Received (Day Month Year) Revised (Day Month Year) Accepted (Day Month Year) p16 is recognised as a tumor suppressor gene due to the prevalence of its genetic inactivation in all types of human cancers. Additionally, p16 gene plays a critical role in controlling aging, regulating cellular senescence, detection and maintenance of DNA damage. The molecular mechanism behind these events involves p16-mediated signalling pathway (or p16-Rb pathway), the focus of our study. Understanding functional dependence between dynamic behavior of biological components involved in the p16-mediated pathway and aforesaid molecular-level events might suggest possible implications in the diagnosis, prognosis and treatment of human cancer.In the present work we employ reverse-engineering approach to construct the most detailed computational model of p16-mediated pathway in higher eukaryotes. We implement experimental data from the literature to validate the model, and under various assumptions predict the dynamic behavior of p16 and other biological components by interpreting the simulation results. The quantitative model of p16-mediated pathway is created in a systematic manner in terms of Petri net technologies.

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In this work we use hybrid Petri nets to create a model of the p16-mediated signaling pathway in higher eukaryotes and conduct its stochastic simulation-based validation by wet lab observations available from literature. The validation is conducted in terms of stochastic simulations with respect to the wild-type p16 protein and its mutated form. Our model catches the behavior of the major molecular regulators of the p16-mediated signaling pathway in wild-type cells as well as when DNA damage is detected or replicative senescence occurs. We observe that the stochastic model predicts some characteristics of the underlying pathway more clearly, evidently and perspicuously compared to the deterministic model, enriching the breadth and the quality of the outcome.

How to cite this article: Güran M, Akçay Nİ. Hand hygiene as an incomplete challenge for developing countries: discussions based on knowledge and perceptions of nurses in North Cyprus example and published studies.

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