[Bicameral diffusion model of a synapse].
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The pharmacokinetics of ciprofloxacin in plasma and lung tissue at steady-state (500 mg b.i.d.) were studied in 38 patients subjected to lung surgery for bronchial epithelioma. The mean characteristics of the patient population were: age = 60 years (range: 48-70), weight=70kg (47-95), height=165cm (range 160-170) and serum creatinine=85microM (range 62-168). Plasma samples, two for each patient and lung samples, one for each patient, were obtained and analyzed. Seven groups were made according to the time of sampling after ingestion of the 5th dose. A three-compartment model was used to describe ciprofloxacin kinetics in plasma and lung. The non-linear mixed effect model approach was used to estimate the mean and variance of the pharmacokinetic parameters. The mean +/- SD of the estimates (coefficient of variation of interindividual variability as a percentage) were central volume of distribution, 39.45+/-52.47l(133%); steady-state volume of distribution, 145.86+/-97.51l(60%), clearance of influx into lung tissue, 35.83+/-22.57l/h(63%), extrapolated elimination rate constant, 0.173+/-0.25/h and extrapolated elimination half-life, 4.02+/-0.89h. The mean +/- SD ciprofloxacin concentration versus time curve in plasma and lung at steady state was simulated using pharmacokinetic parameters and lung physiological parameters, another approach was studied to model the transport of ciprofloxacin into the lung tissue by diffusion. Ciprofloxacin concentration-time history was obtained both by experiments or simulations. The ciprofloxacin level in the lung tissue followed the ciprofloxacin plasma level with a lag time resulting from the time necessary for ciprofloxacin to diffuse through the lung.
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A phenomenological turbulence model in which the energy spectrum obeys a nonlinear diffusion equation is analyzed. The general steady state contains a nonlinear mixture of the constant-flux Kolmogorov and fluxless thermodynamic components. Such "warm cascade" solutions describe a bottleneck phenomenon of spectrum stagnation near the dissipative scale. Transient self-similar solutions describing a finite-time formation of steady cascades are analyzed and found to exhibit nontrivial scaling behavior.
We compared quantitative experimental results on the diffusion of 35S-labeled phosphorothioate oligonucleotide (PS-ODN) after intraparenchymal infusion in rat brain, with the distributions predicted by Fick's second law of diffusion. Fischer 344 rats underwent identical intracerebral infusions of 36S-PS-ODN. After 0, 5, 11, 23, and 47 h, groups of animals were sacrificed and sequential brain cryosections subjected to autoradiography. The resulting experimental data were compared to the predicted distributions, for estimation of the apparent free diffusion coefficient, D*. Volumes of distribution and total content of 36 S-PS-ODN in the parenchyma were also computed, to monitor loss of total material. The values for D* were within the expected range for the 21-mer PS-ODN used, but a progressive decrease in D* over time was noted. The model requires D* to remain constant and, thus, does not adequately explain the spread of 35S-PS-ODN following infusion. The progressive slowing of spread over time suggests that at later time points, 35S-PS-ODN may be fixed by tissue binding or cellular uptake in the brain. Loss of material via vascular and CSF clearance may also contribute to the lack of fit. Our results highlight issues to be addressed in the modeling and experimental design of the intraparenchymal infusion process.
A model for consistent oxygen and glucose uptake by tumor cells is suggested. Oxygen uptake is considered to depend, under certain conditions, on that of glucose. Equations for calculation of oxygen and glucose distributions in cell spheroids are given (models of solid tumor in vitro).
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A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accumulation tendencies in the lower central area. Unlike countercurrent rotary drying, fluid bed drying cannot be accounted for by water diffusion inside the granule as the rate-limiting step. In its place, a model of external water vapor diffusion is proposed and is supported by vapor-concentration curves and by the linear dependence of the rate constants on the linear air velocities. The dried granulation exhibits the same trend as does countercurrent dried material in that larger particles have higher moisture contents than do smaller particles. Quantitative relationships between content of moisture and size were developed and are supported by experimental data. The granulation, upon storage, does not equilibrate, indicating that this type of water distribution is a problem in batch process granulations as well as in the earlier reported case of granulations for continuous production.
A physical model was derived for the synthesis of the antibiotic cephalexin with an industrial immobilized penicillin G acylase, called Assemblase. In reactions catalyzed by Assemblase, less product and more by-product are formed in comparison with a free-enzyme catalyzed reaction. The model incorporates reaction with a heterogeneous enzyme distribution, electrostatically coupled transport, and pH-dependent dissociation behavior of reactants and is used to obtain insight in the complex interplay between these individual processes leading to the suboptimal conversion. The model was successfully validated with synthesis experiments for conditions ranging from heavily diffusion limited to hardly diffusion limited, including substrate concentrations from 50 to 600 mM, temperatures between 273 and 303 K, and pH values between 6 and 9. During the conversion of the substrates into cephalexin, severe pH gradients inside the biocatalytic particle, which were previously measured by others, were predicted. Physical insight in such intraparticle process dynamics may give important clues for future biocatalyst design. The modular construction of the model may also facilitate its use for other bioconversions with other biocatalysts.
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One class of models of hair cell synaptic function that has been investigated in recent years consists of one or more reservoirs of synaptic material connected to other reservoirs and/or the synaptic cleft by means of diffusion paths. One such general model is considered here, comprising two reservoirs and a global source of synaptic material connected in series and releasing material into the synaptic cleft by a diffusion path characterized by an intensity-dependent permeability. The explicit form of the solution of the model for a sudden onset of stimulation is derived: The solution comprises two exponentially decaying terms plus a constant. This solution is shown to have a unique inverse. This allows the determination of the parameters of the model directly from experimental data from auditory-nerve fibers in the Mongolian gerbil. The behavior of the derived model parameters with variation of stimulus intensity is demonstrated, and implications for synaptic function are discussed.
A theoretical model describing the interaction between growth factor molecules and their receptors from the cell surface within an 'off-centre' diffusion approximation is developed in this paper. It is assumed that a number of non interacting particles (growth-factor molecules) more diffusively in the presence of traps (specific receptors) which are located at the surfaces of a number of cells uniformly distributed in space. The diffusion equations system is solved by a perturbative method. The model predicts a nonlinear dependence of the receptor occupation and of the time needed to reach a threshold value of receptor occupation on the total number of cell receptors. An autocrine binding, when the ligand is secreted by the responsive cells accounts for the interaction between IL-2 and helper T-cells.
To obtain optimal drying kinetics as well as quality of the dried product in a batch dryer, the energy required may be supplied by combining different modes of heat transfer. In this work, using potato slice as a model heat sensitive drying object, experimental studies were conducted using a batch heat pump dryer designed to permit simultaneous application of conduction and radiation heat. Four heat input schemes were compared: pure convection, radiation-coupled convection, conduction-coupled convection and radiation-conduction-coupled convection. A two-dimensional drying model was developed assuming the drying rate to be controlled by liquid water diffusion. Both drying rates and temperatures within the slab during drying under all these four heat input schemes showed good accord with measurements. Radiation-coupled convection is the recommended heat transfer scheme from the viewpoint of high drying rate and low energy consumption.
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