Boolean network-based model of the Bcl-2 family mediated MOMP regulation

Mitochondrial outer membrane permeabilization (MOMP) is one of the most important points, in majority of apoptotic signaling cascades. Decision mechanism controlling whether the MOMP occurs or not, is formed by an interplay between members of the Bcl-2 family. To understand the role of individual members of this family within the MOMP regulation, we constructed a boolean network-based mathematical model of interactions between the Bcl-2 proteins. Results of computational simulations reveal the existence of the potentially malign configurations of activities of the Bcl-2 proteins, blocking the occurrence of MOMP, independently of the incoming stimuli. Our results suggest role of the antiapoptotic protein Mcl-1 in relation to these configurations. We demonstrate here, the importance of the Bid and Bim according to activation of effectors Bax and Bak, and the irreversibility of this activation. The model further shows the distinct requirements for effectors activation, where the antiapoptic protein Bcl-w is seemingly a key factor preventing the Bax activation. We believe that this work may help to describe the functioning of the Bcl-2 regulation of MOMP better, and hopefully provide some contribution regarding the anti-cancer drug development research

Crowd simulation for dynamic environments based on information spreading and agents’ personal interests

In this work a novel crowd simulation framework that incorporates information of the dynamic environment is introduced. It supports knowledge spreading and allows the simulated agents to behave according to their personal needs that are affected by the surroundings. Each agent has their own personal interests and needs, which affects its goals and interactions with the environment. Genetic algorithms are used to simulate the dynamic behaviour of the environment and the knowledge spreading. As a result more accurate and realistic simulations are obtained improving a wide range of industrial and research applications that require accurate crowd simulation and modelling

Issues in the philosophical foundations of lexical semantics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Linguistics and Philosophy, 1993.Includes bibliographical references (leaves 152-159).by Brian Edward Ulicny.Ph.D