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PubMed1995

A diffusion-reaction model of nerve regeneration.

The process of peripheral nerve regeneration has been modeled using 5 populations of mathematical variables to represent the biological activities of Wallerian degeneration, fibrin matrix development, Schwann cell activity, elongating neurites, and neovascularization. The mathematical model provided simulations of nerve regeneration following transection and crush injuries that correspond with growth behaviors quantified in biological experiments. Neovascularization was spatiotemporally quantified in nerve regeneration chambers and following nerve crush injury in order to test the simulations of the mathematical model. The vasculature in both the chamber and following nerve crush responded as predicted by the model, increasing beyond normal levels to a peak only to decrease back to normal. This behavior appeared as a traveling wave in the proximal-distal direction preceeding the major thrust of neuritic outgrowth suggesting that development of the vasculature is a rate-limiting step in nerve regeneration.

Animals↗
PubMed2003

Aging dynamics in globular proteins: summary and analysis of experimental results and simulation by a modified trap model.

Recent results of spectral diffusion experiments by spectral hole-burning techniques carried out at cryogenic temperatures on various monomeric heme proteins unequivocally show interesting new features of conformational dynamics of globular proteins that were not emphasized in the literature until now. These new aspects of the protein dynamics are anomalous diffusion and the aging effect. Here, using the similarities between proteins and glassy systems, we present a model which can interpret the line broadening and-through this effect-the aging phenomenon as well. Leaving untouched the widely accepted energy landscape (EL) concept for the general description of protein dynamics, we concentrate on the bottom of the funnel-like EL, because this part corresponds to the native state(s) at low temperature. We suggest that the overall shape of the EL at the lowest energy range is rather smooth, but on a finer scale it consists of traps. The dynamics is defined by sequential jumps among these traps and the process is described by a Master equation, where the hopping rate only depends on the parameters of the starting state. This model was adapted to interpret the common results of spectral diffusion experiments. We tested our model in the simplest case by computer simulation, and it shows excellent agreement with the experimental data. To our knowledge this is the first work where a theoretical interpretation of the aging dynamics of proteins is directly and quantitatively related to the experimental observations. We also show that the model, after the generalization that the traps are hierarchically organized, is in accordance with the concept of other well-known EL models.

Biophysical Phenomena↗
PubMed1996

Gamma sterilization of UHMWPE articular implants: an analysis of the oxidation problem. Ultra High Molecular Weight Poly Ethylene.

Gamma irradiation of Ultrahigh Molecular Weight Polyethylene (UHMWPE) leads to long-lived free radicals which react with oxygen. Diffusion of oxygen, occurring over months or years, controlled by the permeability characteristics of the polymer, results in progressive oxidation, breaking of polymer chains, alteration of the crystalline portion of the polymer, and deterioration of the mechanical properties of the polymer. This paper reviews the observations in the literature on this issue and then presents a conceptual model concerning the interplay of radical diffusion, oxygen diffusion, non-uniform permeability, and free-radically driven chain reactions in order to explain these observations. The suggested model is based on literature that is available on the oxidation of linear polyethylenes during and after irradiation. The model directs the attention of researchers in the field of orthopaedic implants to the complexity of the process and the variety of issues and parameters to be considered while studying the long-term effects of radiation sterilization on UHMWPE.

Biopolymers↗
PubMed2003

An enhanced cosmic-ray flux towards zeta Persei inferred from a laboratory study of the H3+-e- recombination rate.

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many molecules. In dense interstellar clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density and temperature. But observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. Models of diffuse clouds have, however, been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons (e-), the electron fraction, and the cosmic-ray ionization rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards Persei) where the electron fraction is already known. From these, we find that the cosmic-ray ionization rate along this line of sight is 40 times faster than previously assumed. If such a high cosmic-ray flux is ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.

Journal Article↗
PubMed2005

Mapping hazard from urban non-point pollution: a screening model to support sustainable urban drainage planning.

Non-point sources of pollution are difficult to identify and control, and are one of the main reasons that urban rivers fail to reach the water quality objectives set for them. Whilst sustainable drainage systems (SuDS) are available to help combat this diffuse pollution, they are mostly installed in areas of new urban development. However, SuDS must also be installed in existing built areas if diffuse loadings are to be reduced. Advice on where best to locate SuDS within existing built areas is limited, hence a semi-distributed stochastic GIS-model was developed to map small-area basin-wide loadings of 18 key stormwater pollutants. Load maps are combined with information on surface water quality objectives to permit mapping of diffuse pollution hazard to beneficial uses of receiving waters. The model thus aids SuDS planning and strategic management of urban diffuse pollution. The identification of diffuse emission 'hot spots' within a water quality objectives framework is consistent with the 'combined' (risk assessment) approach to pollution control advocated by the EU Water Framework Directive.

Cities↗
PubMed1988

An in-vivo model to examine the electromyographic activity of isolated myometrial tissue from pregnant sheep.

Strips (2.5 x 3.5 cm) of myometrium alone (MYO) or endometrium/myometrium (ENDO/MYO) were removed from the pregnant horn of sheep (Day 110 of gestation) and transplanted to sites within the omental fat. These explants developed regular bursts of electromyographic (EMG) activity over a period of 7-10 days, as well as a dose-dependent stimulatory response to oxytocin (50-200 mU i.v.). The frequency (per 2 h) of EMG bursts in the MYO (5.3 +/- 0.2) and ENDO/MYO (5.2 +/- 0.3) explants was significantly greater (P less than 0.05) than that of the uterine myometrium (3.0 +/- 0.1), while burst duration (min) in MYO (4.1 +/- 0.2) and ENDO/MYO (4.1 +/- 0.2) explants was significantly (P less than 0.05) less than in the uterine myometrium (7.3 +/- 0.1). The EMG bursts were asynchronous between the explants and uterus, although systemic administration of oxytocin produced a synchronous burst of EMG activity in all three tissues. No differences in EMG activity or responsiveness were apparent between MYO and ENDO/MYO explants. Histological examination of the explant tissue revealed the presence of smooth muscle fibres regularly orientated into two layers; some loss of endometrial tissue was apparent in ENDO/MYO explants. To validate the mechanical integrity of this model we examined the in-vitro contractile activity of myometrial strips prepared from the explants. The strips developed regular spontaneous contractions and demonstrated a dose-dependent stimulation in response to the addition of oxytocin (10(-10) to 10(-4) M) to the bath fluid. These results suggest that spontaneous contractures during pregnancy are probably not due to pulsatile release of stimulants into the systemic circulation, or the direct diffusion of stimulants from intrauterine tissues to the myometrium but are probably caused by factors within the myometrium itself.

Animals↗
PubMed2002

A novel method for preparation of animal models of liver damage: liver targeting of carbon tetrachloride in rats.

Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.

Animals↗
PubMed2000

Estimating mean monthly incident solar radiation on horizontal and inclined slopes from mean monthly temperatures extremes.

Although satellite-borne sensors are now available to estimate cloud cover and incoming short-wave radiation across the Earth's surface, the study of climatic variation and its impact on terrestrial and marine ecosystems involves historical analyses of data from networks of weather stations that only record extremes in temperatures and precipitation on a daily basis. Similarly, when projections are made with global atmospheric circulation models, the spatial resolution of predicted radiation is too coarse to incorporate the effects of heterogeneous topography. In this paper, we review the development and set forth a set of general equations that allow both diffuse and direct solar radiation to be estimated for each month on the basis of mean daily maximum and minimum temperatures, latitude, elevation, slope, and aspect. Adjustments for differences in slope, aspect, and elevation are made by varying the fraction of diffuse and direct solar beam radiation. To test the equations on various slopes and under different climatic conditions, we drew on highquality radiation data recorded at a number of sites on three continents. On horizontal surfaces the set of equations predicted both direct and diffuse components of solar radiation within 1%-7% of recorded values. On slopes, estimates of monthly mean solar radiation were with 13% of observed values with a mean error of less than 2 MJ m(-2) day(-1) over any given month.

Background Radiation↗
PubMed2004

Modeling antibiotic tolerance in biofilms by accounting for nutrient limitation.

A mathematical model of biofilm dynamics was used to investigate the protection from antibiotic killing that can be afforded to microorganisms in biofilms based on a mechanism of localized nutrient limitation and slow growth. The model assumed that the rate of killing by the antibiotic was directly proportional to the local growth rate. Growth rates in the biofilm were calculated by using the local concentration of a single growth-limiting substrate with Monod kinetics. The concentration profile of this metabolic substrate was calculated by solving a reaction-diffusion problem. The model predicted the following features: stratified patterns of growth with zones of no growth in the biofilm interior, slow killing of biofilm microorganisms that was further retarded as the initial biofilm thickness increased, nonuniform spatial patterns of killing inside the biofilm, biofilm killing rates that decrease in a nonlinear way as the concentration of the growth-limiting substrate feeding the biofilm is decreased, and heightened tolerance when external mass transfer resistance is manifested. This modeling study also provides motivation for further investigation of a hypothetical cell state in which damaged cells score as nonviable but continue to consume substrate. The existence of such a cell state can further retard biofilm killing, according to the simulations. The results support the important contributions of nutrient limitation and slow growth to the antibiotic tolerance of microorganisms in biofilms.

Anti-Bacterial Agents↗
PubMed1978

Estimation of dissolution rate of salicylamide in complexing media using a theoretical diffusion model.

Dissolution rates of salicylamide in water and caffeine solutions under perfect sink conditions were predicted by theoretical diffusion equations applicable to dissolution in complexing media. Experimental dissolution rates were measured using a compartmentalized rotating-basket apparatus under two sets of conditions. Agreement was found between experimental and predicted rates. Use of the theoretical equation for estimating dissolution rates involves simple calculations of diffusion coefficients and diffusion layer thickness under the operative dissolution conditions. The increase in dissolution rate caused by addition of the complexant can be calculated for diffusion-controlled dissolution directly if the stability constant and the drug solubility in water are known or measured.

Caffeine↗
PubMed2004

Role of diffusion in branching and annihilation random walk models.

Different branching and annihilating random walk models are investigated by the cluster mean-field method and simulations in one and two dimensions. In the case of the A-->2A , 2A--> 0 model the cluster mean-field approximations show diffusion dependence in the phase diagram as was found recently by the nonperturbative renormalization group method [Phys. Rev. Lett. 92, 255703 (2004)]]. The same type of survey for the A-->2A , 4A--> 0 model results in a reentrant phase diagram, similar to that of the 2A-->3A , 4A--> 0 model [Phys. Rev. E 69, 036112 (2004)]]. Simulations of the A-->2A , 4A--> 0 model in one and two dimensions confirm the presence of both the directed percolation transitions at finite branching rates and the mean-field transition at zero branching rate. In two dimensions the directed percolation transition disappears for strong diffusion rates. These results disagree with the predictions of the perturbative renormalization group method.

Journal Article↗
PubMed2000

The paradox of physicians and administrators in health care organizations.

Rapidly changing times in health care challenge both physicians and health care administrators to manage the paradox of providing orderly, high quality, and efficient care while bringing forth innovations to address present unmet problems and surprises that emerge. Health care has grown throughout the past several centuries through differentiation and integration, becoming a highly complex biological system with the hospital as the central attractive force--or "strange attractor"--during this century. The theoretical model of complex adaptive systems promises more effective strategic direction in addressing these chaotic times where the new strange attractor moves beyond the hospital.

Clinical Medicine↗
PubMed2005

Mouse models of subcutaneous spleen reservoir for multiple portal venous injections to treat liver malignancies.

Dog and rat animal models have been developed for repeated intravascular administrations to the liver. However, mice have generally been considered too small to use for these models. This study describes the development of mouse models that permit the establishment of liver metastases that can be subsequently treated by repeated injections into the portal venous system. A mini-laparotomy is done to mobilize the spleen and transpose it to a s.c. pocket with its vascular pedicle intact. A suspension of single tumor cells is then inoculated into the portal vein to establish diffuse liver metastases. These tumors may be treated by simple percutaneous injections directly into the s.c. whole spleen reservoir. The ease of injection into the s.c. spleen permits repeated injections into the portal venous system. The usefulness of this model was shown in experiments revealing that multiple portal venous administrations of a replication-conditional, oncolytic herpes simplex virus mutant are more effective than a single portal venous administration. In a modification of this model, the spleen is first split into two, leaving intact the vascular pedicle for each half of the spleen. Tumor cells are inoculated into one hemi-spleen, which is then resected 10 minutes later. The other hemi-spleen is transposed to the s.c. position, thereby permitting subsequent repetitive portal venous injections via percutaneous injections into the s.c. hemi-spleen. These mouse models are useful for a wide range of studies.

Animals↗
PubMed2001

Anisotropy in high angular resolution diffusion-weighted MRI.

The diffusion in voxels with multidirectional fibers can be quite complicated and not necessarily well characterized by the standard diffusion tensor model. High angular resolution diffusion-weighted acquisitions have recently been proposed as a method to investigate such voxels, but the reconstruction methods proposed require sophisticated estimation schemes. We present here a simple algorithm for the identification of diffusion anisotropy based upon the variance of the estimated apparent diffusion coefficient (ADC) as a function of measurement direction. The rationale for this method is discussed, and results in normal human subjects acquired with a novel diffusion-weighted stimulated-echo spiral acquisition are presented which distinguish areas of anisotropy that are not apparent in the relative anisotropy maps derived from the standard diffusion tensor model. Published 2001 Wiley-Liss, Inc.

Algorithms↗
PubMed2001

Thermal and physical properties of bakery products.

This article reviews the measurement techniques, prediction models, and data on thermo-physical properties of bakery products: specific heat, thermal conductivity, thermal diffusivity, and density. Over the last decade, investigation has focused more on thermo-physical properties of nonbread bakery products. Both commonly used and new measurement techniques for thermo-physical properties reported in the publication are presented with directions for their proper use. Data and prediction models are tabulated for the range of moisture content and temperature of the bakery products.

Bread↗
PubMed2004

Underlying mechanism of numerical instability in large-eddy simulation of turbulent flows.

This paper extends our recent theoretical work concerning the feasibility of stable and accurate computation of turbulence using a large eddy simulation [Phys. Rev. E 68, 036705 (2003)]]. In our previous paper, it was shown, based on a simple assumption regarding the instantaneous streamwise velocity, that the application of the Gaussian filter to the incompressible Navier-Stokes equations can result in the appearance of a numerically unstable term that can be decomposed into positive and negative viscosities. That result raises the question as to whether an accurate solution can be achieved by a numerically stable subgrid-scale model. In the present paper, based on assumptions regarding the statistically averaged velocity, we present similar theoretical investigations to show that in several situations, the shears appearing in the statistically averaged velocity field numerically destabilize the fluctuation components because of the derivation of a numerically unstable term that represents negative diffusion in a fixed direction. This finding can explain the problematic numerical instability that has been encountered in large eddy simulations of wall-bounded flows. The present result suggests that this numerical problem is universal in large eddy simulations, and that if there is no failure in modeling, the resulting subgrid-scale model can still have unstable characteristics; that is, the known instability problems of several existing subgrid-scale models are not something that one may remove simply by an artificial technique, but must be taken seriously so as to treat them accurately.

Journal Article↗
PubMed1980

Effect of self-association of phenol on its transport across polyethylene film.

Phenol diffusion across a high density polyethylene film from isooctane, in which phenol self-associates, demonstrated nonideal behavior. The steady-state flux of phenol across the film was not directly proportional to its concentration in the donor phase. At higher donor phase concentrations, negative steady-state flux deviations were observed. These negative deviations were due to phenol self-association in the donor phase and the resulting decreases in thermodynamic activity. By using a monomer--pentamer model for phenol self-association in isooctane, the steady-state flux was shown to be directly proportional to the phenol monomer concentration in the donor phase. Although steady-state flux concentration deviations were observed, the diffusion time lag was independent of the permeant concentration and reflected the intrinsic diffusivity of the film to phenol.

Chemical Phenomena↗
PubMed2005

Selective visualisation of neuroepithelial bodies in vibratome slices of living lung by 4-Di-2-ASP in various animal species.

Pulmonary neuroepithelial bodies (NEBs) are extensively innervated organoid groups of neuroendocrine cells that lie in the epithelium of intrapulmonary airways. Our present understanding of the morphology of NEBs is comprehensive, but direct physiological studies have so far been challenging because the extremely diffuse distribution of NEBs makes them inaccessible in vivo and because a reliable in vitro model is lacking. Our aim has been to optimise an in vitro method based on vibratome slices of living lungs, a model that includes NEBs, the surrounding tissues and at least part of their complex innervation. This in vitro model offers satisfactory access to pulmonary NEBs, provided that they can be differentiated from other tissue elements. The model was first optimised for living rat lung slices. Neutral red staining, reported to stain rabbit NEBs, proved unsuccessful in rat slices. On the other hand, the styryl pyridinium dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (4-Di-2-ASP), showed brightly fluorescent cell groups, reminiscent of NEBs, in the airway epithelium of living lung slices from rat. In addition, nerve fibres innervating the NEBs were labelled. The reliable and specific labelling of pulmonary NEBs by 4-Di-2-ASP was corroborated by immunostaining for protein gene-product 9.5. Live cell imaging and propidium iodide staining further established the acceptable viability of 4-Di-2-ASP-labelled NEB cells in lung slices, even over long periods. Importantly, the in vitro model and 4-Di-2-ASP staining procedure for pulmonary NEBs appeared to be equally reproducible in mouse, hamster and rabbit lungs. Diverse immunocytochemical procedures could be applied to the lung slices providing an opportunity to combine physiological and functional morphological studies. Such an integrated approach offers additional possibilities for elucidating the function(s) of pulmonary NEBs in health and disease.

Animals↗