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Displaying: 3 Found: 20 Total: 69


Computational model of the cAMP-mediated sensory response and calcium-dependent adaptation in vertebrate olfactory receptor neurons


Description

Computational model of the cAMP-mediated sensory response and calcium-dependent adaptation in vertebrate olfactory receptor neurons

Model Status

This model runs in both OpenCell and COR and the units are consistent. The model recreates results from a sinlge pulse experiment suitable for adaptation and oscillatory behavior. Modification of the stimulus and addition of IX, an intermediate Ca2+ generated substance can be made to fulfill different simulations.

Model Structure

Abstract: We develop a mechanistic mathematical model of the G-protein coupled signaling pathway responsible for generating current responses in frog olfactory receptor neurons. The model incorporates descriptions of ligand-receptor interaction, intracellular transduction events involving the second messenger cAMP, effector ion-channel activity, and calcium-mediated feedback steps. We parameterized the model with respect to suction pipette current recordings from single cells stimulated with multiple odor concentrations. The proposed model accurately predicts the receptor-current response of the neuron to brief and prolonged odorant exposure and is able to produce the adaptation observed under repeated or sustained stimulation.

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Full-scale model of glycolysis in Saccharomyces cerevisiae


Description

ABSTRACT: We present a powerful, general method of fitting a model of a biochemical pathway to experimental substrate concentrations and dynamical properties measured at a stationary state, when the mechanism is largely known but kinetic parameters are lacking. Rate constants and maximum velocities are calculated from the experimental data by simple algebra without integration of kinetic equations. Using this direct approach, we fit a comprehensive model of glycolysis and glycolytic oscillations in intact yeast cells to data measured on a suspension of living cells of Saccharomyces cerevisiae near a Hopf bifurcation, and to a large set of stationary concentrations and other data estimated from comparable batch experiments. The resulting model agrees with almost all experimentally known stationary concentrations and metabolic fluxes, with the frequency of oscillation and with the majority of other experimentally known kinetic and dynamical variables. The functional forms of the rate equations have not been optimized.

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HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time


Description

ABSTRACT: A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t 1/2 = 1.6 days), and plasma virions were estimated to have a mean life-span of 0.3 days (t 1/2 = 0.24 days). The estimated average total HIV-1 production was 10.3 x 10(9) virions per day, which is substantially greater than previous minimum estimates. The results also suggest that the minimum duration of the HIV-1 life cycle in vivo is 1.2 days on average, and that the average HIV-1 generation time--defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles--is 2.6 days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also theoretical principles to guide the development of treatment strategies.

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