gamma rays for investigations of DNA damage, transcriptomics, and histopathological changes in the humanized livers. Results obtained from PXB mice were compared non-engrafted control animals from the same background strain that are exposed to identical conditions. Preliminary data from histopathological analysis suggest chimeric mouse models are suitable for investigations of space radiation risks, as the humanized liver tissue exhibited changes induced by radiation and was markedly distinct from the liver tissue from the control animals (Fox Chase SCID mice).

Radiation effects↗

Artificial intelligence approaches to software engineering

Artificial intelligence approaches to software engineering are examined. The software development life cycle is a sequence of not so well-defined phases. Improved techniques for developing systems have been formulated over the past 15 years, but pressure continues to attempt to reduce current costs. Software development technology seems to be standing still. The primary objective of the knowledge-based approach to software development presented in this paper is to avoid problem areas that lead to schedule slippages, cost overruns, or software products that fall short of their desired goals. Identifying and resolving software problems early, often in the phase in which they first occur, has been shown to contribute significantly to reducing risks in software development. Software development is not a mechanical process but a basic human activity. It requires clear thinking, work, and rework to be successful. The artificial intelligence approaches to software engineering presented support the software development life cycle through the use of software development techniques and methodologies in terms of changing current practices and methods. These should be replaced by better techniques that that improve the process of of software development and the quality of the resulting products. The software development process can be structured into well-defined steps, of which the interfaces are standardized, supported and checked by automated procedures that provide error detection, production of the documentation and ultimately support the actual design of complex programs.

Johannes, James D.↗

The Tropical Rainfall Measuring (TRMM) - What Have We Learned and What Does the Future Hold?

Rainfall is important in the hydrological cycle and to the lives and welfare of humans. In addition to being a life-giving resource, rainfall processes also plays a crucial role in the dynamics of the global atmospheric circulation. Three-fourths of the energy that drives the atmospheric wind circulation comes from the latent heat released by tropical precipitation. It varies greatly in space and time. The rain-producing cloud systems may last several hours or days. Their dimensions range from 10 km to several hundred km. This makes it difficult to incorporate rainfall directly large-scale weather and climate models. Until the end of 1997, precipitation in the global tropics was not known to within a factor of two. Regarding "global warming", the various large-scale models differed among themselves in the predicted magnitude of the warming and in the expected regional effects of these temperature and moisture changes. The Tropical Rainfall Measuring Mission (TRMM) satellite has yielded important interim results related to rainfall observations, data assimilation and model forecast skills when rainfall data is assimilated. This talk will summarize where the TRMM science team is with regards to answering some of these important scientific challenges, as well as discuss the future Global Precipitation Mission which will provide 3 hourly rainfall coverage and offers some unique collaborative potential for NOAA and NASA.

Kummerow, C.↗

Ground Processing Affordability for Space Vehicles

Launch vehicles and most of their payloads spend the majority of their time on the ground. The cost of ground operations is very high. So, why so often is so little attention given to ground processing during development? The current global space industry and economic environment are driving more need for efficiencies to save time and money. Affordability and sustainability are more important now than ever. We can not continue to treat space vehicles as mere science projects. More RLV's (Reusable Launch Vehicles) are being developed for the gains of reusability which are not available for ELV's (Expendable Launch Vehicles). More human-rated vehicles are being developed, with the retirement of the Space Shuttles, and for a new global space race, yet these cost more than the many unmanned vehicles of today. We can learn many lessons on affordability from RLV's. DFO (Design for Operations) considers ground operations during design, development, and manufacturing-before the first flight. This is often minimized for space vehicles, but is very important. Vehicles are designed for launch and mission operations. You will not be able to do it again if it is too slow or costly to get there. Many times, technology changes faster than space products such that what is launched includes outdated features, thus reducing competitiveness. Ground operations must be considered for the full product Lifecycle, from concept to retirement. Once manufactured, launch vehicles along with their payloads and launch systems require a long path of processing before launch. Initial assembly and testing always discover problems to address. A solid integration program is essential to minimize these impacts, as was seen in the Constellation Ares I-X test rocket. For RLV's, landing/recovery and post-flight turnaround activities are performed. Multi-use vehicles require reconfiguration. MRO (Maintenance, Repair, and Overhaul) must be well-planned--- even for the unplanned problems. Defect limits and standard repairs need to be in-place as well as easily added. Many routine inspections and maintenance can be like an aircraft overhaul. Modifications and technology upgrades should be expected. Another factor affecting ground operations efficiency is trending. It is essential for RLV's, and also useful for ELV's which fly the same or similar models again. Good data analysis of technical and processing performance will determine fixes and improvements needed for safety, design, and future processing. Collecting such data on new or low-frequency vehicles is a challenge. Lessons can be learned from the Space Shuttle, or even the Concorde aircraft. For all of the above topics, efficient business systems must be established for comprehensive program management and good throughput. Drawings, specifications, and manuals for an entire launch vehicle are often in different formats from multiple vendors, plus they have proprietary constraints. Nonetheless, the integration team must ensure that all data needed is compatible and visible to each appropriate team member. Ground processing systems for scheduling, tracking, problem resolution, etc. must be well laid-out. The balance between COTS (commercial off the shelf) and custom software is difficult. Multiple customers, vendors, launch sites, and landing sites add to the complexity of efficient IT (Information Technology) tools.

Ingalls, John↗

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology↗

MSL Telecom Automated Anomaly Detection

The Mars Science Laboratory (MSL) Telecom Operations Team at the Jet Propulsion Laboratory (JPL) has implemented a machine learning system in order to automate the anomaly detection process as a part of daily operations. Machine learning enables reliable detection of anomalies in Telecom-related telemetry and automated reporting of Telecom subsystem status, resulting in an 90% reduction in team workload and improved anomaly detection reliability. At present, machine learning methods are used to detect: 1. Anomalous long-term trends in telemetry data 2. Anomalous time-domain evolution of telemetry values Both types of anomalies pose their own unique challenges that are addressed in different ways. In the first case, long term trending of daily minima, maximum, and mean telemetry values in temperatures, currents, voltages, and radio frequency (RF) power levels is used in addition to hard threshold safety checks to look for changes in long-term equipment health and performance. Long-term trending methods allow for ordinary seasonal variations in these quantities caused by temperature changes over the course of the Martian year while allowing operators to determine whether current performance remains in line with historical values from previous years. Changes in long-term trends can provide important insights into the health and status of the rover's on-board systems as well as valuable early warning if subtle degradation begins to take hold. But while trending of daily statistics is valuable, it does not detect anomalies in the short-term time evolution of data over the course of minutes or hours during a day, and this task is handled with short-term shape analysis. Principal components analysis (PCA) has been found to provide robust detection of short-term anomalies, and several examples of the use of PCA to detect actual anomalous events will be provided here. In using PCA, we use both the percentage of explained variance and also a log likelihood test on the PCA expansion coefficients to flag telemetry data for human review. Previous work in the field of spacecraft anomaly detection includes [1] for MSL and [2] for some other JPL missions.

Mukai, Ryan↗

Application of OpenFOAM to Plume Impingement in Space Environments

After 30 years of continuous human presence in low-earth orbit, NASA is returning to the moon and eventually will go to Mars. Travelling beyond low earth orbit requires NASA to learn how humans can live in Deep Space environments – beyond the protection of Earth’s magnetosphere and at distances from Earth that prevent a quick return in case of trouble. To this end, NASA is constructing the Lunar Gateway, an ISS-like space station to be put in orbit around the moon to act as a home base for Lunar exploration for NASA astronauts. The Gateway Lunar outpost will be built incrementally, via modules which will arrive at separate times and dock to the existing structure. The incremental addition of Gateway modules, and the docking of visiting vehicles, is achieved via a sequence of firings from the approaching body’s onboard reaction control system (RCS) thrusters to achieve the required approach trajectory. The typical hypergolic chemical RCS thrusters work by firing hot gases to produce adverse thrust and the needed change in velocity to safely finish the docking process. The exhaust gas from the RCS thrusters form plumes that expand into the vacuum of space and can impinge onto the outer surfaces of the Lunar Gateway, causing unwanted forces and moments, heat loads, sediment deposition, and in extreme cases, even surface erosion - all mechanisms that can damage the Lunar Gateway and must be minimized. Both permanent and visiting modules will have this RCS thruster exhaust impingement problem. This research aims to establish existing OpenFOAM solvers as a methodology for improving simulation techniques of rocket exhaust plume impingement in space environments. The flow structure of a plume in a space environment is complex; a plume that originates from a hypergolic chemical RCS thruster and expands into a vacuum will experience several regimes of rarefication. This range includes the continuum flow in the rocket nozzle through the fully rarefied free molecular flow further from the nozzle. The flow physics is different at these two extremes, and as such, the simulation approach for plumes is generally divided into a traditional computational fluid dynamics (CFD) simulation in and near the nozzle which is coupled to a subsequent direct simulation Monte Carlo (DSMC) simulation. At this time, the scope of this research is developing, verifying, and validating a method using existing solvers in the OpenFOAM framework for performing coupled CFD/DSMC calculations to determine the extent of plume impingement loading on generic space structures. This presentation will detail code-to-code comparisons between the hyStrath dsmcFoam+ solver, developed using OpenFOAM and available as open-source, and NASA’s in-house DSMC Analysis Code (DAC). Comparisons to several open-source publication findings using DAC [3,4] are presented, and advantages of using an OpenFOAM based solver are also discussed. The presentation concludes with a discussion of future work, and a plan for coupling the dsmcFoam+ solver with CFD simulations of chemical rocket engines for unified coupled plume simulation.

DSMC↗

Reviews and syntheses: Variable inundation across Earth's terrestrial ecosystems

Abstract. The structure, function, and dynamics of Earth's terrestrial ecosystems are profoundly influenced by how often (frequency) and how long (duration) they are inundated with water. A diverse array of natural and human-engineered systems experience temporally variable inundation whereby they fluctuate between inundated and non-inundated states. Variable inundation spans extreme events to predictable sub-daily cycles. Variably inundated ecosystems (VIEs) include hillslopes, non-perennial streams, wetlands, floodplains, temporary ponds, tidal systems, storm-impacted coastal zones, and human-engineered systems. VIEs are diverse in terms of inundation regimes, water chemistry and flow velocity, soil and sediment properties, vegetation, and many other properties. The spatial and temporal scales of variable inundation are vast, ranging from sub-meter to whole landscapes and from sub-hourly to multi-decadal. The broad range of system types and scales makes it challenging to predict the hydrology, biogeochemistry, ecology, and physical evolution of VIEs. Despite all experiencing the loss and gain of an overlying water column, VIEs are rarely considered together in conceptual, theoretical, modeling, or measurement frameworks and approaches. Studying VIEs together has the potential to generate mechanistic understanding that is transferable across a much broader range of environmental conditions, relative to knowledge generated by studying any one VIE type. We postulate that enhanced transferability will be important for predicting changes in VIE function in response to global change. Here we aim to catalyze cross-VIE science that studies drivers and impacts of variable inundation across Earth's VIEs. To this end, we complement expert mini-reviews of eight major VIE systems with overviews of VIE-relevant methods and challenges associated with scale. We conclude with perspectives on how cross-VIE science can derive transferable understanding via unifying conceptual models in which the impacts of variable inundation are studied across multi-dimensional environmental space.

54 ENVIRONMENTAL SCIENCES↗

Left ventricular function during lower body negative pressure

The response of the human left ventricle to lower body negative pressure (LBNP) and the relation between left ventricular function and hemodynamic response were investigated. Ventricular function curves relating stroke volume to end-diastolic volume were obtained in 12 normal men. Volume data were derived from echocardiographic measurements of left ventricular end-systolic and end-diastolic diameters at rest and during lower body negative pressure (LBNP) at minus 40 mm Hg. End-diastolic volume decreased by 19% and stroke volume by 22%. There were no significant changes in heart rate, arterial blood pressure, or end-systolic volume. Thus, moderate levels of LBNP significantly reduce preload and stroke volume without affecting contractile state. The absence of significant changes in heart rate and arterial blood pressure in the presence of a significant reduction in stroke volume is consistent with an increase in systemic peripheral resistance mediated by low-pressure baroreceptors.

Ahmad, M.↗

Growth Factors and Tension-Induced Skeletal Muscle Growth

The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we have performed experiments to determine whether mechanical stimulation of cultured avian muscle cells alters their response to anabolic steroids or glucocorticoids. In static cultures, testosterone had no effect on muscle cell growth, but 5alpha-dihydrotestosterone and the synthetic steroid stanozolol increased cell growth by up to 18% and 30%, respectively, after a three day exposure. We completed development of a new IBM-based mechanical cell stimulator system to provide greater flexibility in operating and monitoring our experiments. Our previous long term studies on myofiber growth were designed around a perfusion system of our own design. We have recently changed to performing these studies using a modified CELLCO cartridge bioreactor system Z since it has been certified as the ground-based model for the Shuttle's Space Tissue Loss (STL) F= Cell Culture Module. The current goals of this aspect of the project are three fold: 1) to design a Z cell culture system for studying avian skeletal myofiber atrophy on the Shuttle and Space Station; 0 2) to expand the use of bioreactors to cells which do not grow in either suspension or attached to the hollow fibers; and 3) to combine the bioreactor system with our computerized mechanical cell stimulator to have a better in vitro model to study tension/gravity/stretch regulation of skeletal muscle size. Preliminary studies also reported on involved : (1) how release of tension can induce rapid atrophy of tissues cultured avian skeletal muscle cells, and (2) a mechanism to transfer and maintain avian skeletal muscle organoids in modified cartridges in the Space Tissue Loss Module.

Vandenburgh, Herman H.↗

Cardiovascular Deconditioning in Humans: Human Studies Core

Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

Williams, Gordon↗

Crystal Growth Rate Dispersion: A Predictor of Crystal Quality in Microgravity?

In theory macromolecular crystals grow through a process involving at least two transport phenomena of solute to the crystal surface: diffusion and convection. In absence of standard gravitational forces, the ratio of these two phenomena can change and explain why crystal growth in microgravity is different from that on Earth. Experimental evidence clearly shows, however, that crystal growth of various systems is not equally sensitive to reduction in gravitational forces, leading to quality improvement in microgravity for some crystals but not for others. We hypothesize that the differences in final crystal quality are related to crystal growth rate dispersion. If growth rate dispersion exists on Earth, decreases in microgravity, and coincides with crystal quality improvements then this dispersion is a predictor for crystal quality improvement. In order to test this hypothesis, we will measure growth rate dispersion both in microgravity and on Earth and will correlate the data with previously established data on crystal quality differences for the two environments. We present here the first crystal growth rate measurement data for three proteins (lysozyme, xylose isomerase and human recombinant insulin), collected on Earth, using hardware identical to the hardware to be used in microgravity and show how these data correlate with crystal quality improvements established in microgravity.

Kephart, Richard D.↗