Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “directional diffusion models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed2002

Bilateral overactivation of the sensorimotor cortex in the unilateral rodent model of Parkinson's disease - a functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) is used to investigate the basal ganglia (BG)-cortex circuit using a rat model of Parkinson's disease (PD). The model involves a unilateral destruction of the right substantia nigra by intranigral injection of the dopaminergic neurotoxin 6-hydroxydopamine. Volume of cortical activity was measured by the blood oxygenation level-dependent contrast method while applying electrical forepaw stimulation. The main findings are the following. (i) Contrary to the predictions of the classic model but in line with recent experimental results (positron emission tomography, fMRI and electrophysiology), an increased cortical activity in the sensorimotor cortex of PD rats compared with sham-operated or normal rats was found. (ii) A diffuse neuronal activity at large cortical areas that were not related directly to the stimulation used, was observed. (iii) No difference was found between the lesion and the nonlesion hemispheres when the left or the right forepaw was stimulated; both cortices show significant overactivation of the sensorimotor cortices in addition to diffuse cortical activation. The last finding could be explained by either corticocortical connections or by bilateral BG-cortex connections. These finding suggest that the mutual influence of the two hemispheres is important in the pathophysiology of the BG-cortex circuit and might be crucial in predicting treatments.

Animals↗
PubMed2002

Double-decker chemotaxis: no evidence for photonic stimulation of directed locomotion by human blood polymorphonuclear leukocytes.

The study was carried out under direct videomicroscopic control to ascertain whether electromagnetic forces (photons) can initiate directed cell motility of human polymorphonuclear neutrophils (PMN). Cell suspensions containing a mixture of randomly motile white blood cells and erythrocytes (red cells) were placed in a double-decked preparation created by a glass slide and two cover slips and sealed by paraffin. Erythrocytes in the upper or lower chamber were destroyed by a single burst from a narrow ruby laser beam. Directed locomotion of PMN toward the erythrocyte debris occurred exclusively in the chamber in which the erythrocytes had been destroyed. Only random PMN locomotion was observed in the adjacent chamber. The results indicate that in this experimental model, electromagnetic forces do not initiate directed locomotion.

Actin Cytoskeleton↗
PubMed1989

Sequential histopathologic changes in pancreaticoduodenal allograft rejection in dogs.

To determine the nature and sequence of the histologic changes in the early rejection of pancreaticoduodenal allografts and to assess the correlation between pancreaticoduodenal biopsy findings and the pathologic changes in the graft, we performed serial cystoscopically directed needle biopsies of pancreaticoduodenal allografts in 18 dogs and compared the findings with the histologic changes in 16 autografts as controls. Tissue adequate for evaluation was obtained by the biopsy technique in 70% of instances. The earliest and most characteristic manifestation of rejection was diffuse mixed inflammatory infiltrates involving the pancreatic acinar tissue and duodenum. The biopsy findings correlated well with the changes in the resected pancreatic specimens. Cellular rejection in the duodenum correlated with rejection in the pancreatic graft. There were no changes in the autografts that resembled cellular rejection. We conclude that, in the canine model, cystoscopically directed needle biopsy of pancreaticoduodenal allografts consistently provides adequate tissue for the diagnosis of rejection; the status of the graft can be monitored by serial biopsies of pancreatic acinar tissue and, possibly, by serial biopsies of the duodenal wall alone.

Animals↗
PubMed2005

Identification of an agonist-induced conformational change occurring adjacent to the ligand-binding pocket of the M(3) muscarinic acetylcholine receptor.

To study the conformational changes that convert G protein-coupled receptors (GPCRs) from their resting to their active state, we used the M(3) muscarinic acetylcholine receptor, a prototypical class A GPCR, as a model system. Specifically, we employed a recently developed in situ disulfide cross-linking strategy that allows the formation of disulfide bonds in Cys-substituted mutant M(3) muscarinic receptors present in their native membrane environment. At present, little is known about the conformational changes that GPCR ligands induce in the immediate vicinity of the ligand-binding pocket. To address this issue, we generated 11 Cys-substituted mutant M(3) muscarinic receptors and characterized these receptors in transfected COS-7 cells. All analyzed mutant receptors contained an endogenous Cys residue (Cys-532(7.42)) located within the exofacial segment of transmembrane domain (TM) VII, close to the agonist-binding site. In addition, all mutant receptors harbored a second Cys residue that was introduced into the exofacial segment of TM III, within the sequence Leu-142(3.27)-Asn-152(3.37). Disulfide cross-linking studies showed that muscarinic agonists, but not antagonists, promoted the formation of a disulfide bond between S151(3.36)C and Cys-532. A three-dimensional model of the inactive state of the M(3) muscarinic receptor indicated that Cys-532 and Ser-151 face each other in the center of the TM receptor core. Our cross-linking data therefore support the concept that agonist activation pulls the exofacial segments of TMs VII and III closer to each other. This structural change may represent one of the early conformational events triggering the more pronounced structural reorganization of the intracellular receptor surface. To the best of our knowledge, this is the first direct demonstration of a conformational change occurring in the immediate vicinity of the binding site of a GPCR activated by a diffusible ligand.

Amino Acid Sequence↗
PubMed1999

Steady-state enzyme kinetics in the Escherichia coli periplasm: a model of a whole cell biocatalyst.

This study provided analysis of in vivo enzyme kinetics in a model system which consisted of alkaline phosphatase in the periplasm of Escherichia coli. Modeling of complete substrate titration curves was achieved for a wide range of intraperiplasmic enzyme levels and outer membrane permeabilities. The results helped to identify the features most important to optimize in vivo reaction velocity. For many situations, a surprising finding was that maximum enzyme expression was not a major concern. For example, for moderate enzyme expression levels and moderate substrate levels (ca 0-5 mM), the limiting step for the enzyme in the periplasm was substrate (para-nitrophenylphosphate) diffusion through the outer membrane. In vivo reaction velocity was directly proportional to substrate concentration, outer membrane permeability, and the cell concentration. Velocity was also quite insensitive to a potent inhibitor of the enzyme. Even though diffusion-limited, periplasmic reaction velocity was quite sensitive to temperature, suggesting that the conformation of porin proteins in the E. coli outer membrane governed the average size of the pore. This model system therefore defined important features of bacterial whole cell biocatalyst design, which may also apply to other reactors using intact cells as catalysts.

Alkaline Phosphatase↗
PubMed1996

Current-voltage relations and steady-state characteristics of Na+-Ca2+ exchange: characterization of the eight-state consecutive transport model.

An analytical expression for Na+-Ca2+ exchange currents in cardiac cells has been obtained for an eight-state model. The equation obtained has been used to derive theoretical expressions for current-voltage relationships, maximum Na+-Ca2+ exchange currents, and half-saturating concentrations for Na+ and Ca2+. These equations were analyzed over a wide range of cytoplasmic and extracellular Na+ and Ca2+ concentrations, under forward and reverse "zero-trans" conditions. Correspondence of theoretical results with those obtained from giant excised patch experiments are presented. Rate constants from published reports were used to evaluate turnover rates for Na+-Ca2+ exchange in the forward and reverse directions. A factor, epsilon, is introduced that permits prediction of the extent to which the Na+-Ca2+ exchange cycle is under voltage or diffusion control. This factor can be conveniently used for data interpretation and comparison. The derived equations also provide a foundation for continuing experimental evaluation of the fidelity of this model.

Animals↗
PubMed1989

Renal handling of indomethacin: isolated membrane vesicles of proximal tubular cells as an in vitro model system for transport.

The indomethacin-transport properties of luminal and contraluminal membrane vesicles derived from dog renal proximal tubular cells were studied. In both membranes saturable sodium gradient-dependent transport of indomethacin, sensitive to probenecid, was observed. In luminal membrane vesicles uptake occurred predominantly by passive facilitated diffusion, whereas in contraluminal membrane vesicles, uptake was based upon both passive simple diffusion and active concentrative transport. As a result, indomethacin may accumulate in vivo in the tubular cells thereby exerting a direct nephrotoxic effect.

Animals↗
PubMedDate not supplied

A computational analysis of FXa generation by TF:FVIIa on the surface of rat vascular smooth muscle cells.

A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activation by the tissue factor-factor VIIa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared to previously obtained experimental data for the generation of factor Xa (FXa) by TF:VIIa on the surface of cultured rat vascular smooth muscle cells. In this study, the complete steady-state convection-diffusion equation was solved using the commercial software package, FLUENT (Fluent Inc., Lebanon, New Hampshire). A user-defined subroutine interfaced with FLUENT implemented the surface reaction which was modeled using classical Michaelis-Menten reaction kinetics. The numerical solutions were obtained for 12 cases which used combinations of three wall shear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ranged from classical kinetic reaction control (no dependence) to pure diffusional control (maximum dependence). The experimental data, however, were not represented by numerical data generated using a single reaction rate. The three numerically obtained fluxes which corresponded most closely to the experimental fluxes were determined using three different Vmax values. This finding supports the hypothesis that there may be a direct effect of flow on the TF:VIIa complex or the cell membrane.

Algorithms↗
PubMed1992

Extending the stochastic two-stage model of carcinogenesis to include self-regulation of the nonmalignant cell population.

One of the challenges of introducing greater biological realism into stochastic models of cancer induction is to find a way to represent the homeostatic control of the normal cell population over its own size without complicating the analysis too much to obtain useful results. Current two-stage models of carcinogenesis typically ignore homeostatic control. Instead, a deterministic growth path is specified for the population of "normal" cells, while the population of "initiated" cells is assumed to grow randomly according to a birth-death process with random immigrations from the normal population. This paper introduces a simple model of homeostatically controlled cell division for mature tissues, in which the size of the nonmalignant population remains essentially constant over time. Growth of the nonmalignant cell population (normal and initiated cells) is restricted by allowing cells to divide only to fill the "openings" left by cells that die or differentiate, thus maintaining the constant size of the nonmalignant cell population. The fundamental technical insight from this model is that random walks, rather than birth-and-death processes, are the appropriate stochastic processes for describing the kinetics of the initiated cell population. Qualitative and analytic results are presented, drawn from the mathematical theories of random walks and diffusion processes, that describe the probability of spontaneous extinction and the size distribution of surviving initiated populations when the death/differentiation rates of normal and initiated cells are known. The constraint that the nonmalignant population size must remain approximately constant leads to much simpler analytic formulas and approximations, flowing directly from random walk theory, than in previous birth-death models.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Death↗
PubMed2000

A unifying theory of refractive error development.

While retinal defocus is believed to be myopigenic in nature, the underlying mechanism has remained elusive. We recently constructed a theory of refractive error development to investigate its fundamental properties. Our Incremental Retinal-Defocus Theory is based on the principle that the change in retinal-defocus magnitude during an increment of genetically-programmed ocular growth provides the requisite sign for the appropriate alteration in subsequent environmentally-induced ocular growth. This theory was tested under five experimental conditions: lenses, diffusers, occlusion, crystalline lens removal, and prolonged nearwork. Predictions of the theory were consistent with previous animal and human experimental findings. In addition, simulations using a MATLAB/SIMULINK model supported our theory by demonstrating quantitatively the appropriate directional changes in ocular growth rate. Thus, our Incremental Retinal-Defocus Theory provides a simple and logical unifying concept underlying the mechanism for the development of refractive error.

Computer Simulation↗
PubMed2002

A model-based method for retrospective correction of geometric distortions in diffusion-weighted EPI.

The self-diffusion tensor may be calculated from several echo-planar image acquisitions preceded by different diffusion gradients. Unfortunately, these diffusion gradients cause geometric distortion that must be corrected before estimation of the tensor. In the present paper we suggest and implement a method for retrospective correction of these distortions firmly based on a physical model for the diffusion-weighted images. This method simultaneously estimates subject movement and distortion parameters by finding the set of parameters that minimizes residual error when fitting data to the diffusion tensor model. We show how this notion can be formalized as a quadratic form thereby facilitating the implementation of a rapid algorithm. In addition, we suggest models for how distortions vary with slice position and gradient direction that allow us to substantially reduce the dimensionality of the parameter space. Our results indicate that we are able to estimate both eddy current-induced distortion and subject movement directly from the data without need of any additional measurements.

Algorithms↗
PubMed2002

Statistical analysis of the influence of conspecifics on the dispersal of a soil collembola.

The evidence for dispersal activity among soil-living invertebrates comes mainly from observations of their movement on artificial substrates or of colonisation of defaunated soils in the field. In an attempt to elucidate the dispersal pattern of soil collembolans in the presence of conspecifics, statistical analyses were undertaken to describe and simulate the movement of groups of Onychiurus armatus released in trays of homogeneous soil. A chi(2) test was used to reject the null hypothesis that individuals moved independently of each other and uniformly in all directions. The mean radial distance moved (1-2 cm day(-1)) and the radial standard deviation varied temporally and with the density of conspecifics. To capture the interaction between the moving individuals, four dispersal models (pure diffusion, diffusion with drift interaction, drift interaction and synchronised diffusion, and drift interaction and behavioural mood), were formulated as stochastic differential equations. The parameters of the models were estimated by minimising the deviance between the observed replicates and replicates that were simulated using the models. The dynamics of movement were best described by modelling the drift interaction as dependent on whether individuals were in a social or an asocial mood.

Animal Migration↗
PubMed1987

Recombination by resolvase is inhibited by lac repressor simultaneously binding operators between res sites.

The Tn3 resolvase requires that the two recombination (res) sites be aligned as direct repeats on the same molecule for efficient recombination to occur. To test whether resolvase must contact the DNA between res sites as predicted by tracking models, we have determined the sensitivity of recombination to protein diffusion blockades. Recombination between two res sites is unaffected either by lac repressor or bacteriophage T7 RNA polymerase being bound between them. Yet recombination is inhibited by lac repressor if the res site is bounded by a lac operator on both sides. We demonstrate that lac repressor will bind to more than one DNA site under the conditions used to assay recombination. This result suggests that lac repressor can inhibit resolvase by forming a DNA loop that isolates a res site topologically. These results do not support a tracking model for resolvase but suggest that the structure and topology of the DNA substrate is important in the formation of a synapse between res sites.

Binding Sites↗
PubMed1981

Fluorescence photobleaching recovery in solutions of labeled actin.

We have demonstrated that the technique of fluorescence photobleaching recovery (FPR) can be used to examine the state of a single component in complex self-assembling macromolecular systems. Polymerization of actin, initiated by addition of salt or Mg+2 to a low-ionic-strength solution of G-actin, has been observed by sequential measurement of FPR with the aid of fluorescein-labeled actin. Solutions of actin which had been labeled using 5-iodoacetamido fluorescein (5-IAF) showed anomalous recovery of fluorescence above the initial value, which indicates a photoinduced increase in local polymerization. No such anomaly was observed with actin that had been labeled with fluorescein isothiocyanate (FITC). The FPR data are directly interpretable in terms of the fraction of labeled protein that is immobilized in the supramolecular assembly and in terms of the average diffusion coefficient of the mobile fraction. Our data are consistent with the "treadmill" model of actin polymerization, in that they show that actin is present under polymerizing conditions either as a high polymer or as monomer or low oligomer. We believe that the FPR technique can be applied to the study of many types of reconstituted motile or cytoskeletal systems in vitro or in vivo.

Actins↗
PubMed1997

A triphasic analysis of negative osmotic flows through charged hydrated soft tissues.

Osmotic flow and ion transport in a one-dimensional steady diffusion process through charged hydrated soft tissues such as articular cartilage were analysed using the triphasic theory (Lai et al., 1991, J. biomech. Engng 113, 245-258). It was found that solvent would flow from the high NaCl concentration side to the low concentration side (i.e. negative osmosis) when the fixed charge density within the tissue (or membrane) separating the two electrolyte (NaCl) solutions was lower than a critical value. The condition for negative osmosis was derived based on a linear version of the triphasic theory. Distributions of ion concentration and strain field within the tissue were calculated numerically. Quantitative results of osmotic flow rates (ordinary and negative osmosis), ion flux and electric potential across the tissue during this diffusion process suggest that the negative osmosis phenomenon is due to the friction between ions and water since they could flow through the tissues at different rates and different directions.

Biomechanical Phenomena↗
PubMedDate not supplied

Noisy spiking neurons and networks: useful approximations for firing probabilities and global behavior.

Electrophysiological properties of spiking neurons receiving complex stimuli perturbed by noise are investigated. A semi-analytical estimate of firing probabilities and subthreshold behavior of the stochastic system can be made in terms of the solution of a purely deterministic system. The method comes from an approximation for the distribution function and moments of the underlying non linear multidimensional diffusion process. This so called moment method works for general conductance-based systems and an application is presented for the Hodgkin-Huxley neuronal model. Statistical properties obtained from the moment method are compared with direct numerical integration of the stochastic system. The firing probability due to external noise is derived as a closed formula. Results are given for different forms of the deterministic component of the stimulus. A generalization to neural networks of conductance-based systems with internal currents perturbed by noise can be obtained using the same approach. In the case of fully connected networks, a mean field population equation is derived which may be compared to Kuramoto's master equation for weakly coupled neural oscillators.

Action Potentials↗
PubMed2003

DTI mapping of human brain connectivity: statistical fibre tracking and virtual dissection.

Several approaches have been used to trace axonal trajectories from diffusion MRI data. If such techniques were first developed in a deterministic framework reducing the diffusion information to one single main direction, more recent approaches emerged that were statistical in nature and that took into account the whole diffusion information. Based on diffusion tensor MRI data coming from normal brains, this paper presents how brain connectivity could be modelled globally by means of a random walk algorithm. The mass of connections thus generated was then virtually dissected to uncover different tracts. Corticospinal, corticobulbar, and corticothalamic tracts, the corpus callosum, the limbic system, several cortical association bundles, the cerebellar peduncles, and the medial lemniscus were all investigated. The results were then displayed in the form of an in vivo brain connectivity atlas. The connectivity pattern and the individual fibre tracts were then compared to known anatomical data; a good matching was found.

Algorithms↗
PubMed2006

The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends.

The microtubule cytoskeleton is a dynamic structure in which the lengths of the microtubules are tightly regulated. One regulatory mechanism is the depolymerization of microtubules by motor proteins in the kinesin-13 family. These proteins are crucial for the control of microtubule length in cell division, neuronal development and interphase microtubule dynamics. The mechanism by which kinesin-13 proteins depolymerize microtubules is poorly understood. A central question is how these proteins target to microtubule ends at rates exceeding those of standard enzyme-substrate kinetics. To address this question we developed a single-molecule microscopy assay for MCAK, the founding member of the kinesin-13 family. Here we show that MCAK moves along the microtubule lattice in a one-dimensional (1D) random walk. MCAK-microtubule interactions were transient: the average MCAK molecule diffused for 0.83 s with a diffusion coefficient of 0.38 microm2 s(-1). Although the catalytic depolymerization by MCAK requires the hydrolysis of ATP, we found that the diffusion did not. The transient transition from three-dimensional diffusion to 1D diffusion corresponds to a "reduction in dimensionality" that has been proposed as the search strategy by which DNA enzymes find specific binding sites. We show that MCAK uses this strategy to target to both microtubule ends more rapidly than direct binding from solution.

Adenosine Triphosphate↗