Cell death and life in cancer: mathematical modeling of cell fate decisions

Tumor development is characterized by a compromised balance between cell life and death decision mechanisms, which are tighly regulated in normal cells. Understanding this process provides insights for developing new treatments for fighting with cancer. We present a study of a mathematical model describing cellular choice between survival and two alternative cell death modalities: apoptosis and necrosis. The model is implemented in discrete modeling formalism and allows to predict probabilities of having a particular cellular phenotype in response to engagement of cell death receptors. Using an original parameter sensitivity analysis developed for discrete dynamic systems, we determine the critical parameters affecting cellular fate decision variables that appear to be critical in the cellular fate decision and discuss how they are exploited by existing cancer therapies

Platonic model of mind as an approximation to neurodynamics

Hierarchy of approximations involved in simplification of microscopic theories, from sub-cellural to the whole brain level, is presented. A new approximation to neural dynamics is described, leading to a Platonic-like model of mind based on psychological spaces. Objects and events in these spaces correspond to quasi-stable states of brain dynamics and may be interpreted from psychological point of view. Platonic model bridges the gap between neurosciences and psychological sciences. Static and dynamic versions of this model are outlined and Feature Space Mapping, a neurofuzzy realization of the static version of Platonic model, described. Categorization experiments with human subjects are analyzed from the neurodynamical and Platonic model points of view

Introduction to Focus Issue : Dynamics in Systems Biology

Peer reviewedPublisher PD

COMPUTER SIMULATION AND COMPUTABILITY OF BIOLOGICAL SYSTEMS

The ability to simulate a biological organism by employing a computer is related to the ability of the computer to calculate the behavior of such a dynamical system, or the "computability" of the system.* However, the two questions of computability and simulation are not equivalent. Since the question of computability can be given a precise answer in terms of recursive functions, automata theory and dynamical systems, it will be appropriate to consider it first. The more elusive question of adequate simulation of biological systems by a computer will be then addressed and a possible connection between the two answers given will be considered. A conjecture is formulated that suggests the possibility of employing an algebraic-topological, "quantum" computer (Baianu, 1971b) for analogous and symbolic simulations of biological systems that may include chaotic processes that are not, in genral, either recursively or digitally computable. Depending on the biological network being modelled, such as the Human Genome/Cell Interactome or a trillion-cell Cognitive Neural Network system, the appropriate logical structure for such simulations might be either the Quantum MV-Logic (QMV) discussed in recent publications (Chiara, 2004, and references cited therein)or Lukasiewicz Logic Algebras that were shown to be isomorphic to MV-logic algebras (Georgescu et al, 2001)

Using synchronous Boolean networks to model several phenomena of collective behavior

In this paper, we propose an approach for modeling and analysis of a number of phenomena of collective behavior. By collectives we mean multi-agent systems that transition from one state to another at discrete moments of time. The behavior of a member of a collective (agent) is called conforming if the opinion of this agent at current time moment conforms to the opinion of some other agents at the previous time moment. We presume that at each moment of time every agent makes a decision by choosing from the set {0,1} (where 1-decision corresponds to action and 0-decision corresponds to inaction). In our approach we model collective behavior with synchronous Boolean networks. We presume that in a network there can be agents that act at every moment of time. Such agents are called instigators. Also there can be agents that never act. Such agents are called loyalists. Agents that are neither instigators nor loyalists are called simple agents. We study two combinatorial problems. The first problem is to find a disposition of instigators that in several time moments transforms a network from a state where a majority of simple agents are inactive to a state with a majority of active agents. The second problem is to find a disposition of loyalists that returns the network to a state with a majority of inactive agents. Similar problems are studied for networks in which simple agents demonstrate the contrary to conforming behavior that we call anticonforming. We obtained several theoretical results regarding the behavior of collectives of agents with conforming or anticonforming behavior. In computational experiments we solved the described problems for randomly generated networks with several hundred vertices. We reduced corresponding combinatorial problems to the Boolean satisfiability problem (SAT) and used modern SAT solvers to solve the instances obtained

Joint perceptual decision-making: a case study in explanatory pluralism.

Traditionally different approaches to the study of cognition have been viewed as competing explanatory frameworks. An alternative view, explanatory pluralism, regards different approaches to the study of cognition as complementary ways of studying the same phenomenon, at specific temporal and spatial scales, using appropriate methodological tools. Explanatory pluralism has been often described abstractly, but has rarely been applied to concrete cases. We present a case study of explanatory pluralism. We discuss three separate ways of studying the same phenomenon: a perceptual decision-making task (Bahrami et al., 2010), where pairs of subjects share information to jointly individuate an oddball stimulus among a set of distractors. Each approach analyzed the same corpus but targeted different units of analysis at different levels of description: decision-making at the behavioral level, confidence sharing at the linguistic level, and acoustic energy at the physical level. We discuss the utility of explanatory pluralism for describing this complex, multiscale phenomenon, show ways in which this case study sheds new light on the concept of pluralism, and highlight good practices to critically assess and complement approaches

Revisiting the Complexity of Stability of Continuous and Hybrid Systems

We develop a framework to give upper bounds on the "practical" computational complexity of stability problems for a wide range of nonlinear continuous and hybrid systems. To do so, we describe stability properties of dynamical systems using first-order formulas over the real numbers, and reduce stability problems to the delta-decision problems of these formulas. The framework allows us to obtain a precise characterization of the complexity of different notions of stability for nonlinear continuous and hybrid systems. We prove that bounded versions of the stability problems are generally decidable, and give upper bounds on their complexity. The unbounded versions are generally undecidable, for which we give upper bounds on their degrees of unsolvability