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Assar R.,Andrés Bello University | Assar R.,University of Chile | Montecino M.A.,Andrés Bello University | Montecino M.A.,15090007 Center for Genome Regulation | And 3 more authors.
BioSystems | Year: 2014

In order to describe the dynamic behavior of a complex biological system, it is useful to combine models integrating processes at different levels and with temporal dependencies. Such combinations are necessary for modeling acclimatization, a phenomenon where changes in environmental conditions can induce drastic changes in the behavior of a biological system. In this article we formalize the use of hybrid systems as a tool to model this kind of biological behavior. A modeling scheme called strong switches is proposed. It allows one to take into account both minor adjustments to the coefficients of a continuous model, and, more interestingly, large-scale changes to the structure of the model. We illustrate the proposed methodology with two applications: acclimatization in wine fermentation kinetics, and acclimatization of osteo-adipo differentiation system linking stimulus signals to bone mass. © 2014 Elsevier Ireland Ltd.

Assar R.,French Institute for Research in Computer Science and Automation | Assar R.,15090007 Center for Genome Regulation | Leisewitz A.V.,University of Santiago de Chile | Garcia A.,French Institute for Research in Computer Science and Automation | And 4 more authors.
BioSystems | Year: 2012

In order to treat osteoporosis and other bone mass disorders it is necessary to understand the regulatory processes that control the cell fate decisions responsible for going from bone precursor cells to bone tissue. Many processes interact to regulate cell division, differentiation and apoptosis. There are models for these basic processes, but not for their interactions. In this work we use the theory of switched systems, reuse and composition of validated models to describe the cell fate decisions leading to bone and fat formation. We describe the differentiation of osteo-adipo progenitor cells by composing its model with differentiation stimuli. We use the activation of the Wnt pathway as stimulus to osteoblast lineage, including regulation of cell division and apoptosis. This model is our first step to simulate physiological responses in silico to treatments for bone mass disorders. © 2012 Elsevier Ireland Ltd.

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