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Insulin secretion and sensitivity in space flight: diabetogenic effects

Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.

Review↗

Research on the adaptation of skeletal muscle to hypogravity Past and future directions

The results of previous research on the cellular effects of microgravity on rat tissue are reviewed and areas of future necessary research are identified. The rats were flown on board Cosmos 605, 782, and 936. Postflight tissue analyses revealed increases in connective tissue cells and focal disruption of muscle fibers due to the microgravity environment of space. Evidence has been found for muscular and neural changes occurring as a result of reentry stresses. It is suggested that a data base be established for quantizing muscle function with electromyography, measurements of force output, and length measurement. The data can serve as a reference for comparisons with data obtained in orbiting laboratories such as the Spacelab. The experiments will have a goal of defining and preventing the mechanism of neuromuscular atrophy.

Riley, D. A.↗

A facility for precise temperature control applications in microgravity

The general design, main components, and operation of the isothermal dendritic growth apparatus (IDGA) designed for microgravity experimentation are described. The four major subsystems of the IDGA are a temperature controlled thermostatic bath capable of milli-kelvin stability, a photographic data collection system, a crystal growth chamber, and a growth detection system to initiate data collection. Some of the specific experiments that could utilize the capabilities of the IDGA are dendritic growth in alloys, monotectic systems, life science experiments, and technological applications.

Glicksman, M. E.↗

The pituitary - Aging and spaceflown rats

Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

Hymer, W. C.↗

The solid surface combustion experiment aboard the USML-1 mission

AA Experimental results from the five experiments indicate that flame spread rate increases with increasing ambient oxygen content and pressure. An experiment was conducted aboard STS-50/USML-1 in the solid Surface Combustion Experiment (SSCE) hardware for flame spread over a thin cellulosic fuel in a quiescent oxidizer of 35% oxygen/65% nitrogen at 1.0 atm. pressure in microgravity. The USML-1 test was the fourth of five planned experiments for thin fuels, one performed during each of five Space Shuttle Orbiter flights. Data that were gathered include gas- and solid-phase temperatures and motion picture flame images. Observations of the flame are described and compared to theoretical predictions from steady and unsteady models that include flame radiation from CO2 and H2O. Experimental results from the five esperiments indicate that flame spread rate increases with increasing ambient oxygen content and pressure. The brightness of the flame and the visible soot radiation also increase with increasing spread rate. Steady-state numerical predictions of temperature and spread rate and flame structure trends compare well with experimental results near the flame's leading edge while gradual flame evolution is captured through the unsteady model.

Altenkirch, Robert A.↗

Space Station Biological Research Project

NASA Ames Research Center is responsible for the development of the Space Station Biological Research Project (SSBRP) which will support non-human life sciences research on the International Space Station Alpha (ISSA). The SSBRP is designed to support both basic research to understand the effect of altered gravity fields on biological systems and applied research to investigate the effects of space flight on biological systems. The SSBRP will provide the necessary habitats to support avian and reptile eggs, cells and tissues, plants and rodents. In addition a habitat to support aquatic specimens will be provided by our international partners. Habitats will be mounted in ISSA compatible racks at u-g and will also be mounted on a 2.5 m diameter centrifuge except for the egg incubator which has an internal centrifuge. The 2.5 m centrifuge will provide artificial gravity levels over the range of 0.01 G to 2 G. The current schedule is to launch the first rack in 1999, the Life Sciences glovebox and a second rack early in 2001, a 4 habitat 2.5 in centrifuge later the same year in its own module, and to upgrade the centrifuge to 8 habitats in 2004. The rodent habitats will be derived from the Advanced Animal Habitat currently under development for the Shuttle program and will be capable of housing either rats or mice individually or in groups (6 rats/group and at least 12 mice/group). The egg incubator will be an upgraded Avian Development Facility also developed for the Shuttle program through a Small Business and Innovative Research grant. The Space Tissue Loss cell culture apparatus, developed by Walter Reed Army Institute of Research, is being considered for the cell and tissue culture habitat. The Life Sciences Glovebox is crucial to all life sciences experiments for specimen manipulation and performance of science procedures. It will provide two levels of containment between the work volume and the crew through the use of seals and negative pressure. The glovebox will accommodate use by two crew persons simultaneously and the capability for real time video down-link and data acquisition. In house testbeds and Phase B studies of the centrifuge validated the concepts of vibration isolation and autobalancing systems to meet the ISSA microgravity requirements. The vibration isolation system is effective above the centrifuge rotation frequency while the autobalancing system on the rotor removes vibration at and below the rotation rate. Torque of the Station, induced by spin-up/spindown of the centrifuge, can be minimized by controlling spin-up/spin-down rates. The SSBRP and ISSA will provide the opportunity to perform long-term, repeatable and high quality science. The long duration increments available on the Station will permit multigeneration studies of both plants and animals which have not previously been possible. The u-g habitat racks and the eight habitat centrifuge will accommodate sufficient number of specimens to permit statistically significant sampling of specimens to investigate the time course of adaptation to altered gravity environments. The centrifuge will, for the first time, permit investigators to use gravity itself as a tool to investigate fundamental processes, to investigate the intensity and duration of gravity to maintain normal structure and function, to separate the effects of u-g from other environmental factors and to examine artificial gravity as a potential countermeasure for the physical deconditioning observed during space flight.

Johnson, Catherine C.↗

Loss of T cell precursors after spaceflight and exposure to vector-averaged gravity

Using fetal thymus organ culture (FTOC), we examined the effects of spaceflight and vector-averaged gravity on T cell development. Under both conditions, the development of T cells was significantly attenuated. Exposure to spaceflight for 16 days resulted in a loss of precursors for CD4+, CD8+, and CD4+CD8+ T cells in a rat/mouse xenogeneic co-culture. A significant decrease in the same precursor cells, as well as a decrease in CD4-CD8- T cell precursors, was also observed in a murine C57BL/6 FTOC after rotation in a clinostat to produce a vector-averaged microgravity-like environment. The block in T cell development appeared to occur between the pre-T cell and CD4+CD8+ T cell stage. These data indicate that gravity plays a decisive role in the development of T cells.

Flight Experiment↗

NASA Tech Briefs, November 2003

Topics covered include: Computer Program Recognizes Patterns in Time-Series Data; Program for User-Friendly Management of Input and Output Data Sets; Noncoherent Tracking of a Source of a Data-Modulated Signal; Software for Acquiring Image Data for PIV; Detecting Edges in Images by Use of Fuzzy Reasoning; A Timer for Synchronous Digital Systems; Prototype Parts of a Digital Beam-Forming Wide-Band Receiver; High-Voltage Droplet Dispenser; Network Extender for MIL-STD-1553 Bus; MMIC HEMT Power Amplifier for 140 to 170 GHz; Piezoelectric Diffraction-Based Optical Switches; Numerical Modeling of Nanoelectronic Devices; Organizing Diverse, Distributed Project Information; Eigensolver for a Sparse, Large Hermitian Matrix; Modified Polar-Format Software for Processing SAR Data; e-Stars Template Builder; Software for Acoustic Rendering; Functionally Graded Nanophase Beryllium/Carbon Composites; Thin Thermal-Insulation Blankets for Very High Temperatures; Prolonging Microgravity on Parabolic Airplane Flights; Device for Locking a Control Knob; Cable-Dispensing Cart; Foam Sensor Structures Would be Self-Deployable and Survive Hard Landings; Real-Gas Effects on Binary Mixing Layers; Earth-Space Link Attenuation Estimation via Ground Radar Kdp; Wedge Heat-Flux Indicators for Flash Thermography; Measuring Diffusion of Liquids by Common-Path Interferometry; Zero-Shear, Low-Disturbance Optical Delay Line; Whispering-Gallery Mode-Locked Lasers; Spatial Light Modulators as Optical Crossbar Switches; Update on EMD and Hilbert-Spectra Analysis of Time Series; Quad-Tree Visual-Calculus Analysis of Satellite Coverage; Dyakonov-Perel Effect on Spin Dephasing in n-Type GaAs; Update on Area Production in Mixing of Supercritical Fluids; and Quasi-Sun-Pointing of Spacecraft Using Radiation Pressure.

Source record↗

Estimated Muscle Loads During Squat Exercise in Microgravity Conditions

Loss of muscle mass in microgravity is one of the primary factors limiting long-term space flight. NASA researchers have developed a number of exercise devices to address this problem. The most recent is the Advanced Resistive Exercise Device (ARED), which is currently used by astronauts on the International Space Station (ISS) to emulate typical free-weight exercises in microgravity. ARED exercise on the ISS is intended to reproduce Earth-level muscle loads, but the actual muscle loads produced remain unknown as they cannot currently be measured directly. In this study we estimated muscle loads experienced during squat exercise on ARED in microgravity conditions representative of Mars, the moon, and the ISS. The estimates were generated using a subject-specific musculoskeletal computer model and ARED exercise data collected on Earth. The results provide insight into the capabilities and limitations of the ARED machine.

Fregly, Christopher D.↗

Expanded Benefits for Humanity from the International Space Station

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

Rai, Amelia↗

An Approach to Studying the Reliability of Microgravity Experiments

The identification of key factors that influence the nonsuccess of experiments conducted under microgravity conditions will aid in the planning, design, and implementation of future space shuttle experiments, as well as other microgravity experiments (i.e., experiments conducted on the space station). Similarly, knowledge of the experiments' reliability will assist in forecasting the success of forthcoming experiments. Since a relatively large number of space shuttle experiments have been conducted to date, a substantial pool of data exists for assessing the possible causes or factors which influence experiment nonsuccesses. This report details the task being undertaken at NASA Lewis Research Center (LeRC) to measure the space shuttle experiments' nonsuccess trends and identify causes that significantly affect their performance. It addresses the activities associated with correlating experiment macro-factors with experiment nonsuccesses. The development and implementation of a microgravity database to be used for tracking and correlating experiment nonsuccess factors, as well as the criteria for measuring experiment success and nonsuccess, are also discussed.

Thaggard, Michael↗

Assessing the Risk of Disc Heniation Related to Landing Impact Following Long-duration Spacecraft

Previous research has shown that crewmembers returning on the Space Shuttle have an increased incidence of herniated nucleus pulposus after spaceflight. This increased risk is thought to be related to disc volume expansion due to unloading and prolonged exposure to microgravity. Although there is an increased risk of disc herniation in Space Shuttle astronauts, it is unknown if dynamic landing loads further contribute to the risk of herniation. To determine if dynamic loads increase the risk of incidence, data from crewmembers (excluding cosmonauts) returning on the Soyuz spacecraft will be compared to Space Shuttle astronauts. These data will be obtained from the Lifetime Surveillance of Astronaut Health (LSAH) Project at NASA. Severity and incidence after spaceflight will be mined from the data, and statistical analyses will be used to determine if Soyuz crewmembers have a higher incidence of disc herniation than Space Shuttle crewmembers. The results are expected to show no difference between Space Shuttle and Soyuz crewmembers, indicating that higher dynamic loads on landing and long-duration spaceflight do not significantly increase the risk of disc herniation. If no difference is shown between the two crewmember populations, then disc volume expansion due to microgravity does not significantly increase the risk of injury due to dynamic loads for deconditioned crewmembers. Any risk associated with deconditioning would be primarily due to bone structure changes and resulting bone strength changes. This study is an important first step in determining whether the spinal disc plays a role in injury due to dynamic loads.

Somers, J. T.↗

Modeling of a Non-Dilute Alloy Solidification Under Terrestrial and Microgravity Conditions

A general finite element model of non-dilute alloy solidification was used to simulate growth of HgCdTe from the melt. 2-D and 3-D models with and without Oberbeck-Boussinesq (O-B) approximation were used. Verification of the 3-D model was based on experimental data. The location and the shape of the interface were determined using melting temperatures obtained from the HgCdTe liquidus curve. Double-diffusive convection in the melt is caused by radial temperature gradients and by rejection at the solid-melt interface of the heavier HgTe-rich solute. Because of these complicating factors, dimensional rather than non-dimensional modeling was performed. Models based on complete set of Navier-Stokes equations for compressible media are superior to the O-B approximation in microgravity, because they provide more accurate estimation of convection.

Bune, Andris V.↗

A Multi-Omics Approach Demonstrates that Spaceflight Leads to Lipid Accumulation in Mouse Livers

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. We analyzed liver transcriptomic and proteomic data from three mouse spaceflight experiments flown aboard the International Space Station (Rodent Research-1 NASA (RR-1 NASA), Rodent Research-1 CASIS (RR-1 CASIS), Rodent Research-3 (RR-3)), and one mouse experiment flown on the Space Shuttle (Commercial Biomedical Testing Module-3 (CBTM-3) aboard STS-135). Despite the differences in genetic background and time of exposure to microgravity it was shown through Oil Red staining and histology that increased lipid accumulation was occurring in the liver of all mice flown in space compared to the ground controls. This led to further pursue the existing GeneLab datasets related to liver omics data from these mice. We were able to discover key conserved pathways across all the mice independent of the flight conditions that were related to increased lipid metabolism, fatty acid metabolism, both lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions which include ESR1, GCG, and NR1I2 being inhibited and INS being activated. Interestingly, estrogen receptor alpha (ESR1) expression has been known to be heavily involved with lipoprotein metabolism. In addition, insulin (INS) is the primary driver for fat metabolism and increased INS has been associated with increased fatty acids in the liver. Through additional proteomic analysis we were able to identify the majority of the key proteins related to lipids for both the RR-1 and RR-3 rodents were being up-regulated in the livers when comparing flight to ground controls. This additional confirmation of the lipid associated activity also showed that the lipid related proteins are heavily involved with lipid metabolism, cholesterol binding, and cholesterol metabolism. Lastly, the analysis also revealed that the circadian clock related pathways in the liver are commonly being increased across all space flight conditions which has also been reported in the literature to potentially cause increased liver damage. The combination of the very strong lipid uptake in the liver and the transcriptomic/proteomic signatures (including the circadian clock pathways) following spaceflight are consistent with early onset of liver disease. Taken together, these data indicate that, activation of lipotoxic pathways could persist during longer duration spaceflight which might result in the development of liver disease

Lipids↗

Programmatic Considerations to Reduce the Risk of Adverse Renal Stone Events in Spaceflight

Introduction: Microgravity exposure may alter the likelihood that astronauts will experience renal stones. The potential risk includes both acute and chronic health issues, with the potential for significant impact on mission objectives. Methods: To understand the role of the NASA's Human Research Program (HRP) research agenda in both preventing and addressing renal stones in spaceflight, current astronaut epidemiologic data and a summary of programmatic considerations are reviewed. Results: Although there has never been a symptomatic renal stone event in a U.S. crewmember during spaceflight, urine chemistry has been altered - likely due to induced changes in renal physiology as a result of exposure to microgravity. This may predispose astronauts to stone formation, leading the HRP to conduct and sponsor research to: 1) understand the risk of stone formation in space; 2) prevent stones from forming; and 3) address stones that may form by providing novel diagnostic and therapeutic approaches. Discussion: The development of a renal stone during spaceflight is a significant medical concern that requires the HRP to minimize this risk by providing the ability to prevent, diagnose, monitor and treat the condition during spaceflight. A discussion of the risk as NASA understands it is followed by an overview of the multiple mitigations currently under study, including novel ultrasound techniques for stone detection and manipulation, and how they may function as part of a larger exploration medical system.

Antonsen, Erik↗

Diffusive and Radiative Transport in Fires (DARTFire): Opposed-Flow Flame Spread in Low-Velocity Flows

For flames spreading into a low-velocity flow that can only be obtained in microgravity, we have observed behavior that is different from that which is obtained at higher velocities where radiative effects are unimportant and species transport is relatively fast. Unfortunately, lack of a large body of low-gravity flame spread experimental data inhibits progress in developing an understanding of the physics of low-velocity, opposed-flow flame spread phenomena. Recent DARTFire sounding rocket experimental studies though, coupled with developing theory and modelling, have allowed some strides in understanding to be made, on which we report here. Four launches to date have resulted in six experiments for opposed-flow flame spread over a thick PMMA sample. During the 6 min microgravity period, the PMMA samples were ignited, and steady flame spread was studied under varied flow velocity, oxidizer atmospheric conditions, and, because radiative heat transfer is so important in these slowly spreading flames, external radiant flux. These were the first attempts at such experimental control and measurement in microgravity. A recent reflight of the Solid Surface Combustion Experiment (SSCE) has demonstrated, as modelling predicts, that for the thick fuel of the DARTFire experiment, flame spread in a quiescent environment is a transient process evolving from ignition to extinction on the order of 600 s (Altenkirch et al., 1999). Further study then of the effects of radiation in the very low-velocity opposing flows is of interest in understanding the transition from steady, sustained spread to the unsteady evolution to extinction as the opposing flow is reduced further and eventually removed.

Altenkirch, R. A.↗

Stability of Wavy Films in Gas-Liquid Two-Phase Flows at Normal and Microgravity Conditions

For flow rates of technological interest, most gas-liquid flows in pipes are in the annular flow regime, in which, the liquid moves along the pipe wall in a thin, wavy film and the gas flows in the core region. The waves appearing on the liquid film have a profound influence on the transfer rates, and hence on the design of these systems. We have recently proposed and analyzed two boundary layer models that describe the characteristics of laminar wavy films at high Reynolds numbers (300-1200). Comparison of model predictions to 1-g experimental data showed good agreement. The goal of our present work is to understand through a combined program of experimental and modeling studies the characteristics of wavy films in annular two-phase gas-liquid flows under normal as well as microgravity conditions in the developed and entry regions.

Balakotaiah, V.↗

Microgravity Science and Applications. Program Tasks and Bibliography for FY 1993

An annual report published by the Microgravity Science and Applications Division (MSAD) of NASA is presented. It represents a compilation of the Division's currently-funded ground, flight and Advanced Technology Development tasks. An overview and progress report for these tasks, including progress reports by principal investigators selected from the academic, industry and government communities, are provided. The document includes a listing of new bibliographic data provided by the principal investigators to reflect the dissemination of research data during FY 1993 via publications and presentations. The document also includes division research metrics and an index of the funded investigators. The document contains three sections and three appendices: Section 1 includes an introduction and metrics data, Section 2 is a compilation of the task reports in an order representative of its ground, flight or ATD status and the science discipline it represents, and Section 3 is the bibliography. The three appendices, in the order of presentation, are: Appendix A - a microgravity science acronym list, Appendix B - a list of guest investigators associated with a biotechnology task, and Appendix C - an index of the currently funded principal investigators.

Source record↗