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Decompression sickness during simulated extravehicular activity: ambulation vs. non-ambulation.

BACKGROUND: Extravehicular activity (EVA) is required from the International Space Station on a regular basis. Because of the weightless environment during EVA, physical activity is performed using mostly upper-body movements since the lower body is anchored for stability. The adynamic model (restricted lower-body activity; non-ambulation) was designed to simulate this environment during earthbound studies of decompression sickness (DCS) risk. DCS symptoms during ambulatory (walking) and non-ambulatory high altitude exposure activity were compared. The objective was to determine if symptom incidences during ambulatory and non-ambulatory exposures are comparable and provide analogous estimates of risk under otherwise identical conditions. METHODS: A retrospective analysis was accomplished on DCS symptoms from 2010 ambulatory and 330 non-ambulatory exposures. RESULTS: There was no significant difference between the overall incidence of DCS or joint-pain DCS in the ambulatory (49% and 40%) vs. the non-ambulatory exposures (53% and 36%; p > 0.1). DCS involving joint pain only in the lower body was higher during ambulatory exposures (28%) than non-ambulatory exposures (18%; p < 0.01). Non-ambulatory exposures terminated more frequently with non-joint-pain DCS (17%) or upper-body-only joint pain (18%) as compared with ambulatory exposures, 9% and 11% (p < 0.01), respectively. DISCUSSION: These findings show that lower-body, weight-bearing activity shifts the incidence of joint-pain DCS from the upper body to the lower body without altering the total incidence of DCS or joint-pain DCS. CONCLUSIONS: Use of data from previous and future subject exposures involving ambulatory activity while decompressed appears to be a valid analogue of non-ambulatory activity in determining DCS risk during simulated EVA studies.

Decompression Sickness↗

Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution.

A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational 'leaps' to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.

Alanine↗

Simulation of launch and re-entry acceleration profiles for testing of shuttle and unmanned microgravity research payloads.

Microgravity experiments designed for execution in Get-Away Special canisters, Hitchhiker modules, and Reusable Re-entry Satellites will be subjected to launch and re-entry accelerations. Crew-dependent provisions for preventing acceleration damage to equipment or products will not be available for these payloads during flight; therefore, the effects of launch and re-entry accelerations on all aspects of such payloads must be evaluated prior to flight. A procedure was developed for conveniently simulating the launch and re-entry acceleration profiles of the Space Shuttle (3.3 and 1.7 x g maximum, respectively) and of two versions of NASA's proposed materials research Re-usable Re-entry Satellite (8 x g maximum in one case and 4 x g in the other). By using the 7 m centrifuge of the Gravitational Plant Physiology Laboratory in Philadelphia it was found possible to simulate the time dependence of these 5 different acceleration episodes for payload masses up to 59 kg. A commercial low-cost payload device, the "Materials Dispersion Apparatus" of Instrumentation Technology Associates was tested for (1) integrity of mechanical function, (2) retention of fluid in its compartments, and (3) integrity of products under simulated re-entry g-loads. In particular, the sharp rise from 1 g to maximum g-loading that occurs during re-entry in various unmanned vehicles was successfully simulated, conditions were established for reliable functioning of the MDA, and crystals of 5 proteins suspended in compartments filled with mother liquor were subjected to this acceleration load.

Acceleration↗

A comparison of methods for calculating NMR cross-relaxation rates (NOESY and ROESY intensities) in small peptides.

Three methods for calculating nuclear magnetic resonance cross-relaxation rates from molecular dynamics simulations of small flexible molecules have been compared in terms of their ability to reproduce relaxation data obtained experimentally and to produce consistent descriptions of the system. The importance of the accuracy of the simulation versus the amount of sampling of phase space has also been assessed by comparing different length simulations performed with different time step schemes. A nine-residue peptide from the protein HPr of E. coli was used as a test system. The work shows that, in this case, single conformations or a limited ensemble of configurations are insufficient to properly describe the behavior of the peptide and that different approaches to incorporate molecular motions lead to significant differences in the cross-relaxation rates calculated. The correlation between the cross-relaxation rates calculated from simulations performed with different time step schemes was high and increased with increasing simulation length indicating that the extent of sampling is more important than the details of the atomic motion.

Bacterial Proteins↗

Inhibited interferon production after space flight.

Several studies have been performed in our laboratories indicating that interferon production may be impaired in rodents after space flight. Using an antiorthostatic suspension model that simulates some of the effects of microgravity seen during space flight, we have shown that interferon-alpha/beta production was inhibited. The inhibition was not due solely to the stress of suspension. The inhibited interferon production was transient, as suspended animals returned to normal caging recovered the ability to produce interferon. Antiorthostatic suspension of mice also resulted in a loss of resistance to infection with the diabetogenic strain of encephalomyocarditis virus, which correlated with the drop in interferon production. In rats flown in US Space Shuttle mission SL-3, interferon-gamma production was inhibited severely when spleen cells were challenged with concanavalin-A upon return to earth. In contrast, interleukin-3 production by these cells was normal. These results suggest that immune responses may be altered after antiorthostatic modeling or space flight, and the resistance to viral infections may be especially affected.

Animals↗

The effect of intervertebral disc space narrowing on the contact force between the nerve root and a simulated disc protrusion.

An instrumented probe mounted on the anterior surface of the lumbar spine over an excised lumbar intervertebral disc was used to stimulate a disc protrusion in 12 fresh cadavers. The contact force between probe and nerve root was measured as a function of two independent variables: probe protrusion depth and disc space height. The contact force on the nerve root was found to increase with increasing probe depth. Disc space widening increased the contact force while narrowing the disc space decreased it. A simple mechanical model analysis confirmed that the force exerted on the nerve root by the probe is the result of tension produced in the nerve root as it is deformed by the probe. The mechanical principle that disc narrowing can reduce the pressure on a nerve root produced by a disc protrusion may be an explanation of how chemonycleolysis relieves sciatic pain.

Adolescent↗

The microgravity environment for experiments on the International Space Station.

Experiments are sent to space laboratories in order to take advantage of the low-gravity environment. However, it is crucial to appreciate the distinction between the real microgravity environment and "weightlessness" or "simulated microgravity". The microgravity in space laboratories may be of much smaller magnitude than the gravitational acceleration on earth. However, it is not zero, nor even one microg (defined as 1e-6 earth gravity). Moreover, the orientation is not uniaxial, as on earth. The net acceleration that acts on a space experiment arises from, e.g., orbital mechanics, atmospheric drag, and thruster firings, and it can act on the experiments in gravity-like ways. In essence, a well-defined, stable 1 g acceleration on the earth's surface is substituted for a complex array of dynamically changing accelerations with ever-changing frequency content, magnitude and direction. This paper will show measured accelerations on the Shuttle from launch to orbit, as well as the latest measurements on the International Space Station (ISS). The ISS data presented here represent over 34,790 hours of data obtained from June 2002 to April 2003 during Increments 5 and 6 of the ISS construction cycle. The quasisteady acceleration level on the ISS has been measured to be on the order of a few microg during time allotted to microgravity mode. The vibratory acceleration environment spans a rich spectrum from 0.01-300 Hz.

Acceleration↗

4D Monte Carlo simulation of proton beam scanning: modelling of variations in time and space to study the interplay between scanning pattern and time-dependent patient geometry.

When dosimetric effects in time-dependent geometries are studied, usually either the results of individual three-dimensional (3D) calculations are combined or probability-based approaches are applied. These methods may become cumbersome and time-consuming if high time resolution is required or if the geometry is complex. Furthermore, it is difficult to study double-dynamic systems, e.g., to investigate the influence of time-dependent beam delivery (i.e., magnetically moving beam spots in proton beam scanning) on the dose deposition in a moving target. We recently introduced the technique of 4D Monte Carlo dose calculation to model continuously changing geometries. In intensity modulated proton therapy, dose is delivered by individual pristine Bragg curves. Dose spots are positioned in the patient by varying magnetic field and beam energy. If the movement of these dose spots occurs during significant respiratory motion, interplay effects can take place. Because of the inhomogeneity of individual subfields, the consequences of motion can be more severe than in conventional proton therapy. We demonstrate how the technique of 4D Monte Carlo can be used to study interplay effects in proton beam scanning. Time-dependent beam delivery to a changing patient geometry is simulated in a single 4D dose calculation. Interplay effects between respiratory motion and beam scanning speed are demonstrated.

Dose-Response Relationship, Radiation↗

Solitary phase-space holes in pair plasmas.

We present theoretical and computer simulation studies of the formation and dynamics of solitary phase-space holes in pair plasmas, which can be applied to both electron-positron plasmas and to plasmas containing positively and negatively charged macro-ions or macro-particulates (charged dust grains). We apply our numerical treatment to the parameters used in a recent series of experiments in a pair ion plasma whose constituents are negatively and positively charged fullerene carbon nanotubes. New experiments should be conducted to confirm our theoretical and numerical predictions.

Journal Article↗

Phase-space invariants as indicators of the critical behavior of nanoaggregates.

A phase-space approach is proposed for molecular dynamics simulations, which serve as a bridge between detailed descriptions of microscopic world and macroscopic properties of matter. The introduction-aside from the angular momentum of spatial rotations-of other "hyperangular" momenta (the overall grand angular momentum of a cluster of particles and those describing the deformation and rearrangement modes) permits one to analyze different degrees of freedom and to extract, from simulation data, a kinetic energy partition in terms of phase-space invariants. Model calculations illustrate how these provide specific signatures of critical behavior, such as energy thresholds for openings of chaotic pathways in small clusters and for phase transitions in nanoaggregates.

Journal Article↗

Microgravity effects on water flow and distribution in unsaturated porous media: analyses of flight experiments.

Plants grown in porous media are part of a bioregenerative life support system designed for long-duration space missions. Reduced gravity conditions of orbiting spacecraft (microgravity) alter several aspects of liquid flow and distribution within partially saturated porous media. The objectives of this study were to evaluate the suitability of conventional capillary flow theory in simulating water distribution in porous media measured in a microgravity environment. Data from experiments aboard the Russian space station Mir and a U.S. space shuttle were simulated by elimination of the gravitational term from the Richards equation. Qualitative comparisons with media hydraulic parameters measured on Earth suggest narrower pore size distributions and inactive or nonparticipating large pores in microgravity. Evidence of accentuated hysteresis, altered soil-water characteristic, and reduced unsaturated hydraulic conductivity from microgravity simulations may be attributable to a number of proposed secondary mechanisms. These are likely spawned by enhanced and modified paths of interfacial flows and an altered force ratio of capillary to body forces in microgravity.

Capillary Action↗

Anisotropy, fiber curvature, and bath loading effects on activation in thin and thick cardiac tissue preparations: simulations in a three-dimensional bidomain model.

INTRODUCTION: A modeling study is presented to explore the effects of tissue conductivity, fiber orientation, and presence of an adjoining extracellular volume conductor on electrical conduction in cardiac muscle. Simulated results are compared with those of classical in vitro experiments on superfused thin layer preparations and on whole hearts. METHODS AND RESULTS: The tissue is modeled as a three-dimensional bidomain block adjoining an isotropic bath. In the thin layer model, the fibers are assumed parallel. In the thick block model, fiber rotation, curvature, and tipping are incorporated. Results from the thin layer model explain experimental observations that the rate of rise of the entire action potential upstroke is faster and the magnitude of the extracellular potential is smaller across fibers than along fibers in a uniformly propagating front. The simulation identified that this behavior only arises in tissue with unequal anisotropy in the two spaces and adjoining an extracellular bath. Simulated conduction and potential distributions in the thick block model are shown to well approximate experimental maps. The potentials are sensitive to changes in the fiber orientations. A slight 5 degrees tipping of intramural fibers out of the planes parallel to the epicardium and endocardium will lead to an asymmetry of the magnitudes of the positive regions. In addition, the introduction of fiber curvature leads to more realistic isochrone and extracellular potential distributions. The orientation of the central negative region of the extracellular potential is shown to be determined by the average of the fiber direction at the plane of pacing and the plane of recording. CONCLUSIONS: The simulations demonstrate the sensitivity of spread of activation and potential time courses and distributions to the underlying electrical properties in both thick and thin slabs. The bidomain model is shown to be a useful representation of cardiac tissue for interpreting experimental data of activation.

Action Potentials↗

Ternary diffusion and effective diffusion coefficients in alveolar spaces.

An experimentally verified mathematical model of non-equimolar ternary gas diffusion is applied to simulate the conditions existing in the alveolar spaces. When a fictitious gas film is erected a certain distance away from the alveolar membrane, and when the compositions at the two boundaries of the film are, respectively, the alveolar gas composition and a proportional mixture of inspired gas with the alveolar gas, the resulting fluxes of O2 and CO2 are essentially linearly related to their respective partial pressure gradients. From the slopes of these flux lines, effective diffusion coefficients are obtained. Ramifications of the effective diffusion coefficients approach are discussed.

Animals↗

Macromolecular crystallization in microgravity generated by a superconducting magnet.

About 30% of the protein crystals grown in space yield better X-ray diffraction data than the best crystals grown on the earth. The microgravity environments provided by the application of an upward magnetic force constitute excellent candidates for simulating the microgravity conditions in space. Here, we describe a method to control effective gravity and formation of protein crystals in various levels of effective gravity. Since 2002, the stable and long-time durable microgravity generated by a convenient type of superconducting magnet has been available for protein crystal growth. For the first time, protein crystals, orthorhombic lysozyme, were grown at microgravity on the earth, and it was proved that this microgravity improved the crystal quality effectively and reproducibly. The present method always accompanies a strong magnetic field, and the magnetic field itself seems to improve crystal quality. Microgravity is not always effective for improving crystal quality. When we applied this microgravity to the formation of cubic porcine insulin and tetragonal lysozyme crystals, we observed no dependence of effective gravity on crystal quality. Thus, this kind of test will be useful for selecting promising proteins prior to the space experiments. Finally, the microgravity generated by the magnet is compared with that in space, considering the cost, the quality of microgravity, experimental convenience, etc., and the future use of this microgravity for macromolecular crystal growth is discussed.

Animals↗

Contribution of airway resistance to airway pressure during mechanical ventilation: an experimental study.

Although airway resistance (R) is an important parameter of the pulmonary condition, its determination during mechanical ventilation is not easy. Most physicians estimate R from peak airway pressure during mechanical ventilation. We assessed the relationship between R and peak airway pressure by a computer simulation. The time course of airway pressure (Ptr) during mechanical ventilation was calculated from the airway pressure at end-inspiration and respiratory flow, allowing for the buffering effect of the dead space. The parameters for computer simulation were obtained from 5 paralyzed and mechanically ventilated dogs. The predicted Ptr curve was a function of airway resistance. Since R was not directly determined by the animal experiments, we determined R by using the Ptr curve most closely approximating the original Ptr curve as the true R. The R-peak tracheal pressure relationship predicted by computer simulation showed that the peak airway pressure increased almost linearly with increases in R. However, in computer simulation, when R was increased 10-fold from the value at airway relaxation, the peak airway pressure increased only 6-fold from the corresponding value. We conclude that peak airway pressure is a relatively insensitive parameter for the estimation of airway constriction during mechanical ventilation.

Airway Resistance↗

Planetary protection considerations for MarsNet and Mars sample return missions.

The ESA MarsNet mission proposal consists most probably of a trio of Mars landers. These landers each contain a variety of scientific equipment. The network of stations demands for a definition of its planetary protection requirements. With respect to the MarsNet mission only forward contamination problems will be considered. Future involvement of European efforts in planetary exploration including sample returns will also raise the problem of back contamination. A tradeoff study for the overall scientific benefit with respect to the approximative cost is necessary. Planetary protection guide-lines will be proposed by an interdisciplinary and international board of experts working in the fields of both biology and planetary science. These guide-lines will have to be flexible in order to be modified with respect to new research results, e.g. on adaptation of microorganisms to extreme (space) conditions. Experiments on the survival of microorganisms at conditions of simulated Mars surface and subsurface will have to be conducted in order to obtain a baseline data collection as a reference standard for future guide-lines.

Containment of Biohazards↗

Changes of pulmonary function in humans during exposure to +Gx acceleration after simulated and real microgravity.

An important goal of space medicine is preserving high tolerance and performance of cosmonauts an ring exposure to acceleration at the final flight stage given varying mission duration. Among physiological mechanisms limiting +Gx acceleration tolerance, an important role is played by disturbances of external respiration resulting from alterations of respiratory biomechanics, pulmonary gas exchange conditions, and arterial hypoxemia. However, at present data on external respiration changes during exposure to +Gx acceleration after simulated and real microgravity of varying duration, are extremely scanty.

Bed Rest↗

Electrical coupling and impulse propagation in anatomically modeled ventricular tissue.

Computer simulations were used to study the role of resistive couplings on flat-wave action potential propagation through a thin sheet of ventricular tissue. Unlike simulations using continuous or periodic structures, this unique electrical model includes random size cells with random spaced longitudinal and lateral connections to simulate the physiologic structure of the tissue. The resolution of the electrical model is ten microns, thus providing a simulated view at the subcellular level. Flat-wave longitudinal propagation was evaluated with an electrical circuit of over 140,000 circuit elements, modeling a 0.25 mm by 5.0 mm sheet of tissue. An electrical circuit of over 84,000 circuit elements, modeling a 0.5 mm by 1.5 mm sheet was used to study flat-wave transverse propagation. Under normal cellular coupling conditions, at the macrostructure level, electrical conduction through the simulated sheets appeared continuous and directional differences in conduction velocity, action potential amplitude and Vmax were observed. However, at the subcellular level (10 microns) unequal action potential delays were measured at the longitudinal and lateral gap junctions and irregular wave-shapes were observed in the propagating signal. Furthermore, when the modeled tissue was homogeneously uncoupled at the gap junctions conduction velocities decreased as the action potential delay between modeled cells increased. The variability in the measured action potential was most significant in areas with fewer lateral gap junctions, i.e., lateral gap junctions between fibers were separated by a distance of 100 microns or more.

Action Potentials↗