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PubMed2004

The autonomous regulation system functional reserves evaluation in 7-day head down bedrest.

The heart rate variability estimation was used for autonomous regulation diagnostic in the 7-day head down bedrest experiment (HDBR). The new device "Pneumocard" and the fix respirations test were applied. The growth of sympathetic activity of autonomous nervous system and reduction of functional reserves of regulation mechanisms were observed in the microgravity modeling by HDBR. The analysis of the individual data had shown, that at two volunteers with most significant growth of SI after the experiment the orthostatic intolerance was observed. The data received in experiment confirm a hypothesis that growth of sympathetic activity in microgravity is accompanied by reduction of regulation mechanisms functional reserves is prognostic unfavorable.

Aerospace Medicine↗

PubMed1992

Enhanced induction of a 72 kDa heat shock protein in cultured retroocular fibroblasts.

Fibroblasts in the retroocular connective tissue appear to play a central role in the pathogenesis of Graves' ophthalmopathy (GO). We hypothesize that specific attributes, differentiating normal from GO retroocular fibroblasts, may render the latter more vulnerable to the ongoing immunopathological process in GO. We investigated whether GO fibroblasts differ from normal fibroblasts with respect to their sensitivity and capacity to express the inducible 72 kDa heat shock protein (HSP) in response to stressful environmental stimuli. Cultured retroocular fibroblasts derived from patients with GO and normal individuals were exposed to various changes in the culture medium that may simulate conditions in the affected retroocular space in vivo. HSP 72 reactivity was determined using sodium dodecyl sulfate polyacrylamide-gel electrophoresis of cellular extracts, followed by immunoblotting with a mouse monoclonal anti-HSP 72 antibody and quantitative scanning densitometry. In addition, indirect immunofluorescence was performed on parallel fibroblast monolayers. Following exposure to heat and acidic pH, deprivation from nutrients, and high monolayer density, GO fibroblasts expressed HSP 72 with significantly greater sensitivity and in significantly higher abundance than did normal fibroblasts. These results demonstrate that changes in the physiological environment induce HSP 72 expression in cultured fibroblasts. The enhanced sensitivity and capacity of GO retroocular fibroblasts to express the inducible HSP 72 in response to stressful stimuli may play a role in the autoimmune process affecting the retroocular space in GO.

Autoimmune Diseases↗

PubMed1991

[Organized follicular cyst simulating a sinus lesion].

Follicular cyst is a frequent lesion rich in cholesterine and methemoglobin. These cysts produce T1 shortening and a high intensity signal on T1-weighted imaging. The most frequent location is the lower mandibular ramus. Sometimes, it occurs in the maxillar with possible involvement of the paranasal sinuses simulating a mucocele or a space-occupying lesion of the sinus.

Diagnosis, Differential↗

PubMed1986

Biological and technological variability of residual lung volume and the effect on body fat calculations.

Ten subjects were studied to determine within-subject variance (Swi2), and its components, biovariability (Si2) and technological error (Se2) of residual lung volume (RLV). Each subject's RLV was determined 18 times using the oxygen dilution method (O2D) over a 5-day period. Se2 was measured using a 9.0 l spirometer as a simulated subject and estimating its added space by the O2D method for 20 repeat trials. The mean +/- SD of RLV across subjects was 1.408 +/- 0.3143 l. The average Swi2 for the 18 trials was 0.0054 (Swi = +/- 0.0735 l). The variance associated with a trend effect (variance of mean trial scores, Sc2) was 0.00050 (Sc = +/- 0.0224 l). Se2 was found to be 0.00104 (Se = +/- 0.0323 l). Si2 calculated by subtracting Se2 and Sc2 from Swi2, was 0.0039 (Si = +/- 0.0621 l). It was demonstrated that body fat weight calculations can vary because of the within-subject variability in RLV. The calculated reliability of RLV across subjects was r = 0.95. It is concluded that RLV determined by the O2D method is very reliable. Moreover, biological variance accounts for 72% of Swi2 while technological variance and trend effect variance account for 19 and 9% of Swi2 respectively.

Adult↗

PubMedDate not supplied

Compact compliance chamber design for the study of cardiac performance in microgravity.

A need was identified for a Mock Circulation System (MCS) of small size and weight that could function in a microgravity environment for the investigation of cardiovascular response to the weightlessness of space flight. Part of the MCS development involved the redesign of the compliance chamber from a Penn State MCS using a coil spring instead of the leaf spring system employed in the Penn State system. The new compliance chambers achieve a weight reduction of 47% and a volume reduction of 64% over the original Penn State design. Testing showed the coil spring compliance chambers retained physiologic characteristics and adjustability by using coil springs of various stiffness, and functioned equivalently to the original Penn State design.

Biomechanical Phenomena↗

PubMed1988

Biomedical support of man in space.

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.

Adaptation, Physiological↗

PubMedDate not supplied

Effect of simulated and real weightlessness on early regeneration stages of Brassica napus protoplasts.

Results from experiments using protoplasts in space, performed on the Biokosmos 9 satellite in 1989 and on the Space Shuttle on the IML-1-mission in 1992 and S/MM-03 in 1996, are presented. This paper focuses on the observation that the regeneration capacity of protoplasts is lower under micro-g conditions than under 1 g conditions. These aspects have been difficult to interpret and raise new questions about the mechanisms behind the observed effects. In an effort to try to find a key element to the poor regeneration capacity, ground-based studies were initiated focusing on the effect of the variable organization and quantity of corticular microtubules (CMTs) as a consequence of short periods of real and simulated weightlessness. The new results demonstrated the capacity of protoplasts to enter division, confirming the findings in space that this was affected by gravity. The percentage of dividing cells significantly decreased as a result of exposure to simulated weightlessness on a 2-D clinostat. Similar observations were made when comparing the wall components, which confirmed that the reconstitution of the cell wall was retarded under both space conditions and simulated weightlessness. The peroxidase activity in protoplasts exposed to microgravity was slightly decreased in both 0 g and 1 g flight samples compared with the ground controls, whereas activity in the protoplasts exposed to simulated weightlessness was similar to activity in the 1 g control. The observation that protoplasts had randomized and more sparse corticular microtubules when exposed to various forms of simulated and real weightlessness on a free-fall machine on the ground could indicate that the low division capacity in 0 g protoplasts was correlated with an abnormal CMT array in these protoplasts. This study has increased our knowledge of the more basic biochemical and cell biological aspects of g effects. This is an important link in preparation for the new space era, when it will be possible to follow the growth of single cells and tissue cultures for generations under microgravity conditions on the new International Space Station, which will be functional on a permanent basis from the year 2003.

Brassica napus↗

PubMed1995

Glutathione depletion kinetics with acetaminophen. A simulation study.

A tubular-flow model with known published parameters on glutathione (GSH) synthesis, degradation, and transport was developed to examine the distributed-in-space bimolecular reaction of GSH conjugation with acceptor substrates. Simulations were performed to obtain the vascular and intracellular GSH concentrations in the absence and presence of acetaminophen. Zonal localization of GSH was found to be effectively modified upon varying the activities for GSH synthesis and degradation along the sinusoidal flow path. A periportal (zone 1) GSH distribution resulted when GSH synthetic activity was distributed anterior to the degradation activity (models A and D); a perivenous (zone 3) GSH enrichment existed when these activities were reversed (model B), whereas when the synthetic and degradation activities for GSH were homogeneously distributed (model C), GSH concentration was unchanged in all zones. Although the zonation of GSH was model-dependent (models A-D ), only minor differences were found to exist for the length-averaged tissue GSH concentration (5.8-6 mumol/g liver) and the outflow of the liver (approximately 15 microM). With acetaminophen, a substrate known to deplete GSH via its reactive intermediate, N-acetyl-p-quinoneimine (NAPQI), acinar GSH patterns were not greatly perturbed at concentrations < 1 mM. At 10 mM acetaminophen, however, differential patterns of GSH zonal depletion were observed among models, although there was virtually no difference in the length-averaged intracellular GSH concentration (3 mumol/g liver) nor in the formation of the acetaminophen GSH adduct, with the latter being rate-limited by the bioactivation of acetaminophen to NAPQI.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed2004

Finite-element modeling of the hemodynamics of stented aneurysms.

BACKGROUND: Computational fluid dynamics (CFD) simulations are used to analyze the wall shear stress distribution and flow streamlines near the throat of a stented basilar side-wall aneurysm. Previous studies of stented aneurysm flows used low mesh resolution, did not include mesh convergence analyses, and depended upon conformal meshing techniques that apply only to very artificial stent geometries. METHOD OF APPROACH: We utilize general-purpose computer assisted design and unstructured mesh generation tools that apply in principle to stents and vasculature of arbitrary complexity. A mesh convergence analysis for stented steady flow is performed, varying node spacing near the stent. Physiologically realistic pulsatile simulations are then performed using the converged mesh. RESULTS: Artifact-free resolution of the wall shear stress field on stent wires requires a node spacing of approximately 1/3 wire radius. Large-scale flow features tied to the velocity field are, however, captured at coarser resolution (nodes spaced by about one wire radius or more). CONCLUSIONS: Results are consistent with previous work, but our methods yield more detailed insights into the complex flow dynamics. However, routine applications of CFD to anatomically realistic cases still depend upon further development of dedicated algorithms, most crucially to handle geometry definition and mesh generation for complicated stent deployments.

Blood Flow Velocity↗

PubMed2002

Contrasting patterns of receptive field plasticity in the hippocampus and the entorhinal cortex: an adaptive filtering approach.

Neural receptive fields are frequently plastic: a neural response to a stimulus can change over time as a result of experience. We developed an adaptive point process filtering algorithm that allowed us to estimate the dynamics of both the spatial receptive field (spatial intensity function) and the interspike interval structure (temporal intensity function) of neural spike trains on a millisecond time scale without binning over time or space. We applied this algorithm to both simulated data and recordings of putative excitatory neurons from the CA1 region of the hippocampus and the deep layers of the entorhinal cortex (EC) of awake, behaving rats. Our simulation results demonstrate that the algorithm accurately tracks simultaneous changes in the spatial and temporal structure of the spike train. When we applied the algorithm to experimental data, we found consistent patterns of plasticity in the spatial and temporal intensity functions of both CA1 and deep EC neurons. These patterns tended to be opposite in sign, in that the spatial intensity functions of CA1 neurons showed a consistent increase over time, whereas those of deep EC neurons tended to decrease, and the temporal intensity functions of CA1 neurons showed a consistent increase only in the "theta" (75-150 msec) region, whereas those of deep EC neurons decreased in the region between 20 and 75 msec. In addition, the minority of deep EC neurons whose spatial intensity functions increased in area over time fired in a significantly more spatially specific manner than non-increasing deep EC neurons. We hypothesize that this subset of deep EC neurons may receive more direct input from CA1 and may be part of a neural circuit that transmits information about the animal's location to the neocortex.

Action Potentials↗

PubMed1995

Use of the Remote Access Virtual Environment Network (RAVEN) for coordinated IVA-EVA astronaut training and evaluation.

This paper presents a unique virtual reality training and assessment tool developed under a NASA grant, "Research in Human Factors Aspects of Enhanced Virtual Environments for Extravehicular Activity (EVA) Training and Simulation." The Remote Access Virtual Environment Network (RAVEN) was created to train and evaluate the verbal, mental and physical coordination required between the intravehicular (IVA) astronaut operating the Remote Manipulator System (RMS) arm and the EVA astronaut standing in foot restraints on the end of the RMS. The RAVEN system currently allows the EVA astronaut to approach the Hubble Space Telescope (HST) under control of the IVA astronaut and grasp, remove, and replace the Wide Field Planetary Camera drawer from its location in the HST. Two viewpoints, one stereoscopic and one monoscopic, were created all linked by Ethernet, that provided the two trainees with the appropriate training environments.

Astronauts↗

PubMed2003

An in silico exploration of the neutral network in protein sequence space.

Designating amino-acid sequences that fold into a common main-chain structure as "neutral sequences" for the structure, regardless of their function or stability, we investigated the distribution of neutral sequences in protein sequence space. For four distinct target structures (alpha, beta,alpha/beta and alpha+beta types) with the same chain length of 108, we generated the respective neutral sequences by using the inverse folding technique with a knowledge-based potential function. We assumed that neutral sequences for a protein structure have Z scores higher than or equal to fixed thresholds, where thresholds are defined as the Z score for the corresponding native sequence (case 1) or much greater Z score (case 2). An exploring walk simulation suggested that the neutral sequences mapped into the sequence space were connected with each other through straight neutral paths and formed an inherent neutral network over the sequence space. Through another exploring walk simulation, we investigated contiguous regions between or among the neutral networks for the distinct protein structures and obtained the following results. The closest approach distance between the two neutral networks ranged from 5 to 29 on the Hamming distance scale, showing a linear increase against the threshold values. The sequences located at the "interchange" regions between the two neutral networks have intermediate sequence-profile-scores for both corresponding structures. Introducing a "ball" in the sequence space that contains at least one neutral sequence for each of the four structures, we found that the minimal radius of the ball that is centered at an arbitrary position ranged from 35 to 50, while the minimal radius of the ball that is centered at a certain special position ranged from 20 to 30, in the Hamming distance scale. The relatively small Hamming distances (5-30) may support an evolution mechanism by transferring from a network for a structure to another network for a more beneficial structure via the interchange regions.

Amino Acid Sequence↗

PubMed1998

Computer simulation as a tool in evaluating intracellular spatial arrangement of an organelle using random section data.

A random profile of a cell gives a highly biased presentation of the location of various organelles within an intracellular space. The technique combining mathematical modeling and computer simulation presented here is aimed to overcome this bias and interpret intracellular spatial arrangement of an organelle using two-dimensional (2-D) observations from random sections. It allows to simulate random sectioning of a cell whose shape approximates to an ellipsoid of rotation, and to obtain the coordinates for the center of an organelle profile located within a cell profile. The pilot study was performed to investigate the influence of different three-dimensional (3-D) scattering patterns of an organelle on the coordinates of an organelle profile's center. Computer tests were carried out on a personal computer using the original software written in Pascal. It was ascertained that statistical properties of a sample of organelle profile's center coordinates allow for a quantitative estimation of some 3-D features, including the position of an organelle with respect to a cell center and specific characteristics of an organelle position (e.g., its fixity or randomness).

Cells↗

PubMed2005

Use of animal models for space flight physiology studies, with special focus on the immune system.

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Animals↗

PubMed2007

Modelling and advanced understanding of unsteady-state gas transfer in shaking bioreactors.

In shaken bioreactors equipped with a sterile closure (e.g. a cotton plug), a realistic understanding and estimation of gas transfer is advantageous to avoid oxygen limitation or carbon dioxide inhibition of a microbial culture. Therefore, in the present study, an unsteady-state gas-transfer model for shake flasks was developed and experimentally investigated for a wide range of gas-transfer resistances (k(plug)). The introduced approach is based on the model of Henzler and co-workers [Henzler and Schedel (1991) Bioprocess Eng. 7, 123-131; Mrotzek, Anderlei, Henzler and Büchs (2001) Biochem. Eng. J. 7, 107-112], which describe the spatially resolved gas partial pressures inside the sterile closure, affecting the local gas diffusion coefficients and convective Stefan flow. For further easy processing the resulting total mass-transfer resistance (k(plug)) is described as a function of the mass flow through the sterile plug (OTR(plug)) by an empirical equation. This equation is introduced into a simulation model which calculates the gas partial pressures in the head space of the flask. Additionally, the gas-transfer rates through the sterile closure and gas/liquid interface inside the flask is provided. Simulations indicate that neglecting the oxygen in the head space volume of the flask under initial conditions (simple steady-state assumption) may lead to an underestimation of the oxygen transfer into the liquid phase. The extension of error depends on the conditions. A good agreement between the introduced unsteady-state model and experimental results for the sulfite oxidation as a chemical model system confirmed the validity and usefulness of the proposed unsteady-state approach.

Bioreactors↗

PubMed2006

Structural transitions of confined model proteins: molecular dynamics simulation and experimental validation.

Proteins fold in a confined space not only in vivo, i.e., folding assisted by molecular chaperons and chaperonins in a crowded cellular medium, but also in vitro as in production of recombinant proteins. Despite extensive work on protein folding in bulk, little is known about how and to what extent the thermodynamics and kinetics of protein folding are altered by confinement. In this work, we use a Gō-like off-lattice model to investigate the folding and stability of an all beta-sheet protein in spherical cages of different sizes and surface hydrophobicity. We find whereas extreme confinement inhibits correct folding, a hydrophilic cage stabilizes the protein due to restriction of the unfolded configurations. In a hydrophobic cage, however, strong attraction from the cage surface destabilizes the confined protein because of competition between self-aggregation and adsorption of hydrophobic residues. We show that the kinetics of protein collapse and folding is strongly correlated with both the cage size and the surface hydrophobicity. It is demonstrated that a cage of moderate size and hydrophobicity optimizes both the folding yield and kinetics of structural transitions. To support the simulation results, we have also investigated the refolding of hen-egg lysozyme in the presence of cetyltrimethylammoniumbromide (CTAB) surfactants that provide an effective confinement of the proteins by micellization. The influence of the surfactant hydrophobicity on the structural and biological activity of the protein is determined with circular dichroism spectrum, fluorescence emission spectrum, and biological activity assay. It is shown that, as predicted by coarse-grained simulations, CTAB micelles facilitate the collapse of denatured lysozyme, whereas the addition of beta-cyclodextrin-grafted-PNIPAAm, a weakly hydrophobic stripper, dissociates CTAB micelles and promotes the conformational rearrangement and thereby gives an improved recovery of lysozyme activity.

Acrylic Resins↗

PubMed2000

[Seasonal evolution of the biogeochemical cycle in the southwest lagoon of New Caledonia. Application of a compartmental model].

A biogeochemical box model describing the south-west lagoon of New-Caledonia was developed in order to simulate the seasonal cycle of carbon and nitrogen. We used fluxes generated by a 3D hydrodynamic model to simulate horizontal exchanges between boxes and added freshwater influxes as nitrogen sources from the land. Average residence time proved to be less than 11 days for the lagoon as a whole. Standard simulations showed baseline values of chlorophyll a between 0.2 and 0.4 microgram.L-1. Influences of freshwater influxes proved to be significant (increases up to 1 microgram.L-1) only in shallow areas protected from wind exposure and during short periods of heavy rainfall (tropical depressions). Tropical climatic events have reduced impact in space and time and long-term simulations over decades with increased nutrient inputs did not show any significant process of eutrophication. Hydrodynamics seemed to be one of the major control factors with respect to organic matter cycling in the lagoon.

Chlorophyll↗

PubMed2003

Space-time relationship in continuously moving table method for large FOV peripheral contrast-enhanced magnetic resonance angiography.

Data acquisition using a continuously moving table approach is a method capable of generating large field-of-view (FOV) 3D MR angiograms. However, in order to obtain venous contamination-free contrast-enhanced (CE) MR angiograms in the lower limbs, one of the major challenges is to acquire all necessary k-space data during the restricted arterial phase of the contrast agent. Preliminary investigation on the space-time relationship of continuously acquired peripheral angiography is performed in this work. Deterministic and stochastic undersampled hybrid-space (x, k(y), k(z)) acquisitions are simulated for large FOV peripheral runoff studies. Initial results show the possibility of acquiring isotropic large FOV images of the entire peripheral vascular system. An optimal trade-off between the spatial and temporal sampling properties was found that produced a high-spatial resolution peripheral CE-MR angiogram. The deterministic sampling pattern was capable of reconstructing the global structure of the peripheral arterial tree and showed slightly better global quantitative results than stochastic patterns. Optimal stochastic sampling patterns, on the other hand, enhanced small vessels and had more favourable local quantitative results. These simulations demonstrate the complex spatial-temporal relationship when sampling large FOV peripheral runoff studies. They also suggest that more investigation is required to maximize image quality as a function of hybrid-space coverage, acquisition repetition time and sampling pattern parameters.

Algorithms↗