N G van Kampen 1981 Amsterdam: North-Holland xiv + 419 pp price Dfl 180 This is a book which, at a lower price, could be expected to become an essential part of the library of every physical scientist concerned with problems involving fluctuations and stochastic processes, as well as those who just enjoy a beautifully written book. It provides an extensive graduate-level introduction which is clear, cautious, interesting and readable.

https://iopscience.iop.org/article/10.1088/0031-9112/34/4/040/pdf

Stochastic Processes in Physics and Chemistry

/pdf/robustness-metrics-consolidating-the-multiple-approaches-to-3zac9ihiqa.pdf

Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

Multimodal oncological strategies which combine chemotherapy or radiotherapy with hyperthermia, have a potential of improving the efficacy of the non-surgical methods of cancer treatment Hyperthermia engages the heat-shock response (HSR) mechanism, the main component of which are heat-shock proteins Cancer cells have already partially activated HSR, thereby hyperthermia may be more toxic to them relative to normal cells On the other hand, HSR triggers thermotolerance, ie hyperthermia-treated cells show an impairment in their susceptibility to a subsequent heat-induced stress This poses questions about efficacy and optimal strategy for anti-cancer therapy combined with hyperthermia treatment To address these questions, we adapt our previous HSR model and propose its stochastic extension We formalize the notion of a HSP-induced thermotolerance Next, we estimate the intensity and the duration of the thermotolerance Finally, we quantify the effect of a multimodal therapy based on hyperthermia and a cytotoxic effect of bortezomib, a clinically approved proteasome inhibitor Consequently, we propose an optimal strategy for combining hyperthermia and proteasome inhibition modalities In summary, by a mathematical analysis of HSR, we are able to support the common belief that the combination of cancer treatment strategies increases therapy efficacy

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2013.0527

Modelling the efficacy of hyperthermia treatment.

Despite a conceptually simple mechanism of signaling, the JAK-STAT pathway exhibits considerable behavioral complexity. Computational pathway models are tools to investigate in detail signaling process. They integrate well with experimental studies, helping to explain molecular dynamics and to state new hypotheses, most often about the structure of interactions.

A relatively small amount of experimental data is available for a JAK1/2-STAT1 variant of the pathway, hence, only several computational models were developed. Here we review a dominant approach of kinetic modeling of the JAK1/2-STAT1 pathway, based on ordinary differential equations. We also give a brief overview of attempts to computationally infer topology of this pathway.

/pdf/computational-models-of-the-jak1-2-stat1-signaling-1tnio25ic0.pdf

Computational models of the JAK1/2-STAT1 signaling

As suggested by the origin of the word, sphingolipids are mysterious molecules with various roles in antagonistic cellular processes such as autophagy, apoptosis, proliferation and differentiation. Moreover, sphingolipids have recently been recognized as important messengers in cellular signaling pathways. Notably, sphingolipid metabolism disorders have been observed in various pathological conditions such as cancer and neurodegeneration. The existing formal models of sphingolipid metabolism focus mainly on de novo ceramide synthesis or are limited to biochemical transformations of particular subspecies. Here, we propose the first comprehensive computational model of sphingolipid metabolism in human tissue. Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles. The model that we present here was validated using recently proposed methods of model analysis, allowing to detect the most sensitive and experimentally non-identifiable parameters and determine the main sources of model variance. Moreover, we demonstrate the usefulness of our model in the study of molecular processes underlying Alzheimer’s disease, which are associated with sphingolipid metabolism.

/pdf/computational-modeling-of-sphingolipid-metabolism-333vpbm83w.pdf

Computational modeling of sphingolipid metabolism

Modeling the dynamic behavior of signal transduction pathways is an important topic in systems biology. Mathematical models complement experimental technologies used to identify the molecular components and interactions in a system of interest. In this paper, we illustrate different types of mathematical approaches that are used to model signaling network behavior. Here, we review the basic methods of sensitivity analysis and apply them to the model of the system of membrane receptors. Four such receptors are considered: growth factor epidermal, low density lipoprotein, transferrin and vitellogenin receptor. We argue that application of sensitivity analysis methods provides an insight into how a signaling system controls the cell behavior.

/pdf/sensitivity-analysis-of-mathematical-models-of-signalling-bq8xdh96yp.pdf

A. Nalecz

Papers

Sensitivity analysis of mathematical models of signalling pathways