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Texture of B-mode echograms: 3-D simulations and experiments of the effects of diffraction and scatterer density.

B-mode echograms were simulated by employing the impulse response method in transmission and reception using a discrete scatterer tissue model, with and without attenuation. The analytic signal approach was used for demodulation of the RF A-mode lines. The simulations were performed in 3-D space and compared to B-mode echograms obtained from experiments with scattering tissue phantoms. The average echo amplitude appeared to increase towards the focus and to decrease beyond it. In the focal zone, the average amplitude increased proportionally to the square root of the scatterer density. The signal to noise ratio (SNR) was found to be independent of depth, i.e., 1.91 as predicted for a Rayleigh distribution of gray levels, although a minimum was found in the focal zone at relatively low scatterer densities. The SNR continuously increased with increasing scatterer density and reached the limit of 1.91 at relatively high densities (greater than 10(4) cm-3). The lateral full width at half maximum (FWHM) of the two dimensional autocovariance function of the speckle increased continuously from the transducer face to far beyond the focus and decreased thereafter due to the diffraction effect. The lateral FWHM decreased proportionally to the logarithm of the scatterer density at low densities and reached a limit at high densities. Introduction of attenuation in the simulated tissue resulted in a much more pronounced depth dependence of the texture. The axial FWHM was independent of the distance to the transducer to a first approximation and decreased slightly with increasing scatterer density until a limit was reached at densities larger than 10(3) cm-3. This limit was in agreement with theory. The experiments confirmed the simulations and it can be concluded that the presented results are of great importance to the understanding of B-mode echograms and to the potential use of the analysis of B-mode texture for tissue characterization.

Mathematics↗

Evaluating changes of writhe in computer simulations of supercoiled DNA.

We compute changes in the writhe of a polygonal space curve when one of the vertices is displaced. The resulting expressions can be used in simulations of supercoiled DNA. For Brownian dynamics simulations, the expressions can be used to eliminate the explicit twisting degree of freedom. For Monte Carlo simulations, they can be used in fast local moves. Preliminary Monte Carlo simulations using only such fast local moves show that these can be used to efficiently simulate small DNA supercoils.

Algorithms↗

Engineering and simulation of life sciences Spacelab experiments.

The third in a series of Spacelab Mission Development tests was conducted at the Johnson (correction of Johnston) Space Center as a part of the development of Life Sciences experiments for the Space Shuttle era. The latest test was a joint effort of the Ames Research and Johnson Space Centers and utilized animals and men for study. The basic objective of this test was to evaluate the operational concepts planned for the Space Shuttle life science payloads program. A three-man crew (Mission Specialist and two Payload Specialists) conducted 26 experiments and 12 operational tests, which were selected for this 7-day mission simulation. The crew lived on board a simulated Orbiter/Spacelab mockup 24 hr a day. The Orbiter section contained the mid deck crew quarters area, complete with sleeping, galley and waste management provisions. The Spacelab was identical in geometry to the European Space Agency Spacelab design, complete with removable rack sections and stowage provisions. Communications between the crewmen and support personnel were configured and controlled as currently planned for operational shuttle flights. For this test a Science Operations Remote Center was manned at the Ames Research Center and was managed by simulated Mission Control and Payload Operation Control Centers at the Johnson Space Center. This paper presents the test objectives, description of the facilities and test program, and the results of this test.

Animals↗

Physiologically based modeling of the accumulation in plasma and tissue lipids of a mixture of PCB congeners in female Sprague-Dawley rats.

This study aimed to develop a physiologically based model for simulating the concentrations of polychlorinated biphenyls (PCBs) in tissue and plasma lipids of rats exposed to PCB mixtures. The model was based on the assumption that the neutral lipid fraction is the only critical determinant of the tissue distribution of PCBs, and that the solubility/retention in other tissue components is negligible. The volumes of the model compartments reflected the volumes of neutral lipids, whereas the flow rates corresponded to those of the neutral lipids in blood. Since the equilibrium ratio of PCB concentrations in neutral lipids of tissues and plasma equals 1, the present modeling approach does not require the use of tissue:blood partition coefficients. Metabolism rates were derived from the best visual fit of the model to the PCB concentrations in hepatic lipids determined on d 41 and 90 in rats exposed to a mixture containing 5, 50, or 500 microg PCBs (118, 138, 153, 170, 180 and 187) per kilogram body weight according to various protocols: (a) every-day dosing, (b) once-a-week dosing, (c) consecutive dosing for 13 d with no further treatment, and (d) 13 irregularly spaced doses. The resulting model consistently simulated the concentrations of PCBs in adipose tissue and plasma lipids of rats exposed according to the four described protocols. The physiologically based pharmacokinetic (PBPK) model developed in this study should be useful as a basis for interpretating blood or plasma lipid concentration data on PCBs collected during biomonitoring studies.

Adipose Tissue↗

[Individual style of communication with the outer world during long-term isolation].

Crew communication with ground controllers is a source of information for diagnostics of mood, mental performance and mutual understanding within space crew. The article analyzes results of dynamic observation of communication of small groups isolated from the outer world during project SFINCSS-99 performed at RF SSC-IBMP in 1999-2000 with the purpose to simulate life and interrelations within ISS crews. The project evidenced that some communication manners featured personal strategies of adaptation to the extreme conditions. A modified procedure of communication content-analysis proved to be a success in remote psychodiagnostics and to bear promise for analysis of crew personality and inter-relationship during space flight.

Adaptation, Physiological↗

Human sensorimotor coordination following space flights.

Studies have been carried out 18-30 days before the flight and on the second day after landing. The recovery kinetics of cosmonauts who completed the 18-day space flight was followed for 30 days after their return. Muscle tone, indices of muscle strength and parameters of the functions of the extremities were examined, and the ability to maintain vertical posture was studied (stabilography). Flights of short duration did not cause any serious disturbances in the neuromuscular system. Together with this fact, the analysis of the results revealed a certain regularity in the physiological effects as reflected by a decrease in the strength of the torso extensors and the muscle tone of the lower extremities, The tone and strength of the arms altered insignificantly, and the alterations were not an indication of muscular atrophy. Stabilographic studies showed a decrement in the stability of the vertical posture of the cosmonauts. The above alterations were particularly pronounced in the crew members of Soyuz 9. As distinct from the previous flights of the Soyuz spaceships the crew members of Soyuz 9 showed normality in the regulation of vertical posture only on the tenth day after the flight. One of the reasons for the above alterations in postural regulation may be the decrease in muscle tone noted repeatedly after both of the previous space flights and in experiments with simulation of separate effects of weightlessness. Another reason for the deterioration in postural regulation is probably the changes in interaction between the neutral analysers. A possible reason for the apparent defects in stability may be the disturbance of the interaction between various muscle groups, i.e. the disturbance in synergism which is required for the maintenance of vertical posture. Similar alterations were observed in people who had been subjected to bed rest for a long time. Readaptation to the ground environment appeared to proceed in stages. The comparative evaluation of post-flight findings showed that prolonged periods of flights up to 18 days resulted in more pronounced alterations in human sensomotor coordination.

Adaptation, Physiological↗

Centrifugation as a countermeasure during actual and simulated microgravity: a review.

This paper summarizes what has been learned from studies of the effects of artificial gravity generated by centrifugation in actual and simulated weightless conditions. The experience of artificial gravity during actual space flight in animals and humans are discussed. Studies using intermittent centrifugation during bed rest and water immersion, as a way to maintain orthostatic tolerance and exercise capacity, are reviewed; their results indicate that intermittent centrifugation is a potential countermeasure for maintaining the integrity of these physiological functions in extended space missions. These results can help set guidelines for future experiments aimed at validating the regimes of centrifugation as a countermeasure for space missions. Current and future research projects using artificial gravity conditions in humans are discussed.

Animals↗

Ephaptic interactions in the mammalian olfactory system.

Ephaptic coupling refers to interactions between neurons mediated by current flow through the extracellular space. Ephaptic interactions between axons are considered negligible, because of the relatively large extracellular space and the layers of myelin that separate most axons. By contrast, olfactory nerve axons are unmyelinated and arranged in tightly packed bundles, features that may enhance ephaptic coupling. We tested the hypothesis that ephaptic interactions occur in the mammalian olfactory nerve with the use of a computational approach. Numerical solutions of models of axon fascicles show that significant ephaptic interactions occur for a range of physiologically relevant parameters. An action potential in a single axon can evoke action potentials in all other axons in the fascicle. Ephaptic interactions can also lead to synchronized firing of independently stimulated axons. Our findings suggest that ephaptic interactions may be significant determinants of the olfactory code and that such interactions may occur in other, similarly organized axonal or dendritic bundles.

Action Potentials↗

Spin-labeled nucleotide mobility in the boundary of the EcoRI endonuclease binding site.

A complex consisting of the EcoRI endonuclease site-specifically bound to spin-labeled DNA 26mers was prepared to provide a model system for studying possible conformational changes resulting from protein binding. EPR was used to monitor the mobility of the spin labels that were strategically placed in position 6, 9, or 11 with respect to the dyad axis of the 26mer. These positions are located within the flanking region on either side of the EcoRI hexamer binding site. This allows the monitoring of potential distal structural changes in the DNA helix caused by protein binding. The spectral line shapes indicate that the spin label closest to the EcoRI endonuclease binding site, i.e., in position 6, is most influenced by the binding event. The EPR data are analyzed according to a model that distinguishes between spectral effects due to a change in the hydrodynamic shape of the complex and those resulting from local variations in the spin-label mobility as characterized by a local order parameter S. S reflecting the motional restriction of the spin-labeled base is 0.20 +/- 0.01 for all three oligomers as well as for the two complexes with the label in position 9 or 11, while the position 6 labeled complex yields S = 0.25. To further evaluate the origin of the slightly larger EPR effect observed with position 6 labeled material, molecular dynamics (MD) simulations were used to explore the space accessible to the probes in positions 6, 9, and 11. MD results gave similar nitroxide trajectories for all three labeled 26mers in the absence or presence of EcoRI. Thus, the small position 6 effect is attributed to a structural distortion in the major groove of the DNA at this location possibly corresponding to a bend induced by protein binding. The observation that the spectral changes are small indicates the absence of any significant structural disruption being propagated along the helix as a result of protein binding. Also, the fact that the line shape of the 26mers did not change as expected from hydrodynamic theory in view of the significant increase in molecular volume upon protein binding suggests that there are additional relaxation processes involving the protein and nucleic acid.

Binding Sites↗

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats.

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Adaptation, Physiological↗

Simulating colonial growth of fungi with the Neighbour-Sensing model of hyphal growth.

The Neighbour-Sensing model brings together the basic essentials of hyphal growth kinetics into a vector-based mathematical model in which the growth vector of each virtual hyphal tip is calculated by reference to the surrounding virtual mycelium. The model predicts the growth pattern of many hyphae into three spatial dimensions and has been used to simulate complex fungal fruit body shapes. In this paper we show how the Neighbour-Sensing model can simulate growth in semi-solid substrata like agar or soil, enabling realistic simulation of mycelial colonies of filamentous fungi grown in 'Petri-dish style' experimental conditions. Newly implemented capabilities in the model include: a measurement and logging system within the program that maintains basic statistics about the mycelium it is simulating, this facilitates kinetic experimentation; inclusion of 'substrates' in the data space causing positive or negative tropisms for the growing mycelium; a horizontal plane tropism that provides a way of simulating colonies growing in or on a substratum like agar or soil by imposing a horizontal constraint on the data space the cyberhyphal tips can explore; three categories of hypha--standard hyphae are those that start the simulation, leading hyphae can emerge from the colony peripheral growth zone to take on a leading role, and secondary hyphae are branches that can arise late, far behind the peripheral growth zone, when mature hyphal segments resume branching to in-fill the older parts of the colony. We show how the model can be used to investigate hyphal growth kinetics in silico in experimental scenarios that would be difficult or impracticable in vivo. We also show that the Neighbour-Sensing model can generate sufficiently realistic cord-like structures to encourage the belief that this model is now sufficiently advanced for parameters to be defined that simulate specific in silico cyberfungi. The potential utility of these cyberspecies is that they provide a means to model the morphogenetic effects of a variety of factors, from environmental and nutritional features to mutations, in experimentally realistic situations, offering a valuable addition to the experimental toolkit of all those interested in fungal growth and morphology.

Computer Graphics↗

Monte Carlo simulation of a clinical linear accelerator.

The effects of the physical parameters of an electron beam from a Siemens PRIMUS clinical linear accelerator (linac) on the dose distribution in water were investigated by Monte Carlo simulation. The EGS4 user code, OMEGA/BEAM, was used in this study. Various incident electron beams, for example, with different energies, spot sizes and distances from the point source, were simulated using the detailed linac head structure in the 6 MV photon mode. Approximately 10 million particles were collected in the scored plane, which was set under the reticle to form the so-called phase space file. The phase space file served as a source for simulating the dose distribution in water using DOSXYZ. Dose profiles at Dmax (1.5 cm) and PDD curves were calculated following simulating about 1 billion histories for dose profiles and 500 million histories for percent depth dose (PDD) curves in a 30 x 30 x 30 cm3 water phantom. The simulation results were compared with the data measured by a CEA film and an ion chamber. The results show that the dose profiles are influenced by the energy and the spot size, while PDD curves are primarily influenced by the energy of the incident beam. The effect of the distance from the point source on the dose profile is not significant and is recommended to be set at infinity. We also recommend adjusting the beam energy by using PDD curves and, then, adjusting the spot size by using the dose profile to maintain the consistency of the Monte Carlo results and measured data.

Computer Simulation↗

Changes in diffusion through the brain extracellular space.

ECS (extracellular space) works as the microenvironment of brain cells. Diffusion through ECS may be described through an effective diffusion coefficient, D (e), which in turn depends on ECS porosity, epsilon, and tortuosity, T. In the present research, diffusion data together with epsilon and T were collected from the specialized literature and analysed to seek a correlation of T versus epsilon. On the basis of D (e) data, upper and lower T boundaries were defined and related to topologically 'dense' and 'loose' cell arrangement. A possible range for T variation was obtained for ECS, with epsilon ranging from 0.05 to 0.6. A tortuosity index ( n ) in the form of T and epsilon logarithmic ratio was introduced. This index may be adopted for recalculation of T or epsilon if only one of these parameters is known. As a result of data analysis and modelling, it was concluded that, upon different external conditions, for instance oxygen depletion, the ECS porosity decreases and cells (presumably through membrane rearrangements) adjust the void space to keep the diffusion within a defined range, which gives the living tissue the ability to maintain the diffusion level up to two or more times higher than in conventional granular bed packing. Thus, even with a dramatic ECS decrease, the cellular system is still able to support a given diffusion by decreasing the value of T. The obtained results clearly show the existence of three data clusters: a region of normal brain functioning, both for young and adult brains, for values of epsilon comprised between 0.15 and 0.30, and two regions of abnormal brain behaviour to the left and to the right of the normal region, corresponding to different states (aging, tumours, anoxia, brain death, etc.). The present approach allows defining the optimal range of epsilon and T to assure the best ECS diffusion efficiency for a specified macromolecule. This might be important in brain clinical treatment.

Animals↗

Structural basis of hierarchical multiple substates of a protein. II: Monte Carlo simulation of native thermal fluctuations and energy minimization.

Conformational fluctuations in a globular protein, bovine pancreatic trypsin inhibitor, in the time range between picoseconds and nanoseconds are studied by a Monte Carlo simulation method. Multiple energy minima are derived from sampled conformations by minimizing their energy. They are distributed in clusters in the conformational space. A hierarchical structure is observed in the simulated dynamics. In the time range between 10(-14) and 10(-10) seconds dynamics is well represented by a superposition of vibrational motions within an energy well with transitions among minima within each cluster. Transitions among clusters take place in the time range of nanoseconds or longer.

Animals↗

Terrestrial applications of bone and muscle research in microgravity.

Major applications to people on Earth are possible from NASA-sponsored research on bone and muscle which is conducted either in microgravity or on Earth using models mimicking microgravity. In microgravity bone and muscle mass are lost. Humans experience a similar loss under certain conditions on Earth. Bone and muscle loss exist on Earth as humans age from adulthood to senescence, during limb immobilization for healing of orthopedic injuries, during wheelchair confinement because of certain diseases, and during chronic bed rest prescribed for curing of diseases. NASA-sponsored research is dedicated to learning both what cause bone and muscle loss as well as finding out how to prevent this loss. The health ramifications of these discoveries will have major impact. Objective 1.6 of Healthy People 2000, a report from the U.S. Department of Health and Human Services, states that the performance of physical activities that improve muscular strength, muscular endurance, and flexibility is particularly important to maintaining functional independence and social integration in older adults. This objective further states that these types of physical activities are important because they may protect against disability, an event which costs the U.S. economy huge sums of money. Thus NASA research related to bone and muscle loss has potential major impact on the quality of life in the U.S. Relative to its potential health benefits, NASA and Congressional support of bone and muscle research is funded at a very low level.

Adult↗

Protein dynamics simulations from nanoseconds to microseconds.

There have been a number of advances in atomic resolution simulations of biomolecules during the past few years. These have arisen partly from improvements to computer power and partly from algorithmic improvements. There have also been advances in measuring time-dependent fluctuations in proteins using NMR spectroscopy, revealing the importance of fluctuations in the microsecond to millisecond time range. Progress has also been made in measuring how far the simulations are able to represent the accessible phase space that is available to the protein in its native state, in solution, at room temperature. Another area of development is the simulation of protein unfolding at atomic resolution.

Algorithms↗

Effects of low-shear modeled microgravity on cell function, gene expression, and phenotype in Saccharomyces cerevisiae.

Only limited information is available concerning the effects of low-shear modeled microgravity (LSMMG) on cell function and morphology. We examined the behavior of Saccharomyces cerevisiae grown in a high-aspect-ratio vessel, which simulates the low-shear and microgravity conditions encountered in spaceflight. With the exception of a shortened lag phase (90 min less than controls; P < 0.05), yeast cells grown under LSMMG conditions did not differ in growth rate, size, shape, or viability from the controls but did differ in the establishment of polarity as exhibited by aberrant (random) budding compared to the usual bipolar pattern of controls. The aberrant budding was accompanied by an increased tendency of cells to clump, as indicated by aggregates containing five or more cells. We also found significant changes (greater than or equal to twofold) in the expression of genes associated with the establishment of polarity (BUD5), bipolar budding (RAX1, RAX2, and BUD25), and cell separation (DSE1, DSE2, and EGT2). Thus, low-shear environments may significantly alter yeast gene expression and phenotype as well as evolutionary conserved cellular functions such as polarization. The results provide a paradigm for understanding polarity-dependent cell responses to microgravity ranging from pathogenesis in fungi to the immune response in mammals.

Biomechanical Phenomena↗

A restraint molecular dynamics and simulated annealing approach for protein homology modeling utilizing mean angles.

BACKGROUND: We have developed the program PERMOL for semi-automated homology modeling of proteins. It is based on restrained molecular dynamics using a simulated annealing protocol in torsion angle space. As main restraints defining the optimal local geometry of the structure weighted mean dihedral angles and their standard deviations are used which are calculated with an algorithm described earlier by Doker et al. (1999, BBRC, 257, 348-350). The overall long-range contacts are established via a small number of distance restraints between atoms involved in hydrogen bonds and backbone atoms of conserved residues. Employing the restraints generated by PERMOL three-dimensional structures are obtained using standard molecular dynamics programs such as DYANA or CNS. RESULTS: To test this modeling approach it has been used for predicting the structure of the histidine-containing phosphocarrier protein HPr from E. coli and the structure of the human peroxisome proliferator activated receptor gamma (Ppar gamma). The divergence between the modeled HPr and the previously determined X-ray structure was comparable to the divergence between the X-ray structure and the published NMR structure. The modeled structure of Ppar gamma was also very close to the previously solved X-ray structure with an RMSD of 0.262 nm for the backbone atoms. CONCLUSION: In summary, we present a new method for homology modeling capable of producing high-quality structure models. An advantage of the method is that it can be used in combination with incomplete NMR data to obtain reasonable structure models in accordance with the experimental data.

Algorithms↗