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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)
Recently, a mathematical model of the mitochondrial apo-ptotic pathway was proposed. In that study, the robustness of different simplified signaling models with respect to parameter changes was also investigated. It was found that bistability achieved via cooperative ultrasensitivity is ''much more robust'' than other mechanisms such as inhibitor(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)
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)
Bistable dynamical switches are frequently encountered in mathematical modeling of biological systems because binary decisions are at the core of many cellular processes. Bistable switches present two stable steady-states, each of them corresponding to a distinct decision. In response to a transient signal, the system can flip back and forth between these(More)