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PubMed1992

Mechanisms for intracellular distribution of mRNA: in situ hybridization studies in muscle.

The intracellular distribution of mRNA in striated muscle fibers is highly ordered, as is the structural organization of the fibers' contractile apparatus. Results from in situ hybridization of muscle mRNA are reviewed in an attempt to discern the mechanisms involved in mRNA distribution and to determine its relationship to developmental, growth, and repair processes in muscle. Nonradioactively labeled complementary RNA probes allow anatomic localization of mRNA at the light and electron microscopic level. Myosin mRNA in striated muscle is concentrated around transcriptionally active nuclei, myosin mRNA is excluded by the myofibrillar mass, myosin mRNA distribution correlates with that of cytoskeletal elements, and myosin mRNA is concentrated in regions of rapid growth and repair. The even distribution of myosin mRNA along the length of myofibrils gives no indication of specific association with either the thick or thin filaments. Of the possible mechanisms directing mRNA distribution, results from in situ hybridization and other analyses support a restricted diffusion model. Diffusion of mRNA (and polysomes) is severely limited by the myofibrillar lattice. It is possible that myosin mRNA is also associated with a cytoskeletal element, which may direct the mRNA to specific intracellular locations and affect translational activity.

Animals↗
PubMed1988

Effective axial diffusion in an expansile alveolar duct model.

Diffusion is described in an alveolar duct model, in which the following parameters are considered as variables: (1) ratio of lumen cross section to total cross section (s/S), (2) ratio of the diameter of the alveolar mouth opening to the mean alveolar width (AM/AW). A stochastic method is developed to determine a coefficient D*, which reflects the effective axial spread, for a wide range of (s/S) and (AM/AW). On the one hand, D* proves to be sensitive to (s/S); it is shown that the earlier suggestion to multiply the molecular diffusion coefficient by (s/S), slightly underestimated the effective axial spread. On the other hand, D* presents an extremely poor sensitivity to (AM/AW), in the range considered.

Diffusion↗
PubMed2002

Modeling the reversible, diffusive sink effect in response to transient contaminant sources.

A physically based diffusion model is used to evaluate the sink effect of diffusion-controlled indoor materials and to predict the transient contaminant concentration in indoor air in response to several time-varying contaminant sources. For simplicity, it is assumed the predominant indoor material is a homogeneous slab, initially free of contaminant, and the air within the room is well mixed. The model enables transient volatile organic compound (VOC) concentrations to be predicted based on the material/air partition coefficient (K) and the material-phase diffusion coefficient (D) of the sink. Model predictions are made for three scenarios, each mimicking a realistic situation in a building. Styrene, phenol, and naphthalene are used as representative VOCs. A styrene butadiene rubber (SBR) backed carpet, vinyl flooring (VF), and a polyurethane foam (PUF) carpet cushion are considered as typical indoor sinks. In scenarios involving a sinusoidal VOC input and a double exponential decaying input, the model predicts the sink has a modest impact for SBR/styrene, but the effect increases for VF/phenol and PUF/naphthalene. In contrast, for an episodic chemical spill, SBR is predicted to reduce the peak styrene concentration considerably. A parametric study reveals for systems involving a large equilibrium constant (K), the kinetic constant (D) will govern the shape of the resulting gasphase concentration profile. On the other hand, for systems with a relaxed mass transfer resistance, K will dominate the profile.

Air Movements↗
PubMedDate not supplied

[Numerical modeling of convection diffusion of endolymph in porous structures of the vestibular apparatus].

The mathematical algorithm of the diffusive model of vestibular reception is discussed. The conditions to reduce arising 3-dim boundary value problem to 1-dim one are found. And it is shown, that separate diffusive canaliculi as a mechanical transducers demonstrate the apparently clear properties of the frequency selectivity relating to their transduction of the endolymph space pressure into the endolymph concentration changes in their outputs. Some numerical experimental results are presented and discussed.

Diffusion↗
PubMed1990

Multilayer model of photon diffusion in skin.

A diffusion model describing the propagation of photon flux in the epidermal, dermal, and subcutaneous tissue layers of the skin is presented. Assuming that the skin is illuminated by a collimated, finite-aperture source, we develop expressions relating photon flux density within the skin and intensities re-emitted from the skin surface to the optical properties of the individual layers. Model simulations show that the rate at which re-emitted intensities diminish with radial distance away from the source can provide information about absorption and scattering in underlying tissues. Re-emitted intensities measured from homogeneous and two-layer tissue phantoms compare favorably with model predictions. We demonstrate potential applications of the model by estimating the absorption (sigma a) and transport-corrected scattering (sigma's) coefficients of dermis and subcutis from intensities measured from intact skin and by predicting the magnitude of the optical-density variations measured by a photoplethysmograph.

Diffusion↗
PubMed1985

A model for the diffusion of fluorescent probes in the septate giant axon of earthworm. Axoplasmic diffusion and junctional membrane permeability.

The diffusion of the three fluorescent probes dichlorofluorescein, carboxyfluorescein, and Lucifer Yellow within the septate median giant axon of the earthworm was monitored using fluorometric methods. A diffusion model was derived that allowed computation of the apparent axoplasmic diffusion coefficient, junctional membrane permeability (septal membranes), and plasma membrane permeability for each probe. Dichlorofluorescein and carboxyfluorescein have similar apparent axoplasmic diffusion coefficients, which were reduced by a factor of eight relative to that predicted from the Einstein-Stokes equation. Nonspecific reversible binding appears to be the major cause of the retarded diffusion coefficients. Junctional membrane permeability for dichlorofluorescein was 4.7 to 73-fold greater than that for carboxyfluorescein. This difference could not be explained on the basis of molecular size but can be explained by the difference in charge between the two molecules. Diffusion coefficients and junctional membrane permeabilities remained constant with time for both dyes. The diffusion of Lucifer Yellow within the axoplasm and permeability through the junctional membranes did not remain constant with time but declined. From this it was inferred that Lucifer Yellow experienced a slow, irreversible binding to axoplasmic elements. All three probes had finite plasma membrane permeabilities.

Animals↗
PubMedDate not supplied

A Brownian model of glutamate diffusion in excitatory synapses of hippocampus.

We simulated the diffusion of glutamate, following the release of a single vesicle from a pre-synaptic terminal, in the synaptic cleft by using a Brownian diffusion model based on Langevin equations. The synaptic concentration time course and the time course of quantal excitatory post-synaptic current have been analyzed. The results showed that they depend on the number of receptors located at post-synaptic membrane. Their time course are dependent both on the total number of the post-synaptic receptors and on the eccentricity of the pre-synaptic glutamate vesicle.

Glutamic Acid↗
PubMed2005

Modeling of diffusion with partitioning in stratum corneum using a finite element model.

Partitioning and diffusion of chemicals in skin is of interest to researchers in areas such as transdermal penetration and drug disposition, either for risk assessment or transdermal delivery. In this study a finite element method is used to model diffusion in the skin's outermost layer, the stratum corneum (SC). The SC is considered to be a finite two-dimensional composite having different diffusivity values in each medium as well as a partition coefficient at the interfaces between media. A commercial finite element package with thermal analysis capabilities is selected due to the flexibility of this software to handle irregular geometries. Partitioning is accommodated through a change of variables technique. This technique is validated by comparison of model results with analytical solutions of steady-state flux, transient concentration profiles, and time lag for diffusion in laminates. Two applications are presented. Diffusion is solved in a two-dimensional "brick and mortar" geometry that is a simplification of human stratum corneum, with a partition coefficient between corneocyte and lipid. Results are compared to the diffusion in multiple laminates to examine effects of the partition coefficient. The second application is the modeling of diffusion with partitioning through an irregular geometry which is obtained from a micrograph of hairless mouse stratum corneum.

Administration, Cutaneous↗
PubMed2003

A comparison of macaque behavior and superior colliculus neuronal activity to predictions from models of two-choice decisions.

Recently, models in psychology have been shown capable of accounting for the full range of behavioral data from simple two-choice decision tasks: mean reaction times for correct and error responses, accuracy, and the reaction time distributions for correct and error responses. At the same time, recent data from neural recordings have allowed investigation of the neural systems that implement such decisions. In the experiment presented here, neural recordings were obtained from superior colliculus prelude/buildup cells in two monkeys while they performed a two-choice task that has been used in humans for testing psychological models of the decision process. The best-developed psychological model, the diffusion model, and a competing model, the Poisson counter model, were explicitly fit to the behavioral data. The pattern of activity shown in the prelude/buildup cells, including the point at which response choices were discriminated, was matched by the evidence accumulation process predicted from the diffusion model using the parameters from the fits to the behavioral data but not by the Poisson counter model. These results suggest that prelude/buildup cells in the superior colliculus, or cells in circuits in which the superior colliculus cells participate, implement a diffusion decision process or a variant of the diffusion process.

Action Potentials↗
PubMed2005

Analysis of mass transport models for protein adsorption to cation exchanger by visualization with confocal laser scanning microscopy.

The mass transfer of bovine serum albumin (BSA) to a cation exchanger, SP Sepharose FF, has been studied by finite batch adsorption experiments. The uptake curve was simulated with three mass transport models (i.e., effective pore diffusion model, surface diffusion model and Maxwell-Stefan model) incorporating the particle size distribution of the adsorbent particles. All the three models can simulate the uptake curves reasonably well. However, how well these models could simulate the real concentration profile within the adsorbent particle cannot be verified by the fitness of the models to the uptake curve. Thus, confocal laser scanning microscopy (CLSM) was used to visualize protein uptake to the porous adsorbent particles during the batch experiments. Using a fluorescent dye-labeled bovine serum albumin (BSA) for the dynamic adsorption experiments, the radial concentration profiles of the labeled BSA molecules into individual adsorbent particles at different times were obtained from the CLSM images. The protein distribution profiles within various particle diameters at different time were compared with the radial protein distributions predicted from the models. It reveals that surface diffusion model describes the intraparticle protein concentration profiles better than the other two models.

Adsorption↗
PubMed1994

Protein folding dynamics: the diffusion-collision model and experimental data.

The diffusion-collision model of protein folding is assessed. A description is given of the qualitative aspects and quantitative results of the diffusion-collision model and their relation to available experimental data. We consider alternative mechanisms for folding and point out their relationship to the diffusion-collision model. We show that the diffusion-collision model is supported by a growing body of experimental and theoretical evidence, and we outline future directions for developing the model and its applications.

Diffusion↗
PubMed2005

Investigations of different kinetic models for zinc ions uptake by a natural zeolitic tuff.

The kinetics of uptake of zinc ions from aqueous solutions by natural zeolitic tuff has been investigated. Batch experiments at constant temperature and hydrodynamic conditions have been performed. A decrease in the initial zinc concentration in aqueous solutions prolongs the time needed for equilibrium. Various kinetic models including the film-diffusion model, the surface diffusion model and the heterogeneous diffusion model have been tested for the description of the experimental results of zinc concentration in the solution over time. Diffusion through the film and diffusion through the surface of the particle could be the rate limiting steps at the initial reaction time. However, the heterogeneous diffusion model seems to be the best model providing a satisfactory fitting of the experimental results from the beginning of the process to the point of equilibrium, particularly at lower initial zinc concentrations.

Kinetics↗
PubMedDate not supplied

Finite element modeling of diffusion and partitioning in biological systems: the infinite composite medium problem.

Four methods are proposed for modeling diffusion in heterogeneous media where diffusion and partition coefficients take on differing values in each subregion. The exercise was conducted to validate finite element modeling (FEM) procedures in anticipation of modeling drug diffusion with regional partitioning into ocular tissue, though the approach can be useful for other organs, or for modeling diffusion in laminate devices. Partitioning creates a discontinuous value in the dependent variable (concentration) at an intertissue boundary that is not easily handled by available general-purpose FEM codes, which allow for only one value at each node. The discontinuity is handled using a transformation on the dependent variable based upon the region-specific partition coefficient. Methods were evaluated by their ability to reproduce a known exact result, for the problem of the infinite composite medium (Crank, J. The Mathematics of Diffusion, 2nd ed. New York: Oxford University Press, 1975, pp. 38-39.). The most physically intuitive method is based upon the concept of chemical potential, which is continuous across an interphase boundary (method III). This method makes the equation of the dependent variable highly nonlinear. This can be linearized easily by a change of variables (method IV). Results are also given for a one-dimensional problem simulating bolus injection into the vitreous, predicting time disposition of drug in vitreous and retina.

Biological Transport, Active↗
PubMed1989

Analysis of drug penetration through the skin by the two-layer skin model.

A diffusion model for the skin penetration of drug in the finite-dose system was developed considering the skin to be composed of two layers, the outermost layer (stratum corneum) and the lower layer (viable epidermis and dermis). Based on this skin model, the Laplace transforms of the equations for the drug amounts in the receptor, the vehicle, and the skin were derived. The penetration profiles of 6-mercaptopurine (6-MP) through the intact and stripped guinea pig skin were obtained from in vitro diffusion experiments. The computer fitting of those profiles to the Laplace-transformed equations by a nonlinear least-squares program based on a fast inverse Laplace transform algorithm [MULTI-(FILT)] gave parameters such as diffusion coefficients of 6-MP and thicknesses of both layers. The mean transit time (MTT) for each diffusion process was defined based on statistical moment concept and calculated using the obtained parameters. Under the present condition, the process to move from the vehicle to the stratum corneum is demonstrated to have the longest mean time in overall processes of 6-MP penetration.

Animals↗
PubMed2001

Unfolding rates for the diffusion-collision model.

In the diffusion-collision model, the unfolding rates are given by the likelihood of secondary structural cluster dissociation. In this work, we introduce an unfolding rate calculation for proteins whose secondary structural elements are alpha helices, modeled from thermal escape over a barrier that arises from the free energy in buried hydrophobic residues. Our results are in good agreement with currently accepted values for the attempt rate.

Biophysical Phenomena↗
PubMed2000

A comparison of two response time models applied to perceptual matching.

Two models, a Poisson race model and a diffusion model, are fit to data from a perceptual matching task. In each model, information about the similarity or the difference between two stimuli accumulates toward thresholds for either response. Stimulus variables are assumed to influence the rate at which information accumulates, and response variables are assumed to influence the level of the response thresholds. Three experiments were conducted to assess the performance of each model. In Experiment 1, observers performed under different response deadlines; in Experiment 2, response bias was manipulated by changing the relative frequency of same and different stimuli. In Experiment 3, stimulus pairs were presented at three eccentricities: foveal, parafoveal, and peripheral. We examined whether the race and diffusion models could fit the response time and accuracy data through changes only in response parameters (for Experiments 1 and 2) or stimulus parameters (for Experiment 3). Comparisons between the two models suggest that the race model, which has not been studied extensively, can account for perceptual matching data at least as well as the diffusion model. Furthermore, without the constraints on the parameters provided by the experimental conditions, the diffusion and the race models are indistinguishable. This finding emphasizes the importance of fitting models across several conditions and imposing logical psychological constraints on the parameters of models.

Adult↗
PubMed1994

Comparison of two otitis media models for the study of middle ear antimicrobial pharmacokinetics.

We compared two models of acute otitis media that estimate middle ear antimicrobial pharmacokinetics. Using a crossover study design, we compared a systemic drug administration model with a diffusion model we devised that measures the disappearance of antimicrobials from the middle ear. We induced acute otitis media in 14 chinchillas by inoculating S. pneumoniae into the middle ear, then administered 3 antimicrobials: amoxicillin, trimethoprim, and sulfamethoxazole. Next we collected middle ear fluid samples to analyze drug concentrations and compare rate constants for the systemic and diffusion models by analysis of variance. We found that amoxicillin K values were not affected by model testing sequence (p = 0.827) or model type (systemic versus diffusion, p = 0.310), nor were sulfamethoxazole K values: model testing sequence (p = 0.917), model type (p = 0.963). Trimethoprim K values were also not affected by model testing sequence (p = 0/760), but were by model type (p = 0.0001). Trimethoprim elimination from the diffusion model was faster (K = 0.33 +/- 0.17 versus 0.57 +/- 0.09 hr-1) than from the systemic model, although it appears this was caused by sampling before drug distribution into the middle ear was complete. In conclusion, it appears K values derived from either systemic antimicrobial administration or direct middle ear instillation are similar for assessing middle ear antimicrobial pharmacokinetics, and these models can be used interchangeably to study factors affecting otitis media treatment response.

Amoxicillin↗