O Wolkenhauer

..Some reflections on Robert Rosen, Chu and Ho, and Louie...

..Rather, theorem proving, in conjunction with conventional mathematical (mechanistic) modeling, is an essential tool for a deeper understanding in systems biology...

..To elucidate the molecular action of IFNγ, we have established a mathematical model of STAT1 activation and combined experimental studies with computer simulations...

..Beyond a critical analysis of existing models, we furthermore investigated the question how adjacent metabolic pathways, for instance photorespiration, can be integrated in such models...

..acetobutylicum to be optimized and exploited on an industrial scale, the effect of pH-induced gene regulation on solvent production by C. acetobutylicum in continuous culture must be understood as fully as possible...

..Despite of the apparent importance of signal amplification, there have been few attempts to formalise this concept...

..The multikinase inhibitor Sorafenib has antitumor activity in solid tumors and its effects on acute lymphoblastic leukemia (ALL) cells are still unclear...

..Also, for genomic scans they often need to be incorporated in detection workflows using custom scripts, which decreases transparency and reproducibility...

..What we are seeking here is a conceptual framework to demonstrate how the "fate" of intestinal crypts is an emergent property that inherently arises from the complex yet robust underlying biology of stem cells...

..Simulations can mimic living systems, but they are not like living systems...

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..g. Michaelis-Menten type models), as well as algorithms to estimate steady-states. The robustness and sensitivity of the models can also be analysed and visualized by computing the power-law's logarithmic gains and sensitivities...

..Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory...

..Using tools of control systems analysis, as embodied in the disciplines of systems biology, similar predictive modelling/simulation studies are now bearing fruit in cell signalling research...

..Using simple examples, we show how biochemical reactions are modelled in the dynamic systems framework and visualized using block-diagrams...

..Our model effectively demonstrates how data, acquired with an optical microscope, can be processed and used for a systems biology analysis of signal transduction pathways...

..The aim is to provide a concise set of MATLAB functions that encourage the experimentation with systems biology models. All the script files are available from www.sbi.uni-rostock.de/ publications_matlab-paper.html...

..As a result, a 'family tree' for stochastic models in systems biology is sketched, providing explicit derivations of their formal relationship and clarifying assumptions involved...

..Throughout the text, two pedagogical examples are used to key illustrate ideas. With extensive references to the literature, our goal is to clarify key concepts and thereby prepare the reader for more advanced texts...

..This is explained through multiple resettings of M-phase promoting factor (MPF), caused by the coupling between mean and (co)variance, near the G2/M transition...

..The relation between models and data is discussed in this chapter. Thereby, we focus on the requirements on experimental data from the perspective of systems biology projects...

..Furthermore, intracellular processes, like receptor internalization, do manipulate the level of stimulus such that level and duration of the stimulus is conducive to characteristic behavior...

..Several authors have suggested in recent times that dimerisation relates to a series of physical and biological outcomes used by the cell in the regulation of signal transduction...

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..These case studies reveal modelling as a tool to increase the understanding of complex systems, to help formulating hypotheses and to guide the design of more directed experiments that test predictions...

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..We discuss the potential for computer-aided mathematical modeling of biological systems in medical research with examples from some of the major therapeutic areas: cancer, cardiovascular, diabetic and neurodegenerative medicine...

..We show how these approximations simplify the mathematical treatment of biochemical networks but we also demonstrate differences between the complete system and its approximations with respect to the transient and steady state behavior...

..Metabolic control coefficients do not reliably detect all thresholds and suffer from false positives...

..The second model describes Hes1 repression by the protein complex Gro/TLE1/Hes1, where Gro/TLE1 is activated by Hes1 phosphorylation. Finally, we discuss our analytical and numerical results in relation to experimental data...

..Here, we summarize findings from cell culture experiments, animal models and studies of patients with Alzheimer's disease. Furthermore, we discuss pharmacological interactions and computational methods for risk assessment...

..We, furthermore, show the use of such a methodology in a case study, analyzing receptor and transcription factor modulation affecting the responsiveness of the JAK2/STAT5 pathway...

..Moreover, the interplay between DNA damage and 14-3-3σ may induce bistability in the oscillation of p53...

..6. The hesitant stance of the pharmaceutical industry towards major investment in systems biology research has to be addressed. 7. Leading medical journals should be encouraged to promote mathematical modelling...

..In particular, the investigation on the effects of signal inhibition and feedback loops and the validation of structural hypotheses are discussed...

..In addition, our results propose that unphosphorylated or serine-phosphorylated STAT1 can act as transcription factors of MUC4, either alone by progressive binding to different sites in the promoter or both together...

..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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..We believe that further investigations into mathematical modelling of the STAT1 pathway will improve the understanding of the antifibrotic interferon action...

..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...

..sbtoolbox.org. The website also contains a tutorial, extensive documentation and examples...

..The proposed system-theoretic approach is expected to be further applicable to predict the signaling behavior of NF-kappaB in a quantitative manner for any variation of the ligand, TNFalpha...

..The results of our study justified the theoretical basis of the weighted resampling approach, which clearly outperforms the others...

..As a consequence, the distribution of the intensity of the pixels is usually negatively skewed. This asymmetry results in a larger displacement for the mean and median than for the mode from the ideal situation mentioned above...

..The performance was evaluated with a measure for internal cluster correlation and the geometrical properties of the clusters, showing that the FCV-TSD algorithm had better performance than the k -means algorithm on both datasets...

..This review guides through all steps in the cDNA microarray data analysis pipeline and gives a basic understanding of the challenges in interpreting large microarray datasets...

..With few sampling time points feasible, their selection is of practical importance in experimental design. Finally, the theoretical results are supported with an application...

..Finally, we propose an experiment design methodology, which is not limited by the amount of parameter perturbations, and illustrate its use with an in numero example...

..The simulations demonstrate how the apparently paradoxical behavior can emerge as a result of cellular conditions...

..In particular, a favoured gap of 7 for Leu is found in coiled coils. Our method contributes to the characterization of whole sequences by extracting and quantifying stable stochastic features...

..Microarray technology allows us to generate large sets of time series data and is, therefore, discussed with regard to its use in mathematical modelling of gene expression and regulation...

..In the last section we formulate when, according to us, in biology (and in systems biology in particular), it should be said that a system (process) is stable, and when it is structurally stable...