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Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed mechanistic understanding of the complex underlying network remains elusive. We have translated here the current knowledge of the molecular mechanisms of the(More)
BACKGROUND Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1), the proinflammatory cytokine Tumor Necrosis Factor (TNF) activates pro-apoptotic signaling via caspase(More)
— In this paper we consider the question of parameter identifiability for biochemical reaction networks, as typically encountered in systems biology. Specifically, we are interested in deriving conditions on the biochemical reaction network and on the measured outputs that guarantee identifiability of the parameters. Taking the specific system structure of(More)
Signal transduction networks are complex, as are their mathematical models. Gaining a deeper understanding requires a system analysis. Important aspects are the number, location and stability of steady states. In particular, bistability has been recognised as an important feature to achieve molecular switching. This paper compares different model structures(More)
Signal transduction is the process by which the cell converts one kind of signal or stimulus into another. This involves a sequence of biochemical reactions, carried out by proteins. The dynamic response of complex cell signalling networks can be modelled and simulated in the framework of chemical kinetics. The mathematical formulation of chemical kinetics(More)
Recently, Bagci et al. (1) proposed a mathematical model of the mitochon-drial apoptotic pathway. In their study, they also investigated the robustness of different simplified signalling models with respect to parameter changes. They found that bistability achieved via cooperative ultrasensitivity is " much more robust " than other mechanisms such as(More)
Preamble The use of new technology and mathematics to study the systems of nature is one of the most significant scientific trends of the century. Driven by the need for more precise scientific understand, advances in automated measurement are providing rich new sources of biological and physiological data. This data provides information with which to(More)
Biological reaction networks consist of many substances and reactions between them. Like many other biological systems, they have a modular structure. Therefore, a division of a biological reaction network into smaller units highly facilitates its investigation. The authors propose an algorithm to divide an ordinary differential equation (ODE) model of a(More)
— Apoptosis is a programmed cell death by which the organism removes unwanted cells. Its core reactions can be described by a system of differential equations exhibiting multiple steady-states. In this paper we analyse how this model can include both very slow dynamics for the lag phase before apoptosis (in theory up to several days) while the apoptosis(More)