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1.
Comput Biol Med ; 61: 75-91, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25864166

RESUMO

This paper employs the root locus method to conduct a detailed investigation of the parameter regions that ensure bistability in a well-studied gene regulatory network namely, lac operon of Escherichia coli (E. coli). In contrast to previous works, the parametric bistability conditions observed in this study constitute a complete set of necessary and sufficient conditions. These conditions were derived by applying the root locus method to the polynomial equilibrium equation of the lac operon model to determine the parameter values yielding the multiple real roots necessary for bistability. The lac operon model used was defined as an ordinary differential equation system in a state equation form with a rational right hand side, and it was compatible with the Hill and Michaelis-Menten approaches of enzyme kinetics used to describe biochemical reactions that govern lactose metabolism. The developed root locus method can be used to study the steady-state behavior of any type of convergent biological system model based on mass action kinetics. This method provides a solution to the problem of analyzing gene regulatory networks under parameter uncertainties because the root locus method considers the model parameters as variable, rather than fixed. The obtained bistability ranges for the lac operon model parameters have the potential to elucidate the appearance of bistability for E. coli cells in in vivo experiments, and they could also be used to design robust hysteretic switches in synthetic biology.


Assuntos
Escherichia coli/genética , Redes Reguladoras de Genes/fisiologia , Genes Bacterianos/fisiologia , Óperon Lac/fisiologia , Modelos Genéticos
2.
IEEE Trans Neural Netw ; 14(4): 891-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-18238068

RESUMO

A method to store each element of an integral memory set M subset {1,2,...,K}/sup n/ as a fixed point into a complex-valued multistate Hopfield network is introduced. The method employs a set of inequalities to render each memory pattern as a strict local minimum of a quadratic energy landscape. Based on the solution of this system, it gives a recurrent network of n multistate neurons with complex and symmetric synaptic weights, which operates on the finite state space {1,2,...,K}/sup n/ to minimize this quadratic functional. Maximum number of integral vectors that can be embedded into the energy landscape of the network by this method is investigated by computer experiments. This paper also enlightens the performance of the proposed method in reconstructing noisy gray-scale images.

3.
IEEE Trans Neural Netw ; 11(4): 851-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-18249813

RESUMO

The key point in design of radial basis function networks is to specify the number and the locations of the centers. Several heuristic hybrid learning methods, which apply a clustering algorithm for locating the centers and subsequently a linear leastsquares method for the linear weights, have been previously suggested. These hybrid methods can be put into two groups, which will be called as input clustering (IC) and input-output clustering (IOC), depending on whether the output vector is also involved in the clustering process. The idea of concatenating the output vector to the input vector in the clustering process has independently been proposed by several papers in the literature although none of them presented a theoretical analysis on such procedures, but rather demonstrated their effectiveness in several applications. The main contribution of this paper is to present an approach for investigating the relationship between clustering process on input-output training samples and the mean squared output error in the context of a radial basis function netowork (RBFN). We may summarize our investigations in that matter as follows: 1) A weighted mean squared input-output quantization error, which is to be minimized by IOC, yields an upper bound to the mean squared output error. 2) This upper bound and consequently the output error can be made arbitrarily small (zero in the limit case) by decreasing the quantization error which can be accomplished through increasing the number of hidden units.

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