This proposal is for the 22nd to 26th years of the National Simulation Resource (NSR) in Circulatory Mass Transport at the University of Washington (UW). It concerns metabolic transformations and exchanges. It builds the concepts and modeling of intracellular events on top of the previously developed models, modeling systems and expertise on convection-diffusion-permeation-reaction systems. The five-year program will produce models from subcellular to whole-organ level for the inflow of substrates and humoral agents, the exchange across capillary and cell membranes, the metabolic transformations and the washout of metabolites. There are three scientific Sections and a set of Cores. Investigators from Vanderbilt, McGill, and Michigan State Universities contribute subcontractual projects. Investigators in 13 other universities and 4 countries contribute collaborative projects. There are 26 project leaders and 65 project investigators.Section D.I. concerns five developments in fundamental tools for Simulation Analysis in metabolic and humoral systems. The first is a major development of JSIM, a Java-based, integrative model simulation system designed for easy and collaborative model development. It improves upon the previous XSIM environment which was limited to Unix systems. New tools will be provided for simulating transport in complex geometries, for modeling of stochastic systems, for the application of biochemical circuit theory, and for databasing and modeling with a markup language. Section D.II. has three subsections (fifteen projects) defining particular modeling targets for UW on Whole-organ Transport, CellularTransport, Metabolism and Control, and Stochastic Cellular and Molecular Processes. Section D.III. consists of fourteen collaborative projects on Cardiac Flows and Metabolism, Cardiac Receptor Activity, Nucleoside and Nucleotide Regulation, Cellular Energetics, Cardiac Coronary Anatomy, and Cardiac Contraction and Metabolism. Section D.IV. provides core support for software development, simulation and modeling analysis, training, and the dissemination of NSR deliverables.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SSS-H (02))
Program Officer
Peng, Grace
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University of Washington
Biomedical Engineering
Schools of Engineering
United States
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Bassingthwaighte, James B; Raymond, Gary M; Dash, Ranjan K et al. (2016) The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion: The Pathway for Oxygen. Adv Exp Med Biol 876:103-110
Raymond, G M; Bassingthwaighte, J B (2015) Diverse Data Sets Can Yield Reliable Information through Mechanistic Modeling: Salicylic Acid Clearance. Br J Pharm Res 7:457-476
Jardine, Bartholomew; Bassingthwaighte, James B (2013) Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation. Am J Physiol Lung Cell Mol Physiol 305:L42-55
Alessio, Adam M; Bassingthwaighte, James B; Glenny, Robb et al. (2013) Validation of an axially distributed model for quantification of myocardial blood flow using ¹³N-ammonia PET. J Nucl Cardiol 20:64-75
Bassingthwaighte, James B; Chinn, Tamara M (2013) Reexamining Michaelis-Menten enzyme kinetics for xanthine oxidase. Adv Physiol Educ 37:37-48
Bassingthwaighte, James B; Beard, Daniel A; Carlson, Brian E et al. (2012) Modeling to link regional myocardial work, metabolism and blood flows. Ann Biomed Eng 40:2379-98
Alessio, Adam M; Butterworth, Erik; Caldwell, James H et al. (2010) Quantitative imaging of coronary blood flow. Nano Rev 1:
Dash, Ranjan K; Bassingthwaighte, James B (2010) Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 38:1683-701
Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20
Chizeck, Howard Jay; Butterworth, Erik; Bassingthwaighte, James B (2009) Error detection and unit conversion. IEEE Eng Med Biol Mag 28:50-8

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