| 1. |
- Cho, Kwang-Hyun, et al.
(författare)
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A hybrid systems framework for cellular processes
- 2005
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Ingår i: Biosystems (Amsterdam. Print). - : Elsevier BV. - 0303-2647 .- 1872-8324. ; 80:3, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- With the availability of technologies that allow us to obtain stimulus-response time series data for modeling and system identification, there is going to be an increasing need for conceptual frameworks in which to formulate and test hypotheses about intra- and inter-cellular dynamics, in general and not just dependent on a particular cell line, cell type, organism, or technology. While the semantics can be quite different, biologists and systems scientists use in many cases a similar language (notion of feedback, regulation, etc.). A more abstract system-theoretic framework for signals, systems, and control could provide the biologist with an interface between the domains. Apart from recent examples to identify functional elements and describing them in engineering terms, there have been various more abstract developments to describe dynamics at the cell level in the past. This includes Rosen's (M,R)-systems. This paper presents an abstract and general compact mathematical framework of intracellular dynamics, regulation and regime switching inspired by (M,R)-theory and based on hybrid automata.
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| 2. |
- Frey, Simone, et al.
(författare)
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How quantitative measures unravel design principles in multi-stage phosphorylation cascades.
- 2008
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Ingår i: Journal of theoretical biology. - : Elsevier BV. - 1095-8541 .- 0022-5193. ; 254:1, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- We investigate design principles of linear multi-stage phosphorylation cascades by using quantitative measures for signaling time, signal duration and signal amplitude. We compare alternative pathway structures by varying the number of phosphorylations and the length of the cascade. We show that a model for a weakly activated pathway does not reflect the biological context well, unless it is restricted to certain parameter combinations. Focusing therefore on a more general model, we compare alternative structures with respect to a multivariate optimization criterion. We test the hypothesis that the structure of a linear multi-stage phosphorylation cascade is the result of an optimization process aiming for a fast response, defined by the minimum of the product of signaling time and signal duration. It is then shown that certain pathway structures minimize this criterion. Several popular models of MAPK cascades form the basis of our study. These models represent different levels of approximation, which we compare and discuss with respect to the quantitative measures.
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