Publications by authors named "David G Schaeffer"

Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.

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Background: The cyclic AMP-Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved signal transduction mechanism that regulates cellular growth and differentiation in animals and fungi. We present a mathematical model that recapitulates the short-term and long-term dynamics of this pathway in the budding yeast, Saccharomyces cerevisiae. Our model is aimed at recapitulating the dynamics of cAMP signaling for wild-type cells as well as single (pde1Δ and pde2Δ) and double (pde1Δpde2Δ) phosphodiesterase mutants.

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Instabilities in cardiac dynamics have been widely investigated in recent years. One facet of this work has studied chaotic behavior, especially possible correlations with fatal arrhythmias. Previously chaotic behavior was observed in various models, specifically in the breakup of spiral and scroll waves.

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Cardiac restitution has been described both in terms of ionic models-systems of ODE's-and in terms of mapping models. While the former provide a more fundamental description, the latter are more flexible in trying to fit experimental data. Recently we proposed a two-dimensional mapping that accurately reproduces restitution behavior of a paced cardiac patch, including rate dependence and accommodation.

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It is known, from both experiments and simulations, that cardiac action potentials are shortened near a non-conducting boundary. In the present paper, this effect is studied in a simple, two-current ionic model, with propagation restricted to a 1D fibre. An asymptotic approximation for the dependence of action potential duration on distance to the boundary is derived.

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If spatial extent is neglected, ionic models of cardiac cells consist of systems of ordinary differential equations (ODEs) which have the property of excitability, i.e., a brief stimulus produces a prolonged evolution (called an action potential in the cardiac context) before the eventual return to equilibrium.

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Unlike classical bifurcations, border-collision bifurcations occur when, for example, a fixed point of a continuous, piecewise C1 map crosses a boundary in state space. Although classical bifurcations have been much studied, border-collision bifurcations are not well understood. This paper considers a particular class of border-collision bifurcations, i.

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We investigate, both experimentally and theoretically, the period-doubling bifurcation to alternans in heart tissue. Previously, this phenomenon has been modeled with either smooth or border-collision dynamics. Using a modification of existing experimental techniques, we find a hybrid behavior: Very close to the bifurcation point, the dynamics is smooth, whereas further away it is border-collision-like.

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Various authors have shown that, near the onset of a period-doubling bifurcation, small perturbations in the control parameter may result in much larger disturbances in the response of the dynamical system. Such amplification of small signals can be measured by a gain defined as the magnitude of the disturbance in the response divided by the perturbation amplitude. In this paper, the perturbed response is studied using normal forms based on the most general assumptions of iterated maps.

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Many features of the sequence of action potentials produced by repeated stimulation of a patch of cardiac muscle can be modeled by a 1D mapping, but not the full behavior included in the restitution portrait. Specifically, recent experiments have found that (i) the dynamic and S1-S2 restitution curves are different (rate dependence) and (ii) the approach to steady state, which requires many action potentials (accommodation), occurs along a curve distinct from either restitution curve. Neither behavior can be produced by a 1D mapping.

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We study the uniformly weighted ensemble of force balanced configurations on a triangular network of nontensile contact forces. For periodic boundary conditions corresponding to isotropic compressive stress, we find that the probability distribution for single-contact forces decays faster than exponentially. This superexponential decay persists in lattices diluted to the rigidity percolation threshold.

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Restitution, the characteristic shortening of action potential duration (APD) with increased heart rate, has been studied extensively because of its purported link to the onset of fibrillation. Restitution is often represented in the form of mapping models where APD is a function of previous diastolic intervals (DIs) and/or APDs, A(n+1)=F(D(n),A(n),D(n-1),A(n-1),..

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Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting the onset of abnormal cardiac rhythms. However, it is known that different pacing protocols lead to different APD restitution curves (RCs). This phenomenon, known as APD rate dependence, is a consequence of memory in the tissue.

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In this paper we introduce and study a model for electrical activity of cardiac membrane which incorporates only an inward and an outward current. This model is useful for three reasons: (1) Its simplicity, comparable to the FitzHugh-Nagumo model, makes it useful in numerical simulations, especially in two or three spatial dimensions where numerical efficiency is so important. (2) It can be understood analytically without recourse to numerical simulations.

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