Showing papers by "David A. Kessler published in 2006"

FDA Regulation of Stem-Cell–Based Therapies

Abstract: The authors review existing regulations regarding cell and tissue products and discuss how they expect the Food and Drug Administration to apply these regulations to scientists' efforts to develop and test stem-cell–based therapies.

Directional sensing in eukaryotic chemotaxis: A balanced inactivation model

Abstract: Many eukaryotic cells, including Dictyostelium discoideum amoebae, fibroblasts, and neutrophils, are able to respond to chemoattractant gradients with high sensitivity. Recent studies have demonstrated that, after the introduction of a chemoattractant gradient, several chemotaxis pathway components exhibit a subcellular reorganization that cannot be described as a simple amplification of the external gradient. Instead, this reorganization has the characteristics of a switch, leading to a well defined front and back. Here, we propose a directional sensing mechanism in which two second messengers are produced at equal rates. The diffusion of one of them, coupled with an inactivation scheme, ensures a switch-like response to external gradients for a large range of gradient steepness and average concentration. Furthermore, our model is able to reverse the subcellular organization rapidly, and its response to multiple simultaneous chemoattractant sources is in good agreement with recent experimental results. Finally, we propose that the dynamics of a heterotrimeric G protein might allow for a specific biochemical realization of our model.

Analytic approach to the evolutionary effects of genetic exchange

Abstract: We present an approximate analytic study of our previously introduced model of evolution including the effects of genetic exchange. This model is motivated by the process of bacterial transformation. We solve for the velocity, the rate of increase of fitness, as a function of the fixed population size, $N$. We find the velocity increases with ln $N$, eventually saturating at an $N$ which depends on the strength of the recombination process. The analytical treatment is seen to agree well with direct numerical simulations of our model equations.

Fluctuation-induced instabilities in front propagation up a comoving reaction gradient in two dimensions.

Abstract: We study two-dimensional (2D) fronts propagating up a comoving reaction rate gradient in finite number reaction-diffusion systems. We show that in a 2D rectangular channel, planar solutions to the deterministic mean-field equation are stable with respect to deviations from planarity. We argue that planar fronts in the corresponding stochastic system, on the other hand, are unstable if the channel width exceeds a critical value. Furthermore, the velocity of the stochastic fronts is shown to depend on the channel width in a simple and interesting way, in contrast to fronts in the deterministic mean-field equation. Thus fluctuations alter the behavior of these fronts in an essential way. These effects are shown to be partially captured by introducing a density cutoff in the reaction rate. Moreover, some of the predictions of the cutoff mean-field approach are shown to be in quantitative accord with the stochastic results.

Equation-free dynamic renormalization of a Kardar-Parisi-Zhang-type equation.

Abstract: In the context of equation-free computation, we devise and implement a procedure for using short-time direct simulations of a Kardar-Parisi-Zhang-(KPZ-) type equation to calculate the self-similar solution for its ensemble averaged correlation function. The method involves "lifting" from candidate pair-correlation functions to consistent realization ensembles, short bursts of KPZ-type evolution, and appropriate rescaling of the resulting averaged pair correlation functions. Both the self-similar shapes and their similarity exponents are obtained at a computational cost significantly reduced to that required to reach saturation in such systems.

Front propagation dynamics with exponentially-distributed hopping

Abstract: We study reaction-diffusion systems where diffusion is by jumps whose sizes are distributed exponentially. We first study the Fisher-like problem of propagation of a front into an unstable state, as typified by the A+B → 2A reaction. We find that the effect of fluctuations is especially pronounced at small hopping rates. Fluctuations are treated heuristically via a density cutoff in the reaction rate. We then consider the case of propagating up a reaction rate gradient. The effect of fluctuations here is pronounced, with the front velocity increasing without limit with increasing bulk particle density. The rate of increase is faster than in the case of a reaction-gradient with nearest-neighbor hopping. We derive analytic expressions for the front velocity dependence on bulk particle density. Computer simulations are performed to confirm the analytical results.