Abstract
We introduce biomimetic in silico devices, and means for validation along with methods for testing and refining them. The devices are constructed from adaptable software components designed to map logically to biological components at multiple levels of resolution. In this report we focus on the liver; the goal is to validate components that mimic features of the lobule (the hepatic primary functional unit) and dynamic aspects of liver behavior, structure, and function. An assembly of lobule-mimetic devices represents an in silico liver. We validate against outflow profiles for sucrose administered as a bolus to isolated, perfused rat livers. Acceptable in silico profiles are experimentally indistinguishable from those of the in situ referent. This new technology is intended to provide powerful new tools for challenging our understanding of how biological functional units function in vivo.
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Roberts, M., Magnusson, B., Burczynski, F., Weiss, M.: Enterohepatic Circulation: Physiological, Pharmacokinetic and Clinical Implications. Clin. Pharmacokinet 41, 751–790 (2002)
Noble, D.: The Rise of Computational Biology. Nat. Rev. Mol. Cell. Bio. 3, 460–463 (2002)
Noble, D.: The Future: Putting Humpty-Dumpty Together Again. Biochem. Soc. Transact. 31, 156–158 (2003)
Roberts, M.S., Anissimov, Y.G.: Modeling of Hepatic Elimination and Organ Distribution Kinetics with the Extended Convection-Dispersion Model. J. Pharmacokin. Biopharm. 27, 343–382 (1999)
Hung, D.Y., Chang, P., Weiss, M., Roberts, M.S.: Structure-Hepatic Disposition Relationships for Cationic Drugs in Isolated Perfused Rat Livers: Transmembrane Exchange and Cytoplasmic Binding Process. J. Pharmacol. Exper. Therap. 297, 780–789 (2001)
Falkenhainer, B., Forbus, K.D.: Compositional Modeling: Finding the Right Model for the Job. Art. Intel. 51, 95–143 (1991)
Santini, S., Jain, R.: Similarity Measures. IEEE Tran. Pattern Analysis and Machine Intelligence 21, 871–883 (1999)
Teutsch, H.F., Schuerfeld, D., Groezinger, E.: Three-Dimensional Reconstruction of Parenchymal Units in the Liver of the Rat. Hepatology 29, 494–505 (1999)
Burns, A., Davies, G.: Concurrent Programming, pp. 1–2. Addison-Wesley, Reading (1993)
Sanchez, S.M., Lucas, T.W.: Exploring the World of Agent-Based Simulations: Simple Models, Complex Analyses. In: Yücesan, E., Chen, C.-H., Snowdon, J.L., Charnes, C.M. (eds.) Proceedings of the 2002 Winter Simulation Conference, pp. 116–126 (2002)
Gumucio, J.J., Miller, D.L.: Zonal Hepatic Function: Solute-Hepatocyte Interactions Within the Liver Acinus. Prog. Liver Diseases 7, 17–30 (1982)
Tyson, J.J., Chen, K., Novak, B.: Network Dynamics and Cell Physiology. Nat. Revs. Mol. Cell Biol. 2, 908–917 (2001)
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© 2005 Springer-Verlag Berlin Heidelberg
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Hunt, C.A., Ropella, G.E.P., Roberts, M.S., Yan, L. (2005). Biomimetic in Silico Devices. In: Danos, V., Schachter, V. (eds) Computational Methods in Systems Biology. CMSB 2004. Lecture Notes in Computer Science(), vol 3082. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-25974-9_4
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DOI: https://doi.org/10.1007/978-3-540-25974-9_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-25375-4
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