Mechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse. Multiple data sources might be required, and data may not be in a uniform or (...) desirable format. We describe a calibration strategy to address the challenges of scarcity and heterogeneity of calibration data. Our strategy focuses on parameters whose initial values cannot be easily derived from the literature, and our goal is to determine the values of these parameters via calibration with constraints set by relevant data. When combined with a covariance matrix adaptation evolution strategy, this step-by-step approach can be applied to a wide range of biological models. We describe a stepwise, integrative and iterative approach to multiscale mechanistic model calibration, and provide an example of calibrating a pathophysiological lung adenocarcinoma model. Using the approach described here we illustrate the successful calibration of a complex knowledge-based mechanistic model using only the limited heterogeneous datasets publicly available in the literature. (shrink)

Contains papers from a November 1995 conference held in Eastern Europe, celebrating the centenary of the Lvov-Warsaw school of analytic philosophy. Papers deal with all directions of research undertaken by Polish analytic philosophers. Special attention is paid to logic and comparisons with other philosophical movements, particularly with brentanism. Contains sections on history and comparisons, the ideas of Lesniewski, philosophy of language, logic and the foundations of mathematics, logic and philosophy, and the ontology, epistemology, and philosophy of science. No index. Annotation (...) copyrighted by Book News, Inc., Portland, OR. (shrink)