Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity

Background\ud \ud The transition from premalignant to invasive tumour growth is a prolonged multistep process governed by phenotypic adaptation to changing microenvironmental selection pressures. Cancer prevention strategies are required to interrupt or delay somatic evolution of the malignant invasive phenotype. Empirical studies have consistently demonstrated that increased physical activity is highly effective in reducing the risk of breast cancer but the mechanism is unknown.\ud \ud Results\ud \ud Here we propose the hypothesis that exercise-induced transient systemic acidosis will alter the in situ tumour microenvironment and delay tumour adaptation to regional hypoxia and acidosis in the later stages of carcinogenesis. We test this hypothesis using a hybrid cellular automaton approach. This model has been previously applied to somatic evolution on epithelial surfaces and demonstrated three phases of somatic evolution, with cancer cells escaping in turn from the constraints of limited space, nutrient supply and waste removal. In this paper we extend the model to test our hypothesis that transient systemic acidosis is sufficient to arrest, or at least delay, transition from in situ to invasive cancer.\ud \ud Conclusions\ud \ud Model simulations demonstrate that repeated episodes of transient systemic acidosis will interrupt critical evolutionary steps in the later stages of carcinogenesis resulting in substantial delay in the evolution to the invasive phenotype. Our results suggest transient systemic acidosis may mediate the observed reduction in cancer risk associated with increased physical activity

On the blockage problem and the non-analyticity of the current for the parallel TASEP on a ring

The Totally Asymmetric Simple Exclusion Process (TASEP) is an important example of a particle system driven by an irreversible Markov chain. In this paper we give a simple yet rigorous derivation of the chain stationary measure in the case of parallel updating rule. In this parallel framework we then consider the blockage problem (aka slow bond problem). We find the exact expression of the current for an arbitrary blockage intensity $\varepsilon$ in the case of the so-called rule-184 cellular automaton, i.e. a parallel TASEP where at each step all particles free-to-move are actually moved. Finally, we investigate through numerical experiments the conjecture that for parallel updates other than rule-184 the current may be non-analytic in the blockage intensity around the value $\varepsilon = 0$

Cellular automata and spin chains: a medium range connection

A cellular automaton is an extremely simple physical system: it has both a discrete time and space dimension. While they were initially developed as a new paradigm for quantum computation, it was soon realized that cellular automata were able to display very interesting behaviours like integrability and large-scale diffusive transport. Indeed rule 54, an elementary cellular automaton, is widely considered the simplest physical system to display integrability, making it the perfect toy model to study various properties of classical and quantum integrability and how they connect. Since a cellular automaton is a fully discrete system it is natural to ask what is the corresponding model in the continuum, if it exists. Recently a new algebraic framework was developed that made it possible to generate classes of integrable quantum spin chains with medium range interactions while also building their corresponding discretization, in the form of quantum cellular automata. In this work we will study what it means for an system to be integrable, both in the classical and quantum realm; then we will describe the structure behind cellular automata and we will show the connection between integrable spin chains and quantum cellular automata. Finally we will try to extend this framework to a more complex system, the class of Restricted Solid-on-Solid models

Boolean Delay Equations: A simple way of looking at complex systems

Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time. They represent therewith metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit multiple equilibria and limit cycles, as well as more complex, fractal solution sets, such as Devil's staircases and ``fractal sunbursts``. All known solutions of dissipative BDEs have stationary variance. BDE systems of this type, both free and forced, have been used as highly idealized models of climate change on interannual, interdecadal and paleoclimatic time scales. BDEs are also being used as flexible, highly efficient models of colliding cascades in earthquake modeling and prediction, as well as in genetics. In this paper we review the theory of systems of BDEs and illustrate their applications to climatic and solid earth problems. The former have used small systems of BDEs, while the latter have used large networks of BDEs. We moreover introduce BDEs with an infinite number of variables distributed in space (``partial BDEs``) and discuss connections with other types of dynamical systems, including cellular automata and Boolean networks. This research-and-review paper concludes with a set of open questions.Comment: Latex, 67 pages with 15 eps figures. Revised version, in particular the discussion on partial BDEs is updated and enlarge