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PubMed2006

Continuous photobleaching in vesicles and living cells: a measure of diffusion and compartmentation.

We present a comprehensive and analytical treatment of continuous photobleaching in a compartment, under single photon excitation. In the very short time regime (t<0.1 ms), the diffusion does not play any role. After a transition (or short time regime), one enters in the long time regime (t>0.1-5 s), for which the diffusion and the photobleaching balance each other. In this long time regime, the diffusion is either fast (i.e., the photobleaching probability of a molecule diffusing through the laser beam is low) so that the photobleaching rate is independent of the diffusion constant and dependent only of the laser power, or the diffusion is slow (i.e., the photobleaching probability is high) and the photobleaching rate is mainly dependent on the diffusion constant. We illustrate our theory by using giant unilamellar vesicles ranging from approximately 10 to 100 microm in diameter, loaded with molecules of various diffusion constants (from 20 to 300 microm2/s) and various photobleaching cross sections, illuminated under laser powers between 3 and 100 microW. We also demonstrated that information about compartmentation can be obtained by this method in living cells expressing enhanced green fluorescent proteins or that were loaded with small FITC-dextrans. Our quantitative approach shows that molecules freely diffusing in a cellular compartment do experience a continuous photobleaching. We provide a generic theoretical framework that should be taken into account when studying, under confocal microscopy, molecular interactions, permeability, etc.

Biophysics↗
PubMed1991

Where have all the doctors gone? (2). Intraurban trends: changes in the geographic distribution of general practitioners in Auckland, 1980-7.

During the 1980s the Auckland metropolitan area increased its share of all general practitioners in New Zealand at a much faster rate than its share of the population, resulting in a high level of availability by 1987. In the light of such trends, neoclassical theory would predict a diffusion of general practitioners into areas with fewer doctors where there is less competition for patients. Data for 1980-7, however, indicates that for every FTE general practitioner who located in doctor poor areas of the city, 1.87 general practitioners continued to open practices in areas already well provided for. Or, for every extra consultation that took place in low income suburbs, 1.51 extra consultations occurred in more affluent localities. These results do not provide strong support for a market led diffusion of doctors into areas of need and any gains in increased equity appear to have been achieved at the expense of considerable inefficiency given the likely presence of induced demand.

Catchment Area, Health↗
PubMed1979

Immunoglobulins of normal aqueous humour.

Immunoglobulin levels have been measured in aqueous humour and blood from 79 patients undergoing cataract extraction. A linear relationship between serum and aqueous IgG was found, but this was not so for IgA, and IgM was not detected in any of the aqueous samples. The morphological features of both the blood-ocular and the blood-brain-cerebrospinal fluid barriers, and the influences governing the passage of immunoglobulins across these barriers are considered. The similarity between two theories of protein penetration, diffusion through the iris root into the eye, and via the "functional leak" into the cerebrospinal fluid, are considered. We feel that the discrepancy between IgG and IgA penetrations into aqueous, despite their similar molecular weights, may be due in part to the larger hydrodynamic volume and consequently increased frictional ration of IgA, although the existence of selective IgG transfer has not been excluded.

Aqueous Humor↗
PubMed1986

[Present diagnostic status of scirrhous type gastric cancer--with special reference to the endoscopic diagnosis].

First, we presented an actual diagnostic situation in nowadays for gastric cancer of Borrmann 4, which is virtually the same as scirrhous gastric cancer. Among 12 patients treated by the author, all of whom were discovered late, only 3 underwent surgery. In fact, with inoperable cases in Borrmann 4, even those endoscopically found to show insufficient stretching of the gastric wall, thickening and tortuosity of folds, uneven gastric mucosa, redness and white coating, there may be negative in gastric biopsy. However, the significance of an endoscopic examination for diagnosis of scirrhous cancer is in obtaining proof of the carcinoma (especially when still operable) by gastric biopsy. Thus, one must strive not to overlook slight redness, white coating which means small erosions, but to go over gastric biopsy again and again. Next, with carcinoma presenting a leather bottle (linitis plastica type) of the stomach itself, the II c portion of the stomach consisted of fundic glands (undifferentiated carcinoma) shall become the primary focus supporting Nakamura's theory. One case of diffuse invasive cancer, mistakenly diagnosed as a II c case, and two cases of regional type, one similar to II c and the other a Borrmann 2 carcinoma of advanced carcinoma showing strongly fibrous scirrhous tendency toward infiltration, were jointly monitored.

Adenocarcinoma, Scirrhous↗
PubMed1997

[Intestinal permeability].

Intestinal mucosa has an absorptive function and acts also as a selective barrier against potential antigenic, toxic and carcinogenic substances. Intestinal permeability can be defined as the capacity of mucosal surface to be penetrate by specific substances through unmediated diffusion. There are two theories about molecular permeation routes: the first one hypothesizes a transcellular (through small pores), a paracellular (through big channels) and a lipophilic pathways; the second one gives a key role only to paracellular tight-junctions. In many diseases we can find changes in intestinal permeability evaluable by simple and non invasive tests, administering "per os" probe molecules. These substances cross the epithelium in different way and amount according to their physicochemical features and mucosal integrity; then they reach circulation and are eliminated in urines where they can be detected. The most frequently molecules used are mono/disaccharides, 51Cr-labelled ethylenediaminetetraacetate (51Cr-EDTA) and polyethylene glycol (PEG). This simple method has become more and more used for diagnostic and speculative aims. These intestinal permeability tests have a low specificity so they cannot be used for a definitive diagnosis of intestinal disease; nevertheless, the high sensitivity for intestinal mucosal damage could make them a necessary method to evaluate mucosal integrity after therapy, to select patients with a specific symptoms and to support, particularly in pediatric populations, more specific and invasive diagnostic tests.

Humans↗
PubMed1979

Diffusion-controlled reactions on spherical surfaces. Application to bacteriophage tail fiber attachment.

We have explored the kinetic implications of a model that may account for the acceleration of tail fiber (F) attachment to baseplates (B) by whiskers (W) on bacteriophage T4. The model assumes that a W-F complex is formed initially, and that the tethered fiber then undergoes rotational diffusion until a B-F encounter takes place. In the absence of whiskers, B-F complexes must form unassisted. Formation of a W-F intermediate will accelerate F attachment to B if (a) the bimolecular rate constant for W-F complex formation is larger than that for direct B-F interaction and (b) subsequent rotational diffusion of the tip of F to B is not much slower than the dissociation of W-F. Condition a was investigated by applying a recent theory of orientational effects on translational diffusion-controlled reactions. This theory suggests that substantial rate enhancement is expected if the reaction half-angle theta 0 is larger for W-F than for B-F complex formation. Condition b was investigated by calculating the mean and the variance of the time required for the diffusion of a molecule (the proximal tip of the fiber) on a spherical surface (whose radius is the distance from the tip to the whisker tethering point) into a circular sink (the baseplate site). The mean time is on the order of the inverse rotational diffusion coefficient, DR, of the fiber, but is sensitive to theta 0. Both conditions are satisfied for plausible choices of parameters. The solution to the diffusion equation we have obtained should have application to other physical situations, such as the rate of quenching of a fluorophore as it diffuses on the surface of a spherical membrane into proximity with a quencher.

Diffusion↗
PubMed2006

Scaling behavior of nonhyperbolic coupled map lattices.

Coupled map lattices of nonhyperbolic local maps arise naturally in many physical situations described by discretized reaction diffusion equations or discretized scalar field theories. As a prototype for these types of lattice dynamical systems we study diffusively coupled Tchebyscheff maps of Nth order which exhibit strongest possible chaotic behavior for small coupling constants a. We prove that the expectations of arbitrary observables scale with sqrt of a in the low-coupling limit, contrasting the hyperbolic case which is known to scale with a . Moreover we prove that there are log-periodic oscillations of period ln N2 modulating the sqrt of a dependence of a given expectation value. We develop a general 1st order perturbation theory to analytically calculate the invariant one-point density, show that the density exhibits log-periodic oscillations in phase space, and obtain excellent agreement with numerical results.

Journal Article↗
PubMed1990

Echo-planar imaging of intravoxel incoherent motion.

The recently established single-shot technique of echo-planar imaging of intravoxel incoherent motion (IVIM) for determining and imaging the variations of microscopic motions of water has been applied to studies of water perfusion in phantoms and to in vivo studies of diffusion and perfusion in cat and human brains. The phantom results demonstrate that perfusion levels comparable with those found in vivo have easily observable and reproducible effects on signal amplitude that are consistent with previous IVIM theory. Reliable measurements of the diffusion coefficient in various types of brain tissue have been obtained. The results for white matter are consistent with the existence of anisotropic diffusion in oriented bundles of myelinated nerve fibers. The results for gray matter can be fitted to the IVIM theory and suggest a value of up to 14% for the fraction of the signal contributed by randomly perfusing fluid in normal cerebral cortex.

Animals↗
PubMed1999

Irreversible adsorption of diffusing hard disks: an effective medium approach.

We propose an effective medium theory to analyze the kinetics of nonsequential adsorption of colloidal particles, including transport and blocking effects, valid at all values of surface coverage. The theory is applied to the irreversible adsorption of diffusing hard disks obtaining a kinetic law, which is in excellent agreement with nonsequential computer simulations at all densities of adsorbed particles.

Journal Article↗
PubMed1980

Proton transport across charged membrane and pH oscillations.

Based on Eyring's multibarrier activation process, a mathematical model and equation is developed to account for proton diffusion through an immobilized protein and enzyme membrane perfused with an electrolyte, substrate, and a buffer. With this model we find that, in the presence of a buffer, our solution approaches the continuum case very rapidly. We apply our model to membranes composed of papain and bovine serum albumin and find that our theory closely stimulates the experimental observations on the effect of salt and buffer on proton diffusion. Our theory shows that the pH oscillations observed in the diffusion controlled papain-benzoyl-L-arginine ethyl ester (BAEE) reaction may be the result of CO2 dissolved in the bath at high pH. In our theory, under certain conditions and in agreement with experimental observation, the buffer penetration depth oscillates near the boundary of a papain membrane in a solution containing BAEE and borate. We also find that at low ionic strength small ions as well as a buffer are seen to oscillate if a membrane is highly charged.

Biological Transport, Active↗
PubMed1985

Effects of diffusion on the electrophoretic behavior of associating systems: the Gilbert-Jenkins theory revisited.

The Gilbert-Jenkins theory predicts the asymptotic shape of moving-boundary sedimentation and electrophoretic patterns and broad zone molecular sieve chromatographic elution profiles for the class of interacting systems, A + B in equilibrium C, in which two dissimilar macromolecules react reversibly to form a complex. A particularly provocative case is the one in which the complex has a greater migration velocity than that of either reactant, each of which has a different velocity. Depending upon conditions, this case predicts, for example, that in the asymptotic limit an ascending electrophoretic pattern or a frontal gel chromatographic elution profile can show two hypersharp reaction boundaries separated by a plateau. This prediction is now confirmed by numerical solution of transport equations which retain the second-order diffusional term and extrapolation of the computed patterns to zero diffusion coefficient. For finite diffusion coefficient, however, the two hypersharp reaction boundaries are separated by a weak negative gradient. These calculations are extended to an examination of the transitions between the three types of patterns admitted by the case under consideration in order to gain physical understanding and to define criteria for recognizing the transitions. Studies of this kind not only establish confidence in the Gilbert-Jenkins theory, but, in addition, they provide new insights which make for more effective application of the theory to real systems.

Diffusion↗
PubMed2005

Statistical-mechanical theory of rheology: Lennard-Jones fluids.

The generalized Boltzmann equation for simple dense fluids gives rise to the stress tensor evolution equation as a constitutive equation of generalized hydrodynamics for fluids far removed from equilibrium. It is possible to derive a formula for the non-Newtonian shear viscosity of the simple fluid from the stress tensor evolution equation in a suitable flow configuration. The non-Newtonian viscosity formula derived is applied to calculate the non-Newtonian viscosity as a function of the shear rate by means of statistical mechanics in the case of the Lennard-Jones fluid. For that purpose we have used the density-fluctuation theory for the Newtonian viscosity, the modified free volume theory for the self-diffusion coefficient, and the generic van der Waals equation of state to compute the mean free volume appearing in the modified free volume theory. Monte Carlo simulations are used to calculate the pair-correlation function appearing in the generic van der Waals equation of state and shear viscosity formula. To validate the Newtonian viscosity formula obtained we first have examined the density and temperature dependences of the shear viscosity in both subcritical and supercritical regions and compared them with molecular-dynamic simulation results. With the Newtonian shear viscosity and thermodynamic quantities so computed we then have calculated the shear rate dependence of the non-Newtonian shear viscosity and compared it with molecular-dynamics simulation results. The non-Newtonian viscosity formula is a universal function of the product of reduced shear rate (gamma*) times reduced relaxation time (taue*) that is independent of the material parameters, suggesting a possibility of the existence of rheological corresponding states of reduced density, temperature, and shear rate. When the simulation data are reduced appropriately and plotted against taue*gamma* they are found clustered around the reduced (universal) non-Newtonian viscosity formula. Thus we now have a molecular theory of non-Newtonian shear viscosity for the Lennard-Jones fluid, which can be implemented with a Monte Carlo simulation method for the pair-correlation function.

Journal Article↗
PubMed1997

Intersynaptic diffusion of neurotransmitter.

According to many theories of brain function, the computational power of the brain depends upon the number of independent synapses it contains. A synapse will not be independent if its receptors are activated or modified by neurotransmitter released at neighbouring synapses. Recently, there have been several reports suggesting the occurrence of 'crosstalk' or 'spillover', and a large number of results consistent with crosstalk. However, the quantitative importance of this phenomenon remains uncertain. We estimate the significance of crosstalk using a simple model which predicts that, during concentrated synaptic activity, crosstalk between distinct synapses is likely to activate high-affinity receptors and may also desensitize certain receptors. Comparison of these predictions with the experimental data highlights the information that is required for a more detailed model of crosstalk.

Animals↗
PubMed1990

On the measurement of particle number and mobility in nonideal solutions by fluorescence correlation spectroscopy.

Interparticle interactions are incorporated into the theoretical description of the initial amplitude, G(0), of the normalized fluorescence correlation spectroscopy autocorrelation function. Measurements of particle number, aggregate size, and interaction-dependent diffusion are then analyzed in the context of this generalized theory. It is shown that the neglect of interactions can introduce order-of-magnitude errors into estimates of particle number and aggregate size. It is also shown that measurement of G(0) provides an essentially unique method for testing the validity of theories of interaction-dependent membrane protein diffusion.

Mathematics↗
PubMed2003

Diffusion in a metallic melt at the critical temperature of mode coupling theory.

According to mode coupling theory, liquidlike motion becomes frozen at a critical temperature T(c) well above the caloric glass transition temperature T(g). Here, for the first time, we report on radiotracer diffusion in a supercooled Pd43Cu27Ni10P20 alloy from T(g) to the equilibrium melt. Liquidlike motion is seen to set in exactly above T(c) as evidenced by a gradual drop of the effective activation energy. This strongly supports the mode coupling scenario. Isotope effect measurements, which have never been carried out near T(c) in any material, show atomic transport up to the equilibrium melt to be far away from the hydrodynamic regime of uncorrelated binary collisions.

Journal Article↗
PubMed1985

Contribution of myocardial diffuse double-layer calcium to contractile function.

The role of diffuse double-layer calcium in cardiac excitation-contraction coupling was examined using rabbit interventricular septa, cultured neonatal rat myocardial cells, and gas-dissected sarcolemmal membranes. The diffuse double layer refers to the space directly adjacent to the sarcolemma where the ionic composition of the media is a direct function of the membrane surface potential. The divalent cation dimethonium was used as a specific probe for the diffuse double layer. According to Gouy-Chapman theory, replacement of sodium with sucrose should increase the amount of calcium located in this compartment. Dimethonium (10 mM) was found to decrease calcium uptake and contractility during low-sodium (33 mM) perfusion when the perfusate contained sucrose but not LiCl. Dimethonium did not decrease calcium uptake or contractility during control perfusion. The results suggest that calcium present in the myocardial diffuse double layer can be augmented or reduced in accordance with Gouy-Chapman theory. Changes in diffuse double-layer calcium are accompanied by small (7.8%) but significant changes in contractility.

Animals↗
PubMed1999

Transport of uterine PGF2 alpha to the ovaries by systemic circulation and local lymphovenous-arterial diffusion during luteolysis in sheep.

The theory of countercurrent vascular transfer of PGF2 alpha during luteolysis was examined. In the first experiment, pulmonary clearance of PGF2 alpha was determined to re-examine whether the total amount of PGF2 alpha was degraded in the lungs after one passage. Cardiac output was measured by the Fick method and PGF2 alpha by radio-immunoassay before and after vascular lung supply, using pulmonary catheterization and the interventional radiology method in ten anaesthetized ewes on day 16 of the oestrous cycle. Cardiac output remained stable (7156 +/- 439 ml min-1). Infusion of 5 iu oxytocin resulted in an increase in plasma PGF2 alpha concentrations at 30 min in the uterine vein and the pulmonary and femoral arteries (3811 +/- 806, 224 +/- 55 and 18 +/- 4 pg ml-1, respectively). The PGF2 alpha concentrations decreased exponentially and the half-time decreases were 27 (r = 0.99), 16 (r = 0.99) and 18 (r = 0.98) min, respectively. Pulmonary clearance of PGF2 alpha was estimated at 6338 +/- 451 ml min-1. In a second experiment, an arterio-arterial gradient of plasma PGF2 alpha concentrations was analysed between the proximal and distal segments of the ovarian artery to verify whether the total amount of PGF2 alpha flowing to the ovary was from the local venous-arterial countercurrent pathway. Surgical catheterization techniques were performed on 11 ewes on day 16 of the oestrous cycle. The ovarian arterial blood flow was measured by the implantable Doppler method (8 +/- 1 ml min-1). The maximum plasma PGF2 alpha concentrations in the femoral and distal ovarian arteries were 23 +/- 6 and 42 +/- 11 pg ml-1 (P < 0.05), respectively. Plasma PGF2 alpha decreased exponentially in the femoral artery and the half-time decrease was 26 min (r = 0.98), and in the distal ovarian artery close to the ovary PGF2 alpha decreased linearly and the half-time decrease was 108 min (r = 0.96). Consequently, the arterio-arterial diffusion gradient of PGF2 alpha concentrations was extended to 3 h. These experiments showed that the PGF2 alpha flow rate in the pulmonary artery was 42.275 +/- 10.793 micrograms per 150 min (n = 10) and the systemic arterial PGF2 alpha flow rate was 5.359 +/- 1.658 micrograms per 150 min (n = 10). Therefore, 12% of the PGF2 alpha was not oxidized by the lungs. The proximal ovarian PGF2 alpha flow rate was 6.909 +/- 2.341 ng per 150 min, while the distal flow rate was 21.003 +/- 5.703 ng per 150 min (n = 11). Thus, 33% of the PGF2 alpha was transported rapidly to the ovary via the systemic route, while 67% was transported by slow local countercurrent diffusion, which extended the duration of luteolytic activity to four times that of the PGF2 alpha surge. These results indicate both rapid systemic transport of PGF2 alpha to the ovaries and a slower buffer mechanism involving a local diffusion pathway, rather than a direct countercurrent system.

Animals↗