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At least 793 records · Page 44Linked to original sources
PubMed2002

Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia.

Glutamate release in ischaemia triggers neuronal death. The major glial glutamate transporter, GLT-1, might protect against glutamate-evoked death by removing extracellular glutamate, or contribute to death by reversing and releasing glutamate. Previous studies of the role of GLT-1 in ischaemia have often used the GLT-1 blocker dihydrokainate at concentrations that affect transporters other than GLT-1 and which affect kainate, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In hippocampal slices from postnatal day 14 mice lacking GLT-1, the current response of area CA1 pyramidal cells to superfused AMPA and NMDA (which are not taken up) was unaffected, whereas the response to 100 microm glutamate was more than doubled relative to that in wild-type littermates, a finding consistent with a decrease in glutamate uptake. In response to a few minutes of simulated ischaemia, pyramidal cells in wild-type mice showed a large and sudden inward glutamate-evoked current [the anoxic depolarization (AD) current], which declined to a less inward plateau. In mice lacking GLT-1, the time to the occurrence of the AD current, its amplitude, the size of the subsequent plateau current and the block of the plateau current by glutamate receptor blockers were all indistinguishable from those in wild-type mice. We conclude that GLT-1 does not contribute significantly to glutamate release or glutamate removal from the extracellular space in early simulated ischaemia. These data are consistent with glutamate release being by reversal of neuronal transporters, and with uptake into glia being compromised by the ischaemia-evoked fall in the level of ATP needed to convert glutamate into glutamine.

2-Amino-5-phosphonovalerate↗
PubMed2003

CPMG relaxation by diffusion with constant magnetic field gradient in a restricted geometry: numerical simulation and application.

Carr-Purcell-Meiboom-Gill (CPMG) measurements are the primary nuclear magnetic resonance (NMR) technique used for evaluating formation properties and reservoir fluid properties in the well logging industry and laboratory sample analysis. The estimation of bulk volume irreducible (BVI), permeability, and fluid type relies on the accurate interpretation of the spin-spin relaxation time (T(2)) distribution. The interpretation is complicated when spin's self-diffusion in an inhomogeneous field and restricted geometry becomes dominant. The combined effects of field gradient, diffusion, and a restricted geometry are not easily evaluated analytically. We used a numerical method to evaluate the dependence of the free and restricted diffusion on the system parameters in the absence of surface relaxation, which usually can be neglected for the non-wetting fluids (e.g., oil or gas). The parameter space that defines the relaxation process is reduced to two dimensionless groups: D* and tau*. Three relaxation regimes: free diffusion, localization, and motionally averaging regimes are identified in the (log(10)D*, log(10)tau*) domain. The hypothesis that the normalized magnetization, M*, relaxes as a single exponential with a constant dimensionless relaxation time T*(2) is justified for most regions of the parameter space. The numerical simulation results are compared with the analytical solutions from the contour plots of T*(2). The locations of the boundaries between different relaxation regimes, derived from equalizing length scales, are challenged by observed discrepancies between numerical and analytical solutions. After adjustment of boundaries by equalizing T*(2), numerical simulation result and analytical solution match each other for every relaxation regime. The parameters, fluid diffusivity and pore length, can be estimated from analytical solutions in the free diffusion and motionally averaging regimes, respectively. Estimation of the parameters near the boundaries of the regimes may require numerical simulation.

Journal Article↗
PubMed2003

Fast protein structure prediction using Monte Carlo simulations with modal moves.

Using normal modes to generate torsion space moves in Monte Carlo simulations of peptides and proteins is not a new idea; nevertheless, despite its power it has not received widespread application. We show that such a "Modal Monte Carlo" approach is an efficient tool for ab initio predictions of small-protein structures. We apply this method to the Trp cage, a 20-residue polypeptide designed to fold rapidly into a structure that includes tertiary contacts, despite its short length. We achieve a high-quality ab initio structure prediction in about 2 orders of magnitude less computation time than state of the art molecular dynamics techniques.

Computer Simulation↗
PubMed2005

Animal surgery during spaceflight on the Neurolab Shuttle mission.

INTRODUCTION: A surgical procedure has never been required or performed on a human in space. Parabolic microgravity simulations have suggested that surgery would be technically feasible during spaceflight. PROCEDURES: Survival surgery was performed for the first time on rats during the STS-90 Neurolab Shuttle mission. Craniotomy, leg dissection, thoracotomy, laminectomy, and laparotomy were performed as a part of physiological investigations. RESULTS: Surgical techniques successfully demonstrated in rats during spaceflight included general anesthesia, wound closure, wound healing, hemostasis, control of surgical fluids, operator restraint, and control of surgical instruments. No decrement in manual dexterity was noted by the crew, although operative time was longer compared with ground experience due to the need to maintain restraint of surgical supplies and instruments. CONCLUSIONS: The demonstration that technically demanding dissections could be accomplished successfully in space on rats suggests that comparable complex surgical procedures should be feasible on humans, if necessary, on future long-duration missions.

Aerospace Medicine↗
PubMedDate not supplied

In vivo bone mineral studies on volunteers during a 370-day antiorthostatic hypokinesia test.

Bone mineral of spine, femur, tibia, forearm, calcaneus, hand, and foot was studied on nine volunteers by quantitative computed tomography, neutron activation analysis, single and dual photon absorptiometry during and after long-term hypokinesia. Conditions of long-term space flight were simulated using a 370-day antiorthostatic hypokinesia test. It is shown that the highest mineral losses occur in foot bones including calcaneus. Remedial measures undertaken delay the process of osteoporosis development but do not completely exclude it. The results obtained by different methods are often conflicting. Consequently, the accuracy of the in vivo methods for bone mineral determination must be more thoroughly studied.

Absorptiometry, Photon↗
PubMed1997

Changes of the inner time structures in the sequences of interspike intervals produced by the activity of excitatory and inhibitory synapses: simulation with Gaussian input processes.

The computer simulation of space-temporal summation of post-synaptic potentials of neurone's membrane demonstrated the outstanding changes in the inner time structures of generated interspike intervals. The output time series of ISIs were studied using non-standard kind of time analysis -- recurrence plot method. Using this technique we observed phenomenon of unification in inner time structures of output series. Further we identified such parameters of model which exerted the most considerable influence on this phenomenon.

Action Potentials↗
PubMed1977

Optic disc edema in raised intracranial pressure. I. Evolution and resolution.

Progressively growing intracranial space-taking lesions were simulated in 32 rhesus monkeys by balloons introduced into the subarachnoid space of the temporal region. Optic disc edema (ODE) first appeared at the lower pole, then the upper pole, then the nasal part, and last the temporal part of the disc; severity of edema generally followed sult, most severe at the lower pole (P less than .005). Fluorescein fundus angiography showed that swelling of the optic disc preceded the vascular changes associated with ODE. Raised intracranial pressure for 24 hours, or less, could cause ODE. The atrophic part of the optic disc did not develop ODE. The studies indicate that swelling of the optic disc is the first sign of raised intracranial pressure and is due to swelling of the nerve fibers in the optic disc; the various associated vascular changes are secondary.

Animals↗
PubMed1999

Exploring the dynamic information content of a protein NMR structure: comparison of a molecular dynamics simulation with the NMR and X-ray structures of Escherichia coli ribonuclease HI.

The multiconformer nature of solution nuclear magnetic resonance (NMR) structures of proteins results from the effects of intramolecular dynamics, spin diffusion and an uneven distribution of structural restraints throughout the molecule. A delineation of the former from the latter two contributions is attempted in this work for an ensemble of 15 NMR structures of the protein Escherichia coli ribonuclease HI (RNase HI). Exploration of the dynamic information content of the NMR ensemble is carried out through correlation with data from two crystal structures and a 1.7-ns molecular dynamics (MD) trajectory of RNase HI in explicit solvent. Assessment of the consistency of the crystal and mean MD structures with nuclear Overhauser effect (NOE) data showed that the NMR ensemble is overall more compatible with the high-resolution (1.48 A) crystal structure than with either the lower-resolution (2.05 A) crystal structure or the MD simulation. Furthermore, the NMR ensemble is found to span more conformational space than the MD simulation for both the backbone and the sidechains of RNase HI. Nonetheless, the backbone conformational variability of both the NMR ensemble and the simulation is especially consistent with NMR relaxation measurements of two loop regions that are putative sites of substrate recognition. Plausible side-chain dynamic information is extracted from the NMR ensemble on the basis of (i) rotamericity and syn-pentane character of variable torsion angles, (ii) comparison of the magnitude of atomic mean-square fluctuations (msf) with those deduced from crystallographic thermal factors, and (iii) comparison of torsion angle conformational behavior in the NMR ensemble and the simulation. Several heterogeneous torsion angles, while adopting non-rotameric/syn-pentane conformations in the NMR ensemble, exist in a unique conformation in the simulation and display low X-ray thermal factors. These torsions are identified as sites whose variability is likely to be an artifact of the NMR structure determination procedure. A number of other torsions show a close correspondence between the conformations sampled in the NMR and MD ensembles, as well as significant correlations among crystallographic thermal factors and atomic msf calculated from the NMR ensemble and the simulation. These results indicate that a significant amount of dynamic information is contained in the NMR ensemble. The relevance of the present findings for the biological function of RNase HI, protein recognition studies, and previous investigations of the motional content of protein NMR structures are discussed.

Cluster Analysis↗
PubMed1999

The scale-invariant spatial clustering of leukemia in San Francisco.

This study tests the hypothesis of scale-invariant self-similar clustering of childhood leukemia cases over the San Francisco spatial area. The spatial distribution of leukemia cases has been investigated over seven scales of observation. A power-law relation of the variance to the mean of aggregates (quadrats) was used to detect possible scale-invariant self-similar clustering. The spatial distribution of leukemia cases (incidence from 1946 to 1964) was well fitted by a power-law function. The follow-up of clustering from the first years of case notification (1946) confirmed a scale-invariant self-similar spatial pattern with a stable power-law slope from 1952 onward. This pattern was shown to pertain specifically to school-age leukemia cases. Younger cases had a random distributional pattern over space. Observation and simulations of the distributional patterns revealed memory-keeping of historical (the pre-1953 era) fractal-like conditions. Based on a comparison of the leukemia fractal dimension with that of the city residential data, it is speculated that the current scale-invariant self-similar spatial clustering of the leukemia cases reflects the onset of the historical fractal patterning of the city residences at a particular time point in the past.

Child↗
PubMed2000

Mode of action of plasmolysed yeast on lymphocytes under microgravity stress.

A newly developed device to simulate microgravity for space biological investigations under laboratory conditions allowed us to apply a reproducible environmental stress on immunologically active cells. Cell proliferation, soluble IL-2 receptor in the culture supernatant, lymphocyte surface activation markers like CD25 (IL-2R), CD69 and HLA-Dr were the endpoints measured. Untreated donor lymphocyte reactions under microgravity were compared to the same cells treated with an immunomodulator from herbal plasmolysed yeast (Bio-Strath Food Supplement). The main finding is the enhancement of the proliferation inhibition under microgravitational stress by the herbal plasmolysed yeast.

Adjuvants, Immunologic↗
PubMed1997

Orthostatic tests after a 4-day confinement or simulated weightlessness.

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6 degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower-body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D-1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT and LBNP without difference between D-1 and R1. This experiment showed that a 4-day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.

Adult↗
PubMed2000

An in vitro comparison of 5 techniques for impressing dowel space preparations.

PURPOSE: This in vitro study compared 5 different dowel space impression techniques using polyvinyl siloxane impression material to determine which method produced fewer voids in the dowel space impression. MATERIALS AND METHODS: Five techniques were used to make impressions of a prepared dowel space in a simulated endodontically treated tooth. Technique I used a 25-gauge anesthetic needle to act as a vent at the apex of the preparation to reduce voids produced during the expression of light body impression material. The anesthetic needle was removed after the impression material was injected, and an impression post was then inserted to the depth of the preparation. Twenty impressions made using this technique were compared with other techniques that used the vent without a post, no vent with a post, no vent without a post, and a lentulo spiral with a post (Techniques II through V, respectively). The percentage of impressions with voids from each group was compared to determine which technique consistently produced a void-free impression of the complete preparation length. If voids were observed in the impression, the specimen was considered inadequate. RESULTS: The percents of void-free impressions using Techniques I through V were 100%, 70%, 40%, 60%, and 20%, respectively. CONCLUSIONS: Using a 25-gauge needle as a vent while expressing impression material into the dowel space followed by placing the impression post consistently produced void-free dowel space impressions.

Dental Impression Materials↗
PubMed1987

Ceftazidime and amikacin alone and in combination against Pseudomonas aeruginosa and Enterobacteriaceae.

The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites. Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter freundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers. Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg) for pseudomonads every 6 hr for 16 doses. Amikacin alone was ineffective for all 12 strains. Ceftazidime alone was successful (greater than or equal to 5.5 log10 colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads. Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads. The best in vitro tests for the prediction of in vivo outcome were high inoculum (greater than or equal to 7 log10 CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo.

Amikacin↗
PubMed1999

The role of a conserved proline residue in mediating conformational changes associated with voltage gating of Cx32 gap junctions.

We have explored the role of a proline residue located at position 87 in the second transmembrane segment (TM2) of gap junctions in the mechanism of voltage-dependent gating of connexin32 (Cx32). Substitution of this proline (denoted Cx32P87) with residues G, A, or V affects channel function in a progressive manner consistent with the expectation that a proline kink (PK) motif exists in the second transmembrane segment (TM2) of this connexin. Mutations of the preceding threonine residue T86 to S, A, C, V, N, or L shift the conductance-voltage relation of wild-type Cx32, such that the mutated channels close at smaller transjunctional voltages. The observed shift in voltage dependence is consistent with a reduction in the open probability of the mutant hemichannels at a transjunctional voltage (Vj) of 0 mV. In both cases in which kinetics were examined, the time constants for reaching steady state were faster for T86N and T86A than for wild type at comparable voltages, suggesting that the T86 mutations cause the energetic destabilization of the open state relative to the other states of the channel protein. The structural underpinnings of the observed effects were explored with Monte Carlo simulations. The conformational space of TM2 helices was found to differ for the T86A, V, N, and L mutants, which produce a less bent helix ( approximately 20 degrees bend angle) compared to the wild type, which has a approximately 37 degrees bend angle. The greater bend angle of the wild-type helix reflects the propensity of the T86 residue to hydrogen bond with the backbone carbonyl of amino acid residue I82. The relative differences in propensity for hydrogen bonding of the mutants relative to the wild-type threonine residue in the constructs we studied (T86A, V, N, L, S, and C) correlate with the shift in the conductance-voltage relation observed for T86 mutations. The data are consistent with a structural model in which the open conformation of the Cx32 channel corresponds to a more bent TM2 helix, and the closed conformation corresponds to a less bent helix. We propose that the modulation of the hydrogen-bonding potential of the T86 residue alters the bend angle of the PK motif and mediates conformational changes between open and closed channel states.

Animals↗
PubMed1998

Sensitivity analysis of a model of mammalian neural membrane.

The sensitivity of the strength-duration (S-D) relationship to changes in the parameters describing the sodium channel of mammalian neuronal membrane was determined by computer simulation. A space-clamped patch of neuronal membrane was modeled by a parallel nonlinear sodium conductance, linear leakage conductance, and membrane capacitance. Each parameter that governs the activation (m) and inactivation (h) variables of the sodium channel was varied from -50% to +50% of its default value, and for each variation a S-D relationship was generated. Individual changes in six of the eleven parameters (alpha mA, alpha mD, alpha hA, beta mA, beta mB, and beta hB) generated substantial changes in the rheobase current and chronaxie time (Tch) of the model. Changing the parameter values individually did not correct for the model's failure to generate excitation after the release from a long duration hyperpolarization (anode break excitation). Scaling a combination of five parameters (alpha mA, alpha mB, alpha hA, beta mA, and beta hB) by an equal amount produced a model that generated anode break excitation and increased Tch, but also decreased the amplitude of the action potential. To reproduce the amplitude of the action potential, the maximum sodium conductance and sodium Nernst potential were increased. These modifications generated a model that had S-D properties closer to experimental results, could produce anode break excitation, and reproduced the action potential amplitude.

Action Potentials↗
PubMed2001

[The assessment of the risk of altitude decompression sickness during simulation of repeated (with 12 hour interval) exits into open space].

Purpose of the investigation was to assess contribution of repeated (with a 12-hr interval) decompression to the risk of altitude decompression sickness (ADS) by simulation of 6-hr extravehicular activities (EVA) of space crewmembers in altitude chamber. The protocol included "ascents" of 6 essentially healthy male subjects at the age of 24 to 51 to the altitude of 7,600 m (37 kPa) following 30-min prebreathing (elimination of nitrogen from the body by breathing pure oxygen through a mask at the ambient pressure of 73 kPa = 2,600 m). Each subject participated in 2 experimental exposures: first initial and then repeated decompression. None of 24 "ascents" produced clinical signs of ADS. Comparison of the data concerning frequency and time points of detection by ultrasonic Doppler equipment of gas bubbles (GB) in the venous bed during decompression with initial, maximal and mean values of US signal intensity failed to state a significant difference between them. Data of the investigation were confronted with anticipated length of GB dispersion in body tissues.

Adult↗
PubMed1990

Drosophila segmentation: supercomputer simulation of prepattern hierarchy.

Spontaneous prepattern formation in a two level hierarchy of reaction-diffusion systems is simulated in three space co-ordinates and time, mimicking gap gene and primary pair-rule gene expression. The model rests on the idea of Turing systems of the second kind, in which one prepattern generates position dependent rate constants for a subsequent reaction-diffusion system. Maternal genes are assumed responsible for setting up gradients from the anterior and posterior ends, one of which is needed to stabilize a double period prepattern suggested to underly the read out of the gap genes. The resulting double period pattern in turn stabilizes the next prepattern in the hierarchy, which has a short wavelength with many characteristics of the stripes seen in actual primary pair-rule gene expression. Without such hierarchical stabilization, reaction-diffusion mechanisms yield highly patchy short wave length patterns, and thus unreliable stripes. The model yields seven stable stripes located in the middle of the embryo, with the potential for additional expression near the poles, as observed experimentally. The model does not rely on specific chemical reaction kinetics, rather the effect is general to many such kinetic schemes. This makes it robust to parameter changes, and it has good potential for adapting to size and shape changes as well. The study thus suggests that the crucial organizing principle in early Drosophila embryogenesis is based on global field mechanisms, not on particular local interactions.

Animals↗
PubMed2003

High order accurate, one-sided finite-difference approximations to concentration gradients at the boundaries, for the simulation of electrochemical reaction-diffusion problems in one-dimensional space geometry.

Accurate calculation of concentration gradients at the boundaries is crucial in electrochemical kinetic simulations, owing to the frequent occurrence of gradient-dependent boundary conditions, and the importance of the gradient-dependent electric current. By using the information about higher spatial derivatives of the concentrations, contained in the time-dependent, kinetic reaction-diffusion partial differential equation(s) in one-dimensional space geometry, under appropriate assumptions it is possible to increase the accuracy orders of the conventional, one-sided n-point finite-difference formulae for the concentration gradients at the boundaries, without increasing n. In this way a new class of high order accurate gradient approximations is derived, and tested in simulations of potential-step chronoamperometric and current-step chronopotentiometric transients for the Reinert-Berg system. The new formulae possess advantages over the conventional gradient approximations. For example, they allow one to obtain a third order accuracy by using two space points only, or fourth order accuracy by using three points, and yet they yield smaller errors than the conventional four-point, or five-point formulae, respectively. Needing fewer points, for approximating the gradients with a given accuracy, simplifies also the solution of the linear algebraic equations arising from the application of implicit time integration schemes.

Journal Article↗