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[The monitoring of gas bubbles with a pulsed Doppler ultrasonic locator in humans working in a space suit].

Presented are results of gas bubbles monitoring in decompressed humans with the use of an ultrasonic pulse-Doppler locator (PDL). Unlike the classic Doppler bubbles detectors with continuous US emission, PDL is adjusted for reception of echo from a chosen volume of the right ventricle cavity; thus, the clutter due to cardiac beats and human locomotion is successfully rejected. During simulation of Russian EVAs, venous gas bubbles were detected in 3 out of 5 experiments with test-subjects clothed in everyday wear and in 2 out of 3 experiments with suited test-subjects.

Adult↗

Simulating the 'other-race' effect with autoassociative neural networks: further evidence in favor of the face-space model.

Other-race (OR) faces are less accurately recognized than same-race (SR) faces, but faster classified by race. This phenomenon has often been reported as the 'other-race' effect (ORE). Valentine (1991 Quarterly Journal of Experimental Psychology A: Human Experimental Psychology 43 161-204) proposed a theoretical multidimensional face-space model that explained both of these results, in terms of variations in exemplar density between races. According to this model, SR faces are more widely distributed across the dimensions of the space than OR faces. However, this model does not quantify nor state the dimensions coded within this face space. The aim of the present study was to test the face-space explanation of the ORE with neural network simulations by quantifying its dimensions. We found the predicted density properties of Valentine's framework in the face-projection spaces of the autoassociative memories. This was supported by an interaction for exemplar density between the race of the learned face set and the race of the faces. In addition, the elaborated face representations showed optimal responses for SR but not for OR faces within SR face spaces when explored at the individual level, as gender errors occurred significantly more often in OR than in SR face-space representations. Altogether, our results add further evidence in favor of a statistical exemplar density explanation of the ORE as suggested by Valentine, and question the plausibility of such coding for faces in the framework of recent neuroimaging studies.

Asian People↗

Staying in bed to benefit ESA's astronauts and Europe's citizens.

Since Yuri Gagarin's historic first flight into space in April 1961, it has quickly become evident that the space environment influences the human body in many different ways and causes it to adapt in ways that can lead to problems when returning to Earth's gravity. Much research has been performed in the meantime and our understanding of what happens to our bodies in space improved considerably during the Mir space station and Space Shuttle/Spacelab era. However, many questions, particularly regarding how to counteract those changes that we now know take place, still need to be addressed through studies on the International Space Station (ISS) and through simulations on the ground. As we enter an era in which crews will spend longer periods in space on the ISS and of longer term plans by almost every space-faring nation for missions to Mars, it is clear that much more knowledge is needed, and quickly. Although a few hundred men and women have already travelled into space, the operating environment severely limits the amount of systematic research that can be performed--a situation that is unlikely to change. Other avenues for addressing specific scientific questions in a controlled research environment must therefore be found. One of these complementary alternatives is head-down-tilt bed-rest studies in which volunteers are confined to beds that are tilted -6 deg below the horizontal at the head end. Every activity, including eating, reading, showering, etc., is performed in this position for the duration of the study. This leads to changes in the human body that are very similar to those seen during spaceflight, such as bone-mass and muscle-mass loss, cardiovascular and neuro-sensory deconditioning. The controlled bed-rest setting therefore allows meaningful research into the bodily consequences of spaceflight and possible countermeasures. It also gives the scientific community interested in space-related medical research more ready access to a clinical model. The benefits of these studies go far beyond their space application. Patients bed-ridden because of illness or accidents suffer the same symptoms and can thus also profit from the studies. As a clear indication of this link, the clinicians and researchers involved in the bed-rest campaigns typically spend the majority of their time exploring "terrestrial" problems.

Adaptation, Physiological↗

Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations.

In the current report, we provide a quantitative analysis of the convergence of the sampling of conformational space accomplished in molecular dynamics simulations of membrane proteins of duration in the order of 10 nanoseconds. A set of proteins of diverse size and topology is considered, ranging from helical pores such as gramicidin and small beta-barrels such as OmpT, to larger and more complex structures such as rhodopsin and FepA. Principal component analysis of the C(alpha)-atom trajectories was employed to assess the convergence of the conformational sampling in both the transmembrane domains and the whole proteins, while the time-dependence of the average structure was analyzed to obtain single-domain information. The membrane-embedded regions, particularly those of small or structurally simple proteins, were found to achieve reasonable convergence. By contrast, extra-membranous domains lacking secondary structure are often markedly under-sampled, exhibiting a continuous structural drift. This drift results in a significant imprecision in the calculated B-factors, which detracts from any quantitative comparison to experimental data. In view of such limitations, we suggest that similar analyses may be valuable in simulation studies of membrane protein dynamics, in order to attach a level of confidence to any biologically relevant observations.

Computer Simulation↗

Map formation in proprioceptive cortex.

Current understanding of feature maps in proprioceptive cortex is quite limited. To complement experimental studies, we developed a computational model of map formation in proprioceptive cortex. Muscle length and tension from six muscle groups controlling the position of a model arm in three-dimensional space served as input to the simulated cortex. The resultant feature map consisted of regularly spaced clusters of cortical columns representing individual muscle lengths and tensions. Cortical units became tuned to plausible combinations of tension and length, and multiple representations of each muscle group were present. The map was organized such that compact regions within which all muscle group lengths and tensions are represented could be identified. Most striking was the observation that, although not explicitly present in the input, the cortical map developed a representation of the three-dimensional space in which the arm moved. These findings represent testable predictions about proprioceptive cortex, and may also help clarify some organizational issues concerning primary motor cortex.

Arm↗

[Some problems of space medicine].

The paper discusses the problems to be resolved by space medicine and the main stages in the development of this branch of science, beginning with the vertical launches of rockets and ending with the flights of orbital stations. On the basis of ground-based simulation experiments and real space flights it presents a classification of the major symptomocomplexes that may occur inflight. The paper describes the main stages of adaptation to weightlessness and physiological changes in the weightless state. The paper also outlines further pathways in the development of space medicine.

Adaptation, Physiological↗

Phase-space overlap measures. I. Fail-safe bias detection in free energies calculated by molecular simulation.

We consider ways to quantify the overlap of the parts of phase space important to two systems, labeled A and B. Of interest is how much of the A-important phase space lies in that important to B, and how much of B lies in A. Two measures are proposed. The first considers four total-energy distributions, formed from all combinations made by tabulating either the A-system or the B-system energy when sampling either the A or B system. Measures for A in B and B in A are given by two overlap integrals defined on pairs of these distributions. The second measure is based on information theory, and defines two relative entropies which are conveniently expressed in terms of the dissipated work for free-energy perturbation (FEP) calculations in the A-->B and B-->A directions, respectively. Phase-space overlap is an important consideration in the performance of free-energy calculations. To demonstrate this connection, we examine bias in FEP calculations applied to a system of independent particles in a harmonic potential. Systems are selected to represent a range of overlap situations, including extreme subset, subset, partial overlap, and nonoverlap. The magnitude and symmetry of the bias (A-->B vs B-->A) are shown to correlate well with the overlap, and consequently with the overlap measures. The relative entropies are used to scale the amount of sampling to obtain a universal bias curve. This result leads to develop a simple heuristic that can be applied to determine whether a work-based free-energy measurement is free of bias. The heuristic is based in part on the measured free energy, but we argue that it is fail-safe inasmuch as any bias in the measurement will not promote a false indication of accuracy.

Algorithms↗

Structure of Met-enkephalin in explicit aqueous solution using replica exchange molecular dynamics.

Replica exchange molecular dynamics (MD) simulations of Met-enkephalin in explicit solvent reveal helical and nonhelical structures. Four predominant structures of Met-enkephalin are sampled with comparable probabilities (two helical and two nonhelical). The energy barriers between these configurations are low, suggesting that Met-enkephalin switches easily between configurations. This is consistent with the requirement that Met-enkephalin be sufficiently flexible to bind to several different receptors. Replica exchange simulations of 32 ns are shown to sample approximately five times more configurational space than constant temperature MD simulations of the same duration. The energy landscape for the replica exchange simulation is presented. A detailed study of replica trajectories demonstrates that the significant increases in temperature provided by the replica exchange technique enable transitions from nonhelical to helical structures that would otherwise be prevented by kinetic trapping. Met-enkephalin (Type Entrez Proteins; Value A61445; Service Entrez Proteins).

Algorithms↗

Applications of parallel computing to biological problems.

Parallel computers should provide the greatest processing power and memory for scientific simulations in the coming decades. This review discusses general strategies and specific algorithms for the use of various parallel architectures in simulations of biological and artificial polymers. General strategies include space partitioning (domain decomposition cell methods) and distributed independent simulations. Specific algorithms include cellular automata for efficient abstract polymer simulation. One algorithm, the two-space algorithm, is particularly efficient both for parallel and serial computation. Three applications, 2D melts, gel electrophoresis, and polymer collapse, are described. Simulations of high-density melts in 2D show that contrary to expectations, polymers do not completely segregate at the highest densities; instead, polymer interpenetration is significant. Preliminary simulations of gel electrophoresis show its behavior in the diffusive regimen and demonstrate the use of Cellular Automaton Machines (CAMs). Polymer collapse is studied in the regime of large departures from good solvent conditions. In this regime, kinetics plays a significant role. Collapse is dominated (nucleated) by migration of the chain ends.

Algorithms↗

Effects of organelle shape on fluorescence recovery after photobleaching.

The determination of diffusion coefficients from fluorescence recovery data is often complicated by geometric constraints imposed by the complex shapes of intracellular compartments. To address this issue, diffusion of proteins in the lumen of the endoplasmic reticulum (ER) is studied using cell biological and computational methods. Fluorescence recovery after photobleaching (FRAP) experiments are performed in tissue culture cells expressing GFP-KDEL, a soluble, fluorescent protein, in the ER lumen. The three-dimensional (3D) shape of the ER is determined by confocal microscopy and computationally reconstructed. Within these ER geometries diffusion of solutes is simulated using the method of particle strength exchange. The simulations are compared to experimental FRAP curves of GFP-KDEL in the same ER region. Comparisons of simulations in the 3D ER shapes to simulations in open 3D space show that the constraints imposed by the spatial confinement result in two- to fourfold underestimation of the molecular diffusion constant in the ER if the geometry is not taken into account. Using the same molecular diffusion constant in different simulations, the observed speed of fluorescence recovery varies by a factor of 2.5, depending on the particular ER geometry and the location of the bleached area. Organelle shape considerably influences diffusive transport and must be taken into account when relating experimental photobleaching data to molecular diffusion coefficients. This novel methodology combines experimental FRAP curves with high accuracy computer simulations of diffusion in the same ER geometry to determine the molecular diffusion constant of the solute in the particular ER lumen.

Animals↗

Metabolic energy required for flight.

This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in space and their roles in energy metabolism during space flight.

Amino Acids↗

Laboratory simulation of organic grain mantles.

The most relevant conditions in interstellar space for grain mantle evolution are being simulated at Laboratory Astrophysics. In particular we have photoproduced in the laboratory a material resembling the organic refractory mantle on interstellar grains. These organic refractory samples are being analyzed by several methods, and they have been found to consist of a very complex mixture of long chains, cross-linked and probably aromatic carbon molecules.

Ammonia↗

Microvascular exchange and interstitial volume regulation in the rat: model validation.

A dynamic mathematical model is formulated and used to describe the distribution and transport of fluid and plasma proteins between the circulation, interstitial space of skin and muscle, and the lymphatics in the rat. Two descriptions of transcapillary exchange are investigated: a homoporous "Starling model" and a heteroporous "plasma leak model." Parameters used in the two hypothetical transport mechanisms are determined based on statistical fitting procedures between simulation predictions and selected experimental data. These data consist of interstitial fluid volume and colloid osmotic pressure measurements as a function of venous pressure for muscle and interstitial colloid osmotic pressure vs. venous pressure for skin. The values determined for the transport parameters compare well with data in the literature. The fully determined model is used to simulate steady-state conditions of hypoproteinemia, overhydration, and dehydration, as well as the dynamic response to changes in venous pressure and intravascularly administered protein tracers. Comparisons between the simulation predictions and experimental data for these various perturbations are made. The plasma leak model appears to provide a better description of microvascular exchange.

Algorithms↗

Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport.

AIM: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule. METHODS: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species: Na+, K+, Cl- and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace with luminal and peritubular baths of identical composition. RESULTS: The model of the tubular epithelium with physiological water permeability and paracellular electrical resistance generates solute coupled water uptake with an approx. 3% hypertonic absorbate. This function remains unperturbed following 'blocking' of apical water channels and in 'aquaporin-null' simulation. Reduced rate of volume reabsorption in AQP(-/-) mice would also require decreased apical sodium permeability. Paracellular convection accounts for approx. 36% of the net Na+ absorption, and the model epithelium accomplishes uphill water transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane. CONCLUSION: Our model based on solute-solvent coupling in lateral space simulates major physiological features of proximal tubule, including significantly lower water permeability of the AQP1-null preparation, and a ratio of net sodium uptake and oxygen consumption exceeding that predicted from stoichiometry of the Na+/K+-pump. Physical properties of interspace basement membrane are critical for obtaining near-isotonic and truly isotonic transport.

Animals↗

[Fundamental and clinical studies of ceftizoxime in obstetrical and gynecological field].

This paper, is concerned with fundamental and clinical studies of ceftizoxime, a newly developed cephalosporin derivative, in the field of obstetrics and gynecology. 1. Concentrations of ceftizoxime after administration 1 g of ceftizoxime by 1 hour drip infusion were determined in genital organs in 17 patients and the exudate of pelvic dead space in 6 patients. Simulated maximal concentrations with the ratios to the simulated peak serum levels were as follows: 27.9 micrograms/g for fundal myometrium with the ratio of 48%, 36.0 micrograms/g for portio vaginalis with 62%, 17.1 micrograms/g for ovary with 29%, 15.0 micrograms/g for oviduct with 26% and 16.2 micrograms/ml for the exudate of pelvic dead space with 30%. 2. Minimal inhibitory concentrations of ceftizoxime were determined against clinically isolated organisms from female genital infectious diseases. Ceftizoxime was found to have a potent in vitro activity against Gram negative bacilli; for example, 0.1 microgram/mg or low against E. coli and K. pneumoniae. Against P. aeruginosa, P. cepacia and b. fragilis, ceftizoxime had an activity which expected to be effective in the clinical use. 3. We gave ceftizoxime to 6 patients comprising 4 patients with puerperal fever, 1 with septic abortion and 1 with tubo-ovarian abscess in daily doses of 2 to 3 g by b.i.d or t.i.d intravenous drip infusion for 4--12 days. The results of the treatment were 'excellent' in 3 patients, 'good' in 2, and 'unevaluatable' in 1. 4. Adverse reactions occurred in 2 patients who showed eruption during the medication with ceftizoxime. These patients had allergic histories due to penicillin derivatives. From the above results it is concluded that ceftizoxime is a useful drug for infections in obstetrical and gynecological field.

Adult↗

Cellular automaton simulation of pulsed field gel electrophoresis.

We describe simulation techniques well suited to detailed investigation of the microscopic behavior of DNA during electrophoretic separation in the diffusive regime. Long polymers moving diffusively in a medium are simulated using microscopic Monte-Carlo steps. Simulations rely upon a recently introduced two-space abstract polymer that enables fine-grained massively parallel simulation. Tests of the two-space polymer dynamics are reviewed. The scaling with polymer length of the size and relaxation time of isolated polymers are shown to agree with universal scaling relations. The relaxation time is found to be significantly faster than the alternative bond-fluctuation method. Simplicity of implementation enables simulation on cellular automaton machines (CAM) including CAM-6, and a prototype of the new CAM-8, as well as other massively parallel architectures. Preliminary simulations of polymers migrating under an external field through a random medium of obstacles in two dimensions are described. Two sequences of simulations are performed, with different obstacle densities corresponding to pore sizes larger and smaller than the polymer radius of gyration. In the dilute medium polymers are characteristically draped on single obstacles. In the denser medium draping across multiple obstacles results in reduced orientation in the field direction. A demonstration of rapid 90 degrees field direction switching results in polymer motion toward the expected intermediate direction.

Algorithms↗