Adaptive Multi-Scale Model Simulation, Reduction and Integration for Cardiac Muscle Physiology

Principal Investigator
James B. Bassingthwaighte (Bioengineering), Howard M. Chizeck, Hong Qian (Bioengineering), Les E. Atlas

Sponsor(s)
National Science Foundation (NSF)

Award Period
08/15/2005 - 07/31/2008

Abstract
An objective of this project is to develop a novel approach to carrying out simulations with continuous monitoring and dynamic control of the computing carried out at subsidiary modules. The continuous monitoring and dynamic control concept is based on established approaches from electrical engineering. This project has six specific aims: (1) To define a representative multi-scale biological system (namely, the cardio-respiratory-skeletal muscle system for oxygen exchange and substrate delivery) at five levels of scale, defining explicit modules for the subsidiary models at each level. (2) To describe models mathematically, to write computer code, to verify the code, and to validate the models against high quality data for all components at each level of this 5-tiered model, using the full set of equations for each component at each level. (3) To define computationally simpler, reduced forms of the mathematical models for components at each level. These reduced form models must accurately match the behavior of the full models (for the components of interest, at that level) over a prescribed range of conditions. (4) To devise algorithms for detecting when the reduced model forms begin to lose accuracy because of changes in conditions (external or internal), and to devise and implement mechanisms for either resorting to the use of the full subsidiary model or shifting to an alternative form of the reduced model. The goal is automated reconfiguration of the model when changes in conditions occur. (5) To combine the algorithms and software developed in for Aims 1-4, into a documented and tested software package. This is the central product of the project, providing examples of all of the techniques in a form that can be applied to different multi-scale modeling applications, and can be used by other investigators. (6). To disseminate the strategies and technologies for the multi-scale methods, to provide an archive for the code in which these methods are implemented, and to provide the source code for the biological models and algorithms that are developed.

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