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Effect of doublet impulse sequences on the transient and steady responses in the computer-simulated nerve cell.

The effects of doublet impulse sequences of the excitatory axon on the output response as firing probability (pr.) in the computer-simulated nerve cell were examined. A simple model was formulated to simulate the nerve cell, including the property that the resetting potential is influenced by the final membrane potential in the previous stage before firing. The relationship between input sequences with alternating long and short interval at the same mean rate and the transient and steady responses of the nerve cell was investigated. In this simulation, three summarized results were obtained: i) The responses were very sensitive to changing small size of excitatory post-synaptic potential (EPSP), especially in the firing stage of the transient state. ii) In the transient state, the size of characteristic area of responses was depending upon the size of absolute refractory period (ARP). The rise for shorter intervals was faster than that for longer intervals, agreeing well with part of the experimental results from the crayfish claw opener muscles. The transient responses were almost finished before the fifth firing. iii) In the steady state, the doublet impulse sequences usually produced the minimum response or valley-like response at which the doublet interval Td was 20 and/or 25 ms. These effects related to the characteristic areas in the transient responses.

Computers↗

Computer simulation of plasma insulin and glucose dynamics after subcutaneous insulin injection.

We developed a computer program for the simulation of plasma insulin and glucose dynamics after subcutaneous injection of insulin. The program incorporates a pharmacokinetic model to calculate the time courses of plasma insulin for various combinations of popular preparations (regular, NPH, lente, and ultralente). With the use of a pharmacodynamic model describing the dependence of glucose dynamics on plasma insulin and glucose levels, the program can predict the expected time course of plasma glucose in response to a change in carbohydrate intake, insulin dose, timing, or regimen. A set of typical parameters has been obtained by analysis of data from the literature. The results of several computer simulations are presented showing the effect on a 24-h insulin and glucose profile of systematically changing insulin regimen, dose, timing of meals, or timing of preprandial insulin administration. The program can be used to explore on a theoretical basis the impact of various factors associated with glycemic control in insulin-dependent diabetes mellitus. As an educational tool, the program provides a realistic environment for demonstration of the combined or isolated effects of insulin and diet on glycemia.

Absorption↗

Lymph flow characteristics and microvascular exchange: an analog computer simulation.

Lymphatic flow characteristics, which include both progressive lymphatic blockage and plateau of lymph flow with increasing interstitial fluid volume, were incorporated into an analog computer simulation of microvascular exchange, and their effects on interstitial fluid volume and protein content were investigated. The steady state and transient response of the microcirculation to changes in the properties of the lymph flow system are reported. The interstitial fluid and protein content is investigated as a function of venous pressure and for changes associated with the lymph flow characteristics. The interstitial protein content is generally more sensitive to changes in the lymph flow properties than is interstitial fluid volume. Properties of lymphatic drainage of tissues as they effect microvascular exchange are discussed.

Computers↗

A dual-frequency applied potential tomography technique: computer simulations.

Applied potential tomography has been discussed in relation to both static and dynamic imaging. We have investigated the feasibility of obtaining static images by measuring profiles at two frequencies of drive current to exploit the differing gradients of electrical conductivity with frequency for different tissues. This method has the advantages that no profile for the homogeneous medium is then needed, and the electrodes can be coupled directly to the skin. To demonstrate the principle, computer simulations have been carried out using published electrical parameters for mammalian tissues at frequencies of 100 and 150 kHz. The distribution of complex electric potentials was calculated by the successive over-relaxation method in two dimensions for an abdominal cross-section with 16 electrodes equally spaced around the surface. From the computed electrode potentials, images were reconstructed using a back-projection method (neglecting phase information). Liver and kidney appeared most distinctly on the image because of their comparatively large conductivity gradients. The perturbations in the electrode potential differences between the two frequencies had a mean value of 5%, requiring accurate measurement in a practical system, compared with 150% when the 100 kHz values were related to a simulation of homogeneous saline equal in conductivity to muscle. The perturbations could be increased by widening the separation of the frequencies. Static imaging using a dual-frequency technique appears to be feasible, but a more detailed consideration of the electrical properties of tissues is needed to determine the optimum choice of frequencies.

Computer Simulation↗

[Computer simulation of a patient with gastrointestinal symptoms used for evaluation of clinical decision among general practitioners].

This study used a computer-based simulation of a patient with gastrointestinal symptoms for an investigation of decision-making amongst 122 general practitioners participating in the 6th Nordic Congress of General Practice. The simulation model, developed in the computer software COMCATS, makes use of an IBM-compatible personal computer attached to an automated slide-projector. All participants were given a short introduction to the patient and his symptoms, but all further information was optimal and selected by the doctor. Large variations were found between the participants with respect to clinical patterns: for example, expenses for further examinations ranged from 0 to 2,400 Danish crowns. For research into clinical decision-making the great advantages of the computer-model are that it allows for a standardisation of the clinical situation, gives the doctor an opportunity to select between optional information and permits an automatic gathering of huge amounts of information about the decision-making process.

Adult↗

Thyroid homeostasis as studied by computer simulation.

Physico-chemical factors alone may account for much of the thyroid gland homeostasis and by inference for homeostasis of basal energy metabolism in mammals. Computer simulations indicate that changes of several of the important rate constants for thyroid function have little effect on circulating thyroid hormone concentrations. This was especially true of the rate constants for thyroid hormone release from the thyroid gland and to a lesser extent of the rate constants governing thyroid hormone metabolism and excretion. The rate at which thyroid hormone levels in blood respond to changes was rather slow indicating that transient changes in dietary iodine or in the rate constants governing thyroid function would have little effect. If changes taking place over several days, such as during the initiation of lactation, the parameters of thyroid function change at a corresponding rate.

Animals↗

Mathematical modeling and computer simulation of isoelectric focusing with electrochemically defined ampholytes.

A mathematical model of isoelectric focusing at the steady state has been developed for an M-component system of electrochemically defined ampholytes. The model is formulated from fundamental principles describing the components' chemical equilibria, mass transfer resulting from diffusion and electromigration, and electroneutrality. The model consists of ordinary differential equations coupled with a system of algebraic equations. The model is implemented on a digital computer using FORTRAN-based simulation software. Computer simulation data are presented for several two-component systems showing the effects of varying the isoelectric points and dissociation constants of the constituents.

Journal Article↗

Towards 3-D modelling of epithelia by computer simulation.

The present work is a preliminary step towards dynamic 3-D modelling by computer graphics simulation of the structure of normal and pathological epithelia, using an expert system. In its present state, Esexsy (Epithelium Simulation by EXpert SYstem) allows the construction, through iterative steps, of a simple 3-D representation of the nasal epithelium, based on the positions, sizes and shapes of nuclei. The iterative process is based on statistical comparisons between distributions of parameter values calculated from real (2-D) histological sections and those issued from an equivalent computer 'section' through the simulated 3-D image. We show the results of attempts at simulating normal, metaplastic and dysplastic states of the nasal epithelium, the latter two being characterized by a progressive architectural disorganization, accompanied by nuclear size/shape alterations. The representation takes into account the size, shape, orientation and spatial arrangement of nuclei, with one or several layers from the basal lamina to the lumen. A modified Poisson point process is used at present to position the nuclei, which are modelled by bi-axial spheroids (from prolate to oblate through spherical), with random orientation and size/shape deviations. It should be possible to use the same computer program to simulate other types of epithelia and to achieve increasingly realistic representations by incorporating, notably, nuclear deformations and chromatin texture.

Computer Graphics↗

The cause of the shorter gestation length for twin calves: A computer simulation.

The possibility that the shorter length of gestation for twin calves is because pregnancy is determined by the earlier maturing twin has been investigated by computer simulation. The simulation indicated that this explanation alone could account for only about half the shortening of gestation for natural twin calves, and it is suggested that the combined actions of both twins is superimposed on the stimulus of the earlier maturing twin to initiate parturition. With mixed-species twins produced by embryo transfer, the immaturity of the more slowly maturing Bos indicus is such that it cannot cooperate with the earlier maturing Bos taurus cotwin to shorten gestation to appreciably less than is normal for single Bos taurus pregancies.

Journal Article↗

Theoretical analysis and computer simulation of fluorescence lifetime measurements. II. Contour length dependence of single polymers.

Fluorescence lifetime measurements in a polymer chain are modeled using a memory function expansion, computer simulations, and simple scaling arguments. Unless the quenching rate is localized and infinitely fast, the fluorescence lifetime is generally not equivalent to the first passage time. The fluorescence lifetime distribution is decomposed into memory functions that can be measured separately in single-molecule experiments. The leading order of the expansion gives the Wilemski-Fixman (WF) approximation, and the convergence of higher order terms determines its validity. Simulations of the fluorescence quenching on a Rouse chain verify the accuracy of the WF approximation at small contact radii, short contour lengths, and small quenching rates. Detailed investigation of the average fluorescence lifetime reveals two competing mechanisms: the independent motion of end-to-end vector, which dominates at small contact radius, and the slowest relaxation of polymer, which dominates at large contact radius. The Wilemski-Fixman rate is used in combination with scaling arguments to predict the dependence of fluorescence lifetime on the contour length. Our predictions for the scaling of the average lifetime with the contour length are in good agreement with both simulations and recent experiments by Eaton and his group [L. J. Lapidus, W. A. Eaton, and J. Hofrichter, Proc. Natl. Acad. Sci. U.S.A. 97, 7220 (2000)].

Journal Article↗

[Part I. Theory and computer simulation for cerebrospinal infusion].

A pharmacokinetic one-compartment model for the cerebrospinal infusion for the brain tumor chemotherapy is described together with various parameters used for computer simulation. An antitumor protein, neocarzinostatin (NCS) as a prototype drug, has been utilized since it was found effective against glioblastoma cells at extremely low concentration (less than 5 ng/ml) and it is readily inactivated by serum. A very slow infusion velocity was found necessary for an appropriate dose regimen; for example, 0.25mg of the drug should be infused into CSF for about 40 min to attain a drug level of 8 ng/ml.

Antibiotics, Antineoplastic↗

Optimization of background electrolytes for capillary electrophoresis: II. Computer simulation and comparison with experiments.

A mathematical and computational model described in the previous paper (Gas, B., Coufal, P., Jaros, M., Muzikár, J., Jelínek, L., J. Chromatogr. A 2001, 905, 269-279) is adapted, algorithmized, and a computer program PeakMaster having a status of freeware (http://natur.cuni.cz/ approximately gas) is introduced. The model enables optimization of background electrolyte (BGE) systems for capillary zone electrophoresis. The model allows putting to use uni- or di- or trivalent electrolytes and allows also for modeling highly acidic or alkaline BGEs. It takes into account the dependence of ionic mobilities and dissociation of weak electrolytes on the ionic strength. The model calculates the effective mobility of analytes and predicts parameters of the system that are experimentally available, such as the transfer ratio, which is a measure of the sensitivity in the indirect UV detection or the molar conductivity detection response, which expresses the sensitivity of the conductivity detection. Further, the model enables evaluation of a tendency of the analyte to undergo electromigration dispersion or peak broadening. The suitability of the model is verified by comparison of the predicted results with experiments, even under conditions that are far from ideal (under extreme pH and a high ionic strength).

Algorithms↗

Computer simulation for deconvolution of a heat conduction batch microcalorimeter by the D-B Finite Element Technique.

The method described here is a general numerical analysis procedure which has been applied to a heat conduction Batch calorimeter for the deconvolution of its thermograms, and is based on a computer simulation of the heat conduction behavior of the instrument with time. We show by means of test signals that the method can deconvolute the signal with a resolving time that is about two orders of magnitude smaller than the time constant of the calorimeter itself. The method can be applied to time signals generally, provided that the instrument producing them can be simulated.

Calorimetry↗

[Computer simulation of different types of evolutionary process].

The computer model of two alternative variants of biological evolution is proposed. The first variant supposes random while the second--directed change of individual features, thus corresponding to the Darwinian and non-Darwinian evolution. The evolution of fish communities in fresh waters serves as a particular example. The model is executed using object-oriented method of programming and mathematical apparatus of fuzzy logics. The investigation of the model showed that process of Darwinian evolution is connected with significantly greater species diversity and variability of evolutionary process trajectories than non-Darwinian one. On the other hand, non-Darwinian type of evolution provides fast achievement of high individual fitness, especially under conditions of constant environment. Non-Darwinian type evolution failed in big evolutionary alteration (for example, transition to predation); while the Darwinian evolution under the same conditions can produce such alterations though it took more time and many extinct species. Phylogenetic tree of Darwinian evolution is always more complex than of non-Darwinian one under the same conditions.

Animals↗

Anisotropic ordering in sheared binary fluids with viscous asymmetry: experiment and computer simulation.

Optical measurements of the structure and morphology of phase-separating polymer blend under simple shear flow have been performed and the results are compared with computer simulations of sheared phase-separating binary mixtures with viscous asymmetry in the fluid components. Information about the structure is obtained from the two-point composition correlation function. Both experiment and simulation suggest subtle differences in the shear response depending on whether the more viscous phase is dispersed or continuous. Measurements of the string width along the neutral direction suggest power-law decay in the shear rate with an exponent of 1/3 when the more viscous phase is dispersed. The simulations suggest that the mean string width, measured along the velocity-gradient direction in the two-dimensional model calculation, exhibits power-law decay in the shear rate with an exponent of 1/3 independent of which phase is dispersed.

Journal Article↗

Computer simulations of bent-core liquid crystals.

The phase behavior of model linear and bent-core molecules has been studied using isothermal-isobaric Monte Carlo computer simulations. The molecular model consists of seven Lennard-Jones spheres rigidly arranged in a "V" shape, with external bond angle, gamma. With gamma=0 degrees (linear molecules), we find isotropic, nematic, untilted smectic A, and two layered phases in which the molecules are tilted with respect to the layer normal. The latter two phases correspond to distinct branches in the equation of state, and possess different types of ordering within and between the layers; these phases are tentatively assigned as being smectic B and crystal. Apart from the possible existence of a tilted smectic B, the phase behavior of this system is broadly in line with earlier simulation studies on related linear molecular models. In the gamma=20 degrees system, isotropic, nematic, and tilted smectic- B phases are observed. Interestingly, the range of stability of the nematic phase is enhanced compared to the gamma=0 degrees system. In simulations of the gamma=40 degrees system, nematic phases are absent, and only isotropic and tilted phases are in evidence. The in-layer structure of the tilted phases shows a very clear change from smectic- B to smectic- A ordering upon increasing the temperature. In all instances of a tilted phase, the degree of molecular tilt is in the region of 30+/-5 degrees, with respect to the smectic layer normal, which corresponds closely to typical experimental observations in real bent-core liquid crystals. In our model, the tilt provides efficient packing of the spheres and favorable attractive interactions between molecules. The relevance of the present simulation model to real bent-core liquid crystals is discussed critically.

Journal Article↗

Netropsin binding to poly[d(IC)].poly[IC)] and poly[d(GC].poly[d(GC)]: a computer simulation.

The thermodynamic cycle perturbation approach has been used to calculate the difference in the free energy of binding of netropsin to two different DNA molecules. In the computer simulations, all the inosine residues have been gradually 'mutated' into guanosine in a DNA dodecamer and in a complex of the same dodecamer with netropsin. The difference in binding free energy of about 4.3 kcal mol-1 agrees well with the experimentally determined value of 4.0 kcal mol-1. One structural determinant of the specificity seems to be the width of the minor groove in the two complexes.

Guanidines↗