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Effects of a 60-day confinement on the blood pressure, hormonal responses and body fluids of a mixed crew.

During the EXEMSI experiment, an international crew of 4 subjects (1 woman and 3 men) was confined for 60 days in a normobaric diving chamber (with 1060 mbar atmospheric pressure) to simulate life in a space station and to assess the effects of confinement on psychological and physiological factors. Blood pressure and blood volume regulating hormones (atrial natriuretic peptide, renin, aldosterone) and urine data (24-h urine outputs, ionogram) were measured before (BDC: baseline data collection), during (D: day) and after (R: recovery) confinement. We also measured energy expenditure and total body water, 14 days before, and after 27 days of confinement, by the double-labeled water method. We found a marked increase in 24-h urine output during most of the confinement in the men and the woman. Body weight (-1.8 +/- 0.9 kg) and energy expenditure (-1064 +/- 143 kcal/d, p<0.01) decreased in the 3 men. The total body water (TBW) decreased by 1.5 +/- 1.2 l in the men. Stress was not indicated by plasma and urine catecholamines but plasma growth hormone was elevated on D2 (p<0.01 vs. BDC) in the men. This study shows that confinement conditions can modify body fluid (increases in 24-h urine outputs and TBW changes) and energetic metabolisms.

Adaptation, Physiological↗

Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis in astronauts.

Reentry orthostasis secondary to a prolonged exposure to microgravity is a common problem among astronauts. However, the physiologic mechanisms are poorly understood due to the many control systems involved. In this study an advanced computer model of cardiovascular functioning was employed in a systems analysis approach to clarify the relative importance of some of the adaptive physiologic processes engaged when humans return from space. After simulation of the conditions of zero gravity for one month, the model predicted that the change in capacitance of the lower extremity veins resulting from a loss of external fluid forces in the dehydrated extracellular compartment was the dominant mechanism associated with reentry orthostasis. This condition appears accentuated in women due to their inherent lower center of gravity and proportionately larger mass in the lower extremities.

Adaptation, Physiological↗

Space Station gas-grain simulation facility: application to exobiology.

The Space Station provides an environment in which the forces required to suspend particles during an experiment can be reduced by as much as six orders of magnitude. This reduction in levitation force enables us to perform many new experiments in a variety of disciplines. We have grouped these experiments into two categories: 1) those involving an individual particle or the interaction between a few particles and 2) those involving clouds in particles. We consider only particle experiments at this stage because cloud experiments suffer from electrostatic interactions and levitation-forced coalescence therefore requiring considerably more space, mass and crew interaction. The displacement of a particle resulting from g-jitter for ballistic, Knudsen and Stokes flow regimes is considered in detail and the radiation, acoustic, electrostatic and electromagnetic levitation mechanisms to control this motion are reviewed. We have selected the simulation of organic haze production ion Titan as an example experiment for detailed study. The objective of this experiment is to simulate the photolysis of methane and the subsequent formation of the organic haze particles in the upper atmosphere of Titan.

Aerosols↗

New space warping method for the simulation of large-scale macromolecular conformational changes.

A space warping method, facilitating the modeling of large-scale conformational changes in mesoscopic systems, is presented. The method uses a set of "global (or collective) coordinates" that capture overall behavior, in conjunction with the set of atomic coordinates. Application of the space warping method to energy minimization is discussed. Several simulations where the method is used to determine the energy minimizing structures of simple central force systems are analyzed. Comparing the results and behavior of the space warping method to simulations involving atomic coordinates only, it is found that the space warping method scales better with system size and also finds lower minima when the potential energy surface has multiple minima. It is shown that the transformation of [Ala16]+ in vacuo from linear to globular is captured efficiently using the space warping method.

Biopolymers↗

Simulated-annealing real-space refinement as a tool in model building.

Methods have been developed that further automate the building of macromolecular structures into electron-density maps. The software supports molecular-dynamics real-space refinement of an atomic model to local regions of a map within the context of a popular molecular-modeling program, O [Jones et al. (1991), Acta Cryst. A47, 110-119]. It is implemented as a module to the CNS refinement package [Brünger et al. (1998), Acta Cryst. D54, 905-921], controlled by a graphical user interface and commands executed directly through the molecular-graphics package. The method is illustrated with examples of the building and rebuilding of protein and nucleic acid models in which laborious manual adjustments are avoided. The resulting models show improved convergence during subsequent reciprocal-space refinement. The novel feature of the RSRef2000 software is the combination of simulated-annealing optimization with local real-space refinement, allowing several local minima to be explored quickly and automatically within the context of interactive model building.

Arginine Kinase↗

Patient-specific bronchoscope simulation with pq-space-based 2D/3D registration.

OBJECTIVE: The use of patient-specific models for surgical simulation requires photorealistic rendering of 3D structure and surface properties. For bronchoscope simulation, this requires augmenting virtual bronchoscope views generated from 3D tomographic data with patient-specific bronchoscope videos. To facilitate matching of video images to the geometry extracted from 3D tomographic data, this paper presents a new pq-space-based 2D/3D registration method for camera pose estimation in bronchoscope tracking. METHODS: The proposed technique involves the extraction of surface normals for each pixel of the video images by using a linear local shape-from-shading algorithm derived from the unique camera/lighting constraints of the endoscopes. The resultant pq-vectors are then matched to those of the 3D model by differentiation of the z-buffer. A similarity measure based on angular deviations of the pq-vectors is used to provide a robust 2D/3D registration framework. Localization of tissue deformation is considered by assessing the temporal variation of the pq-vectors between subsequent frames. RESULTS: The accuracy of the proposed method was assessed by using an electromagnetic tracker and a specially constructed airway phantom. Preliminary in vivo validation of the proposed method was performed on a matched patient bronchoscope video sequence and 3D CT data. Comparison to existing intensity-based techniques was also made. CONCLUSION: The proposed method does not involve explicit feature extraction and is relatively immune to illumination changes. The temporal variation of the pq distribution also permits the identification of localized deformation, which offers an effective way of excluding such areas from the registration process.

Algorithms↗

[Applied psychoacoustics in space flight].

Simulation free field hearing by head phones by means of digital filter technics was used to investigate directional hearing and audiocinetic vection in microgravity. Our data showed basic informations for the understanding of the reciprocal influence of vestibular and auditory inputs for dynamic orientation. The technical equipment of free field hearing simulation by headphones and the performed experiments are described in detail. Furthermore the new established technology is discussed in terms of the value in psychoacoustic research as well as in clinical practice.

Auditory Perception↗

Altered cytokine expression in tissues of mice subjected to simulated microgravity.

Space flight is known to induce microgravity-associated immune dysfunction in humans, non-human primates and rodents. To understand the mechanism underlying these defects, several studies in rodents have been conducted in a ground-based antiorthostatic suspension (AOS) model that would mimic the effects of microgravity. In all these in vivo studies that showed the effects on cytokine profiles actually investigated the ex vivo production from culturing the cells isolated from whole organism that was exposed to space flight and/or microgravity. So, the purpose of the study was to examine the in vivo expression of cytokines in mice in immunologically important tissue environments of mice that were subjected to AOS. Cytokines such as Interleukin-1beta, (IL-1beta), IL-2, IL-3, IL-6, Interferon-gamma (IFN-gamma) and Tumor Necrosis Factor-alpha (TNF-alpha) were measured by Enzyme Linked Immunosorbent Assay (ELISA) in the homogenates of spleen tissue, lymph nodes and also in serum of AOS mice and compared with that of control mice. AOS induced no change in the IL-3 levels, but IL-1beta was increased significantly whereas IL-2 levels decreased in spleen, lymph nodes and serum. IL-6 levels did not differ in spleen but were significantly increased in lymph nodes and serum of AOS mice. IFN-gamma levels in spleen did not change but showed nonsignificant reduction in lymph nodes and significant reduction in serum in response to AOS. TNF-alpha levels in spleen and serum were unchanged and increased in lymph nodes. This in vivo cytokine study confirms the earlier findings that microgravity-simulated conditions induce tissue-specific immune response.

Animals↗

Effect of hydrodynamic flow on low-field spin-lattice relaxation in liquids in the nanoscopic vicinity of solid surfaces: theory and Monte Carlo simulations of model pore spaces.

It is shown that slow hydrodynamic flow with velocities of a few millimeters per second reduces the spin-lattice relaxation rate of fluids confined to pores of a diamagnetic, polar, solid material. The effect is predicted by an analytical theory and Monte Carlo simulations of model pore spaces. Adsorbate molecules diffusing in the vicinity of pore surfaces can perform adsorption, desorption, and readsorption cycles, effectively leading to displacements along the surface (also termed "bulk mediated surface diffusion" or BMSD). Since the surface determines the orientation of the adsorbed molecule relative to the external magnetic field, desorption at one site and readsorption at another site of a nonplanar surface will cause molecular reorientation. This is the basis of the "reorientation mediated by translational displacements" (RMTD) relaxation mechanism. If hydrodynamic flow is superimposed on diffusion, the RMTD process will be accelerated in a sort of rotational analog to translational hydrodynamic (or Taylor-Aris) dispersion. This reveals itself by a prolongation of spin-lattice relaxation times at low frequencies. The flow-relaxation effect takes place in the vicinity of the pore surfaces on the order of nanometers. The conclusions are (i) the BMSD and RMTD relaxation mechanism of fluids in porous materials is corroborated, (ii) hydrodynamic dispersion affects molecular displacements at surfaces, and (iii) interfacial slip in the sense of a molecular hopping, i.e., a desorption-readsorption process takes place.

Journal Article↗

Knotting of random ring polymers in confined spaces.

Stochastic simulations are used to characterize the knotting distributions of random ring polymers confined in spheres of various radii. The approach is based on the use of multiple Markov chains and reweighting techniques, combined with effective strategies for simplifying the geometrical complexity of ring conformations without altering their knot type. By these means we extend previous studies and characterize in detail how the probability to form a given prime or composite knot behaves in terms of the number of ring segments N and confining radius R. For 50 < or =N < or =450 we show that the probability of forming a composite knot rises significantly with the confinement, while the occurrence probability of prime knots are, in general, nonmonotonic functions of 1R. The dependence of other geometrical indicators, such as writhe and chirality, in terms of R and N is also characterized. It is found that the writhe distribution broadens as the confining sphere narrows.

Computer Simulation↗

The first European simulation of a long-duration manned space mission.

Europe's space flight ambitions will involve long-duration manned space missions in the next century. This objective has given rise to several studies being undertaken in "space-analogous" environments during the last few years. The first wholly space-oriented manned simulation study undertaken in Europe took place during 1990. It involved a crew of six isolated for 4 weeks in a hyperbaric chamber complex. The resources available for the study were primarily devoted to obtaining scientific data on the psychological and physiological effects of long-duration isolation and confinement on crew performance. Fundamental lessons were also learned on the operational side, and these will be fully exploited in setting up future simulation campaigns.

Humans↗

Foraminal pressure changes during intervertebral distraction simulating anterior cervical discectomy.

Distraction of the disc space over baseline height has been shown to increase foraminal size. The purpose of this procedure is to determine pressure changes, with disc space distraction simulating an anterior cervical discectomy and fusion (ACDF). An analysis of pressure changes during disc space distraction at C5-C6 was performed. Data were analyzed for maximal pressure observed and for pressure change with prolonged distraction. Five cadaveric specimens underwent a discectomy at the C5-C6 level. Distraction of the disc space was performed and pressure measurements were obtained from within the foramen. Measurements were made for maximal pressure with an intact posterior longitudinal ligament (PLL), divided PLL, and with the nerve root removed from within the foramen. Pressures were also recorded with prolonged distraction until a steady state was achieved. Incremental distraction of +2, +4, and +6 mm resulted in pressure increases within the foramen. Sectioning of the PLL did not affect these increases. Removal of the nerve root from the foramen resulted in pressure increases; however, these were not significantly different from baseline. Prolonged distraction produced an initial increase and a gradual return toward baseline. Final pressures still differed significantly from baseline. Increase intraforaminal pressures can be seen with increasing disc space distraction such as occurs during an ACDF. This suggests that either the foramen narrows in at least one dimension and/or soft-tissue attachments to the nerve produce a tensile force in the nerve as they tighten. The pressure increases relax over time.

Aged↗

Biological space experiments for the simulation of Martian conditions: UV radiation and Martian soil analogues.

The survivability of resistant terrestrial microbes, bacterial spores of Bacillus subtilis, was investigated in the BIOPAN facility of the European Space Agency onboard of Russian Earth-orbiting FOTON satellites (BIOPAN I -III missions). The spores were exposed to different subsets of the extreme environmental parameters in space (vacuum, extraterrestrial solar UV, shielding by protecting materials like artificial meteorites). The results of the three space experiments confirmed the deleterious effects of extraterrestrial solar UV radiation which, in contrast to the UV radiation reaching the surface of the Earth, also contains the very energy-rich, short wavelength UVB and UVC radiation. Thin layers of clay, rock or meteorite material were shown to be only successful in UV-shielding, if they are in direct contact with the spores. On Mars the UV radiation climate is similar to that of the early Earth before the development of a protective ozone layer in the atmosphere by the appearance of the first aerobic photosynthetic bacteria. The interference of Martian soil components and the intense and nearly unfiltered Martian solar UV radiation with spores of B. subtilis will be tested with a new BIOPAN experiment, MARSTOX. Different types of Mars soil analogues will be used to determine on one hand their potential toxicity alone or in combination with solar UV (phototoxicity) and on the other hand their UV protection capability. Two sets of samples will be placed under different cut-off filters used to simulate the UV radiation climate of Mars and Earth. After exposure in space the survival of and mutation induction in the spores will be analyzed at the DLR, together with parallel samples from the corresponding ground control experiment performed in the laboratory. This experiment will provide new insights into the principal limits of life and its adaptation to environmental extremes on Earth or other planets which and will also have implications for the potential for the evolution and distribution of life.

Bacillus subtilis↗

Congruent qualitative behavior of complete and reconstructed phase space trajectories from biomolecular dynamics simulation.

Central to the study of a complex dynamical system is knowledge of its phase space behavior. Experimentally, it is rarely possible to record a system's (multidimensional) phase space variables. Rather, the system is observed via one (or few) scalar-valued signal(s) of emission or response. In dynamical systems analysis, the multidimensional phase space of a system can be reconstructed by manipulation of a one-dimensional signal. The trick is in the construction of a (higher-dimensional) space through the use of a time lag (or delay) on the signal time series. The trajectory in this embedding space can then be examined using phase portraits generated in selected subspaces. By contrast, in computer simulation, one has an embarrassment of riches: direct access to the complete multidimensional phase space variables, at arbitrary time resolution and precision. Here, the problem is one of reducing the dimensionality to make analysis tractable. This can be achieved through linear or nonlinear projection of the trajectory into subspaces containing high information content. This study considers trajectories of the small protein crambin from molecular dynamics simulations. The phase space behavior is examined using principal component analysis on the Cartesian coordinate covariance matrix of 138 dimensions. In addition, the phase space is reconstructed from a one dimensional signal, representing the radius of gyration of the structure along the trajectory. Comparison of low-dimensional phase portraits obtained from the two methods shows that the complete phase space distribution is well represented by the reconstruction. The study suggests that it may be possible to develop a deeper connection between the experimental and simulated dynamics of biomolecules via phase space reconstruction using data emerging from recent advances in single-molecule time-resolved biophysical techniques.

Animals↗

Determination of three-dimensional structures of proteins from interproton distance data by hybrid distance geometry-dynamical simulated annealing calculations.

A new hybrid distance space-real space method for determining three-dimensional structures of proteins on the basis of interproton distance restraints is presented. It involves the following steps: (i) the approximate polypeptide fold is obtained by generating a set of substructures comprising only a small subset of atoms by projection from multi-dimensional distance space into three-dimensional cartesian coordinate space using a procedure known as 'embedding'; (ii) all remaining atoms are then added by best fitting extended amino acids one residue at a time to the substructures; (iii) the resulting structures are used as the starting point for real space dynamical simulated annealing calculations. The latter involve heating the system to a high temperature followed by slow cooling in order to overcome potential barriers along the pathway towards the global minimum region. This is carried out by solving Newton's equations of motion. Unlike conventional restrained molecular dynamics, however, the non-bonded interactions are represented by a simple van der Waals repulsion term. The method is illustrated by calculations on crambin (46 residues) and the globular domain of histone H5 (79 residues). It is shown that the hybrid method is more efficient computationally and samples a larger region of conformational space consistent with the experimental data than full metric matrix distance geometry calculations alone, particularly for large systems.

Histones↗

The effect of simulated microgravity on bacteria from the Mir space station.

The effects of simulated microgravity on two bacterial isolates, Sphingobacterium thalpophilium and Ralstonia pickettii (formerly Burkholderia pickettii), originally recovered from water systems aboard the Mir space station were examined. These bacteria were inoculated into water, high and low concentrations of nutrient broth and subjected to simulated microgravity conditions. S. thalpophilium (which was motile and had flagella) showed no significant differences between simulated microgravity and the normal gravity control regardless of the method of enumeration and medium. In contrast, for R. pickettii (that was non-motile and lacked flagella), there were significantly higher numbers in high nutrient broth under simulated microgravity compared to normal gravity. Conversely, when R. pikkettii was inoculated into water (i.e., starvation conditions) significantly lower numbers were found under simulated microgravity compared to normal gravity. Responses to microgravity depended on the strain used (e.g., the motile strain exhibited no response to microgravity, while the non-motile strain did), the method of enumeration, and the nutrient concentration of the medium. Under oligotrophic conditions, non-motile cells may remain in geostationary orbit and deplete nutrients in their vicinity, while in high nutrient medium, resources surrounding the cell may be sufficient so that high growth is observed until nutrients becoming limiting.

Bacterial Physiological Phenomena↗

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

Adrenergic alpha-Agonists↗