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At least 1,009 records · Page 56Linked to original sources
PubMedDate not supplied

Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest.

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4 +/- 1.9 years) participated twice in a 7-day HDBR--one time with thigh cuffs (worn daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at -15, -30, -45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: -5.85 +/- 0.95%; WTC: -9.09 +/- 0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1 +/- 1.3 min; WTC 7.0 +/- 1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.

Adult↗
PubMed2003

Optimal stochastic correction strategies for rigid-body target motion.

PURPOSE: To derive optimal correction strategies for setup errors, including the uncertainty in their measurement, and to analyze their impact on treatment margins. METHODS AND MATERIALS: New concepts like image-guided radiotherapy aim to provide an increasing amount of targeting information during treatment. Future treatment devices incorporating imaging capabilities will facilitate frequent correction of treatment setup errors. It is, therefore, possible to design new correction protocols that reduce not only systematic but also random setup errors. A novel, very general approach to developing optimal correction strategies in the presence of measurement uncertainties is derived from linear systems theory. In the simplest approach, the state variable of the system, which represents the patient, is the spatial displacement of the center-of-mass of the clinical target volume with respect to the planning CT. This displacement is the sum of a systematic and a random component. Uncertainties in the measured value of the state variable due to the measurement process, image processing technique, or organ deformation are naturally incorporated into a linear system. The true value of the displacement can be estimated from the noisy measurements with a stochastic filter (Kalman filter). These estimates provide an optimal control law for the system and therefore optimal values for the setup corrections. In the case of unknown systematic and random error variances, an adaptive version of the filter was implemented. The statistical properties of the filter were investigated by performing simulations of the state space model and assessed for individual patients and a large patient population subject to different action criteria. RESULTS: Over a patient population, the corrections by the Kalman filter estimates are always advantageous compared with the corrections by the measured values themselves. For a small percentage of individual patients, however, the Kalman corrections worsen the results. For large measurement error, the residual standard deviation of the random setup errors can be reduced by approximately 28% for over 90% of the patients. The uncertainty in the measured value impairs the ability to completely account for uncertainties. CONCLUSIONS: The Kalman estimates provide an effective means to perform daily setup corrections in the presence of measurement errors. The linear system approach is very versatile and can be extended to more general state variables.

Algorithms↗
PubMed2000

A structural model of the orthorhombic Ga7Mn5 derived from its HREM image

The base-centered orthorhombic approximant Ga7Mn5 (a = 4.547(6) nm, b = 1.256(9) nm, c = 1.482(1) nm) consisting of flattened hexagon and concave octagon (called "crown" in this paper) subunits shown by high-resolution electron microscopy (HREM) was found to coexist with the Ga-Mn decagonal quasicrystal in the Ga58Mn42 alloy. The atomic sites in the flattened hexagon subunit have been deduced recently from a structural study of the orthorhombic Ga-Mn (1/1,1/1) approximant that consists only of the hexagon subunits. Similarly, the atomic sites in the crown subunit have been deduced from another orthorhombic Ga-Mn (2/1,1/1) approximant consisting only of the crown subunits. A structural model of the orthorhombic Ga7Mn5 can thus be constructed from these structural subunits. There are 332 Ga atoms and 232 Mn atoms in a unit cell, with a composition of Mn41.2Ga58.8, satisfying the symmetry of the space group Bmm2. The simulated electron diffraction patterns, [010] HREM images, and X-ray powder diffraction pattern based on this structural model agrees mainly with the experimental observations.

Journal Article↗
PubMed2005

Emission factors and importance of PCDD/Fs, PCBs, PCNs, PAHs and PM10 from the domestic burning of coal and wood in the U.K.

This paper presents emission factors (EFs) derived for a range of persistent organic pollutants (POPs) when coal and wood were subject to controlled burning experiments, designed to simulate domestic burning for space heating. A wide range of POPs were emitted, with emissions from coal being higher than those from wood. Highest EFs were obtained for particulate matter, PM10, (approximately 10 g/kg fuel) and polycyclic aromatic hydrocarbons (approximately 100 mg/ kg fuel for sigmaPAHs). For chlorinated compounds, EFs were highest for polychlorinated biphenyls (PCBs), with polychlorinated naphthalenes (PCNs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) being less abundant. EFs were on the order of 1000 ng/kg fuel for sigmaPCBs, 100s ng/ kg fuel for sigmaPCNs and 100 ng/kg fuel for sigmaPCDD/Fs. The study confirmed that mono- to trichlorinated dibenzofurans, Cl1,2,3DFs, were strong indicators of low temperature combustion processes, such as the domestic burning of coal and wood. It is concluded that numerous PCB and PCN congeners are routinely formed during the combustion of solid fuels. However, their combined emissions from the domestic burning of coal and wood would contribute only a few percent to annual U.K. emission estimates. Emissions of PAHs and PM10 were major contributors to U.K. national emission inventories. Major emissions were found from the domestic burning for Cl1,2,3DFs, while the contribution of PCDD/F-sigmaTEQ to total U.K. emissions was minor.

Air Pollutants↗
PubMed2001

Hydration of the calcium ion. An EXAFS, large-angle x-ray scattering, and molecular dynamics simulation study.

The structure of the hydrated calcium(II) ion in aqueous solution has been studied by means of extended X-ray absorption fine structure spectroscopy (EXAFS), large-angle X-ray scattering (LAXS), and molecular dynamics (MD) methods. The EXAFS data displayed a broad and asymmetric distribution of the Ca-O bond distances with the centroid at 2.46(2) A. LAXS studies on four aqueous calcium halide solutions (1.5-2 mol dm(-)(3)) gave a mean Ca-O bond distance of 2.46(1) A. This is consistent with a hydration number of 8 determined from correlations between mean distances and coordination numbers from crystal structures. The LAXS studies showed a second coordination sphere with a mean Ca.O(II) distance of 4.58(5) A, and for the hydrated halide ions the distances Cl.O 3.25(1) A, Br.O 3.36(1) A, and I.O 3.61(1) A were obtained. Molecular dynamics simulations of CaCl(2)(aq) were performed using three different Ca(2+)-OH(2) pair potentials. The potential from the GROMOS program gave results in agreement with experiments, i.e., a coordination number of 8 and an average Ca-O distance of 2.46 A, and was used for further comparisons. Theoretical EXAFS oscillations were computed for individual MD snapshots and showed very large variations, though the simulated average spectrum from 2000 snapshots gave satisfactory agreement with the experimental EXAFS spectra. The effect of thermal motions of the coordinated atoms is inherent in the MD simulation method. Thermal disorder parameters evaluated from simulated spatial atom distribution functions of the oxygen atoms coordinated to the calcium ion were in close agreement with those from the current LAXS and EXAFS analyses. The combined results are consistent with a root-mean-square displacement from the mean Ca-O distance of 0.09(2) A in aqueous solution at 300 K.

Body Water↗
PubMed2002

Novel inorganic frameworks constructed from double-four-ring (D4R) units: computational design, structures, and lattice energies of silicate, aluminophosphate, and gallophosphate candidates.

The design of new and interesting inorganic frameworks is an ongoing challenge in materials sciences. New structures containing double-four-ring (D4R) units have recently received particular attention. The present work focuses on the computational design of new three-dimensional frameworks made of D4R units exclusively. In a first step, our simulations explore the possible ways to assemble predefined D4R units in 3D space using a sophisticated cascade of simulated annealing/minimizations steps (autoassembly of secondary building units method). While the existing zeotype topologies were successfully generated, new topologies were predicted including very open frameworks containing new types of cages. In a second step, lattice energy minimizations were performed to estimate the viability of these hypothetical frameworks as silicate, aluminophosphaste, and gallophosphate candidates. When comparing the hypothetical structures to existing compounds, our results raise the challenging question of the appropriate chemical composition that should be aimed at for a given framework topology of interest.

Journal Article↗
PubMed2004

Stereochemistry of isoplagiochin C, a macrocyclic bisbibenzyl from liverworts.

Cyclic bisbibenzyls, like isoplagiochins C (1) and D (2), are stereochemically intriguing molecules: Although not equipped with any of the traditional stereogenic elements that render molecules conformationally stable per se, they are sometimes isolated in an optically active form and are thus chiral at room temperature. The paper describes quantum chemical calculations, in particular investigations of the conformational space and molecular dynamics simulations, showing that the helicity is a property of the entire molecule, whose ring strain makes the molecule configurationally stable overall, with (formally) three stereogenic elements (two biaryl axes and one helical stilbene unit). Only one of the biaryl axes (the 'upper' one, joining C-12' and C-14) has a stable configuration, leading to a population of four interconverting diastereomers, yet without racemization at room temperature. On the basis of these conformational and dynamic calculations, the circular dichroism spectrum of isoplagiochin C (1) was calculated, leading to the first assignment of the absolute configuration of a cyclic bisbibenzyl. Accordingly, 1 has the P-configuration at the stereochemically stable biaryl axis and constitutes a mixture of diastereomers with respect to the other biaryl axis and the helical stilbene unit. From the temperature dependence of the racemization rates, an enantiomerization barrier of 101.6 kJ/mol was determined. Likewise, for the first time for cyclic bisbibenzyls, the enantiomeric ratio of this natural product was determined, by chromatography on a chiral phase with CD-coupling. Accordingly, 1 from Plagiochila deflexa is not enantiomerically pure, but occurs in a 85:15 ratio in favor of the enantiomer that has the P-configuration at the stereochemically stable axis.

Bibenzyls↗
PubMed2004

How much backbone motion in ubiquitin is required to account for dipolar coupling data measured in multiple alignment media as assessed by independent cross-validation?

The magnitude of backbone internal motions in the small protein ubiquitin that needs to be invoked to account for dipolar coupling data measured in multiple alignment media is investigated using an intuitively straightforward approach. This involves simultaneous refinement of the coordinates (against NOE, torsion angle, and dipolar coupling restraints) and optimization of the magnitudes and orientations of the alignment tensors by means of torsion angle simulated annealing and Cartesian space minimization. We show that N-H dipolar couplings in 11 different alignment media and N-C', H(N)-C', and C alpha-C' dipolar coupling in two alignment media can be accounted for, at approximately the level of uncertainty in the experimental data, by a single structure representation. Extension to a two-member ensemble representation which provides the simplest description of anisotropic motions in the form of a two-site jump model (in which the overall calculated dipolar couplings are the averages of the calculated dipolar couplings of the individual ensemble members), results in modest, but significant, improvements in dipolar coupling R-factors for both the working set of couplings used in the refinement and for the free cross-validated set of C alpha-H alpha dipolar couplings recorded in two alignment media. Extensions to larger ensemble sizes do not result in any R-factor improvement for the cross-validated C alpha-H alpha dipolar couplings. With a few notable exceptions, the amplitudes of the anisotropic motions are small, with S(2)(jump) order parameters > or =0.8. Moreover, the structural impact of those few residues that do exhibit larger amplitude motions (S(2)(jump) ranging from 0.3 to 0.8) is minimal and can readily be accommodated by very small backbone atomic rms shifts (<0.5 A) because of compensatory changes in phi and psi backbone torsion angles. In addition, evidence for correlated motions of N-H bond vectors is observed. For most practical applications, however, refinement of NMR structures against dipolar couplings using a single structure representation is adequate and will not adversely impact coordinate accuracy within the limits of the NMR method.

Kinetics↗
PubMed1999

Pharmacokinetics of methotrexate in the extracellular fluid of brain C6-glioma after intravenous infusion in rats.

PURPOSE: Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. METHODS: Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. RESULTS: Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 +/- 5.3%. MTX concentrations in tumor ECF represented about 1-2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2alpha, t1/2beta, MRT, fb, Vd, and CL(T)), except for a 1.7-fold increase of AUC(Plasma) and a 3.8-fold increase in AUC(ECF), which resulted in a 2.3-fold increase in penetration (AUC(ECF)/AUC(Plasma)). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. CONCLUSIONS: High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.

Animals↗
PubMed2000

Electrolyte and pH dependence of heart rate during hemodialysis: a computer model analysis.

The influence of hemodialysis-induced modifications in extracellular fluid characteristics on heart rate was investigated by using a detailed computer model of sinus-node electrical activity. Changes similar to those occurring in the course of hemodialysis in extracellular concentrations of sodium (from 138 to 140 mM), potassium (from 6 to 3.3 mM), and calcium (from 1.2 to 1.5 mM) ions as well as in pH (from 7.31 to 7.4) and intracellular volume were simulated. The model predicted that such changes may largely influence the rhythm of the sinoatrial node pacemaker, causing the heart rate to range from 69 to 86 bpm. Heart rate increases after removing potassium (up to 7 bpm) and also after calcium perfusion (up to 11 bpm) whereas restoring pH slows heart beat (up to 6 bpm). Extracellular sodium has no significant influence, but the heart rate strictly depends on intracellular sodium concentration (5 bpm/mM). A complex dependence of heart rate on electrolytes and pH was also recognized. Providing extracellular potassium concentration is maintained above 5 mM, heart rate exhibits low sensitivity to changes in calcium and potassium. When potassium concentration is reduced below 4.5 mM, heart rate sensitivity to calcium and potassium increases significantly to 10 and 30 bpm/mM, respectively. A sustained increase in heart rate always corresponds to an increase in intracellular sodium concentration.

Acetylcholine↗
PubMed1995

Secondary cycle of equilibria in a system with cosymmetry, its creation by bifurcation and impossibility of symmetric treatment of it.

A study is reported of the bifurcation of a cycle of equilibria of an autonomous differential equation with cosymmetry in Hilbert space, which is a simulation of the problem of planar filtrational convection of a fluid in a porous medium. The Lyapunov-Schmidt method and perturbation theory are used to find its amplitude and the damping rate of the dominant mode. It is shown that, in the abstract general model, and also in the problem of convection in a rectangular container, this damping rate varies along the cycle of equilibria. Hence, the cycle of equilibria cannot be an orbit of the action of any symmetry group of the given system. (c) 1995 American Institute of Physics.

Journal Article↗
PubMed2006

A time correlation function theory describing static field enhanced third order optical effects at interfaces.

Sum vibrational frequency spectroscopy, a second order optical process, is interface specific in the dipole approximation. At charged interfaces, there exists a static field, and as a direct consequence, the experimentally detected signal is a combination of enhanced second and static field induced third order contributions. There is significant evidence in the literature of the importance/relative magnitude of this third order contribution, but no previous molecularly detailed approach existed to separately calculate the second and third order contributions. Thus, for the first time, a molecularly detailed time correlation function theory is derived here that allows for the second and third order contributions to sum frequency vibrational spectra to be individually determined. Further, a practical, molecular dynamics based, implementation procedure for the derived correlation functions that describe the third order phenomenon is also presented. This approach includes a novel generalization of point atomic polarizability models to calculate the hyperpolarizability of a molecular system. The full system hyperpolarizability appears in the time correlation functions responsible for third order contributions in the presence of a static field.

Computer Simulation↗
PubMedDate not supplied

Tetraethylammonium binding to the outer mouth of the KcsA potassium channel: implications for ion permeation.

Extracellular tetraethylammonium (TEA+) inhibits the current carried out by K+ ions in potassium channels. Structural models of wild-type (WT) and Y82C KcsA K+ channel/TEA+ complexes are here built using docking procedures, electrostatics calculations and molecular dynamics simulations. The calculations are based on the structure determined by Doyle et al. (11) Our calculations suggest that in WT, the TEA+ cation turns binds at the outer mouth of the selectivity filter, stabilized by electrostatic and hydrophobic interactions with the four Tyr82 side chains. Replacement of Tyr82 with Cys causes a decrease of the affinity of the cation for the channel, consistently with the available site-directed mutagenesis data (16). An MD simulation in which K+ replaces TEA+ provides evidence that TEA+ binding site can accommodate a potassium ion, in agreement with the high-resolution structure recently reported by Zhou et al. (20)

Bacterial Proteins↗
PubMed2001

Extracellular blockade of K(+) channels by TEA: results from molecular dynamics simulations of the KcsA channel.

TEA is a classical blocker of K(+) channels. From mutagenesis studies, it has been shown that external blockade by TEA is strongly dependent upon the presence of aromatic residue at Shaker position 449 which is located near the extracellular entrance to the pore (Heginbotham, L., and R. MacKinnon. 1992. Neuron. 8:483-491). The data suggest that TEA interacts simultaneously with the aromatic residues of the four monomers. The determination of the 3-D structure of the KcsA channel using X-ray crystallography (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69-77) has raised some issues that remain currently unresolved concerning the interpretation of these observations. In particular, the center of the Tyr82 side chains in KcsA (corresponding to position 449 in Shaker) forms a square of 11.8-A side, a distance which is too large to allow simultaneous interactions of a TEA molecule with the four aromatic side chains. In this paper, the external blockade by TEA is explored by molecular dynamics simulations of an atomic model of KcsA in an explicit phospholipid bilayer with aqueous salt solution. It is observed, in qualitative accord with the experimental results, that TEA is stable when bound to the external side of the wild-type KcsA channel (with Tyr82), but is unstable when bound to a mutant channel in which the tyrosine residue has been substituted by a threonine. The free energy profile of TEA relative to the pore is calculated using umbrella sampling simulations to characterize quantitatively the extracellular blockade. It is found, in remarkable agreement with the experiment, that the TEA is more stably bound by 2.3 kcal/mol to the channel with four tyrosine residues. In the case of the wild-type KcsA channel, TEA (which has the shape of a flattened oblate spheroid) acts as an ideal plug blocking the pore. In contrast, it is considerably more off-centered and tilted in the case of the mutant channel. The enhanced stability conferred by the tyrosine residues does not arise from Pi-cation interactions, but appears to be due to differences in the hydration structure of the TEA. Finally, it is shown that the experimentally observed voltage dependence of TEA block, which is traditionally interpreted in terms of the physical position of the TEA along the axis of the pore, must arise indirectly via coupling with the ions in the pore.

Bacterial Proteins↗
PubMed2003

Evaluation of an EIT reconstruction algorithm using finite difference human thorax models as phantoms.

A finite difference model of the human thorax with 113,400 control volumes (nodes) based on ECG gated MRI images was used to evaluate the Sheffield DAS-01P EIT system. Sixteen simulated electrode positions equally spaced around the thorax model at approximately the fourth intercostals space level were selected. Pairs of adjacent positions were excited sequentially by injecting current in a manner similar to that used by the Sheffield DAS-01P EIT system. The resulting voltages on the non-excited electrode positions were calculated and used to reconstruct the image using the Sheffield filtered back projection algorithm. By changing the resistivities of the lungs, the ventricles and the atria over a range of 1% to 40%, the resulting changes in the images were quantified by measuring the average resistivity change over a region defined automatically by two thresholds, 40% or 80% of the average of the first four pixels with the largest change. The results show that the changes observed in the images are consistently less than the changes in the model, but changed in a nearly linear manner as a function of resistivity in the model. For 40% resistivity changes in the model for right lung, right ventricle and right atrium, the observed resistivity changes in the region of interest (ROI, defined by the 80% threshold) of the images are 32% for the right lung, 11% for the right ventricle and 5.5% for the right atrium, which suggests strong volume dependence of EIT imaging. The effect of structural (size) change between end diastole and end systole was also studied, which showed large resistivity changes caused in the heart region of the constructed image. The study demonstrates that the Sheffield DAS-01P EIT reconstruction algorithm tracks the change occurring in the lungs most closely and with proper scaling may be used to observe physiological changes.

Algorithms↗
PubMed2004

DNA and its counterions: a molecular dynamics study.

The behaviour of mobile counterions, Na+ and K+, was analysed around a B-DNA double helix with the sequence CCATGCGCTGAC in aqueous solution during two 50 ns long molecular dynamics trajectories. The movement of both monovalent ions remains diffusive in the presence of DNA. Ions sample the complete space available during the simulation time, although individual ions sample only about one-third of the simulation box. Ions preferentially sample electronegative sites around DNA, but direct binding to DNA bases remains a rather rare event, with highest site occupancy values of <13%. The location of direct binding sites depends greatly on the nature of the counterion. While Na+ binding in both grooves is strongly sequence-dependent with the preferred binding site in the minor groove, K+ mainly visits the major groove and binds close to the centre of the oligomer. The electrostatic potential of an average DNA structure therefore cannot account for the ability of a site to bind a given cation; other factors must also play a role. An extensive analysis of the influence of counterions on DNA conformation showed no evidence of minor groove narrowing upon ion binding. A significant difference between the conformations of the double helix in the different simulations can be attributed to extensive alpha/gamma transitions in the phosphate backbone during the simulation with Na+. These transitions, with lifetimes over tens of nanoseconds, however, appear to be correlated with ion binding to phosphates. The ion-specific conformational properties of DNA, hitherto largely overlooked, may play an important role in DNA recognition and binding.

Binding Sites↗
PubMed1994

On the stability and plastic properties of the interior L3 loop in R. capsulatus porin. A molecular dynamics study.

Structural properties of Rhodobacter capsulatus porin are studied by molecular dynamics simulation using the GROMOS force field. Unconstrained simulations of the trimer and monomer show the trimer to be more stable than the isolated monomer. Simulations of the L3 loop inside the pore are used to assess its stability and plastic properties. Simulated annealing shows that the conformational space available to the L3 loop inside the pore is very large. Simulations at different temperatures show that the energy hypersurface around the open state is complex and flat. These studies also indicate four zones that are more flexible than the rest of the loop. Two of these are stabilized by the addition of the detergent molecule present in the X-ray structure. It is possible that the two remaining flexible zones, situated in the half of the loop facing the extracellular end of the porin molecule, residues Asp93-Gly98 and Arg110-Leu111, are involved in a mechanism for opening and closing of the pore.

Amino Acid Sequence↗
PubMed1987

Extrinsic causes of vesical filling defects on scintigraphy.

Three children are reported with vesical filling defects on scintigraphy secondary to extrinsic causes. In two chronically constipated individuals undergoing bone scintigraphy, the extrinsic pressure on the bladder by rectosigmoid feces resulted in simulation of intrinsic space-occupying lesions. Focal attenuation of bladder activity on nuclear cystography by the metal distal hook of a Harrington rod also produced the pseudo-appearance of a vesical filling defect in a third patient.

Adolescent↗