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- A Crudu, A Debussche, A Muller, O Radulescu
- 2011

We study the asymptotic behavior of multiscale stochastic gene networks using weak limits of Markov jump processes. Depending on the time and concentration scales of the system we distinguish four types of limits: continuous piecewise deterministic processes (PDP) with switching, PDP with jumps in the continuous variables, averaged PDP, and PDP with… (More)

The variation in the expression patterns of the gap genes in the blastoderm of the fruit fly Drosophila melanogaster reduces over time as a result of cross regulation between these genes, a fact that we have demonstrated in an accompanying article in PLoS Biology (see Manu et al., doi:10.1371/journal.pbio.1000049). This biologically essential process is an… (More)

- Manu, Svetlana Surkova, Alexander V Spirov, Vitaly V Gursky, Hilde Janssens, Ah-Ram Kim +5 others
- PLoS biology
- 2009

Developing embryos exhibit a robust capability to reduce phenotypic variations that occur naturally or as a result of experimental manipulation. This reduction in variation occurs by an epigenetic mechanism called canalization, a phenomenon which has resisted understanding because of a lack of necessary molecular data and of appropriate gene regulation… (More)

BACKGROUND
Cellular processes such as metabolism, decision making in development and differentiation, signalling, etc., can be modeled as large networks of biochemical reactions. In order to understand the functioning of these systems, there is a strong need for general model reduction techniques allowing to simplify models without loosing their main… (More)

BACKGROUND
Stochastic simulation of gene networks by Markov processes has important applications in molecular biology. The complexity of exact simulation algorithms scales with the number of discrete jumps to be performed. Approximate schemes reduce the computational time by reducing the number of simulated discrete events. Also, answering important… (More)

The concept of limiting step gives the limit simplification: the whole network behaves as a single step. This is the most popular approach for model simplification in chemical kinetics. However, in its simplest form this idea is applicable only to the simplest linear cycles in steady states. For such the simplest cycles the nonstation-ary behaviour is also… (More)

We use the Litvinov-Maslov correspondence principle to reduce and hybridize networks of biochemical reactions. We apply this method to a cell cycle oscillator model. The reduced and hybridized model can be used as a hybrid model for the cell cycle. We also propose a practical recipe for detecting quasi-equilibrium QE reactions and quasi-steady state QSS… (More)

We introduce a methodology allowing to reduce and to compare systems biology models. This is based on several reduction tools. The first tool is a combination of Clarke's graphical technique and idempotent algebra. The second tool is the Karhunen-Lò eve expansion, providing a linear embedding for the invariant manifold. The nonlinear dimension of the… (More)

The concept of the limiting step is extended to the asymptotology of multiscale reaction networks. Complete theory for linear networks with well separated reaction rate constants is developed. We present algorithms for explicit approximations of eigenvalues and eigenvectors of kinetic matrix. Accuracy of estimates is proven. Performance of the algorithms is… (More)

We advocate the use of qualitative models in the analysis of large biological systems. We show how qualitative models are linked to theoretical differential models and practical graphical models of biological networks. A new technique for analyzing qualitative models is introduced, which is based on an efficient representation of qualitative systems. As… (More)