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using a mechanistic model of lipoprotein metabolism and kinetics. CPT Pharmacomet. Syst. Pharmacol. 2015,
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28. Bassingthwaighte, J.B.; Chizeck, H.J.; Atlas, L.E. Strategies and tactics in multiscale modeling of cell-to-organ
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29. Ménochet, K.; Kenworthy, K.E.; Houston, J.B.; Galetin, A. Simultaneous assessment of uptake and metabolism
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30. Gao, W.; Jusko, W.J. Modeling disease progression and rosiglitazone intervention in type 2 diabetic
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31. Bowyer, J.; Zhao, J.; Rosser, S.; Colloms, S.; Bates, D. Development and experimental validation of a
mechanistic model of in vitro DNA recombination. In Proceedings of the 2015 37th Annual International
Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milano, Italy, 25–29 August 2015.
32. Feola, A.J.; Myers, J.G.; Raykin, J.; Mulugeta, L.; Nelson, E.S.; Samuels, B.C.; Ethier, C.R. Finite element
modeling of factors influencing optic nerve head deformation due to intracranial pressure. Investig. Ophthal.
Vis. Sci. 2016, 57, 1901–1911. [CrossRef][PubMed]
33. Smith, A.K.; Petersen, B.K.; Ropella, G.E.P.; Kennedy, R.C.; Kaplowitz, N.; Ookhtens, M.; Hunt, C.A.
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34. Linderman, J.J.; Cilfone, N.A.; Pienaar, E.; Gong, C.; Kirschner, D.E. A multi-scale approach to designing
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35. Issad, T.; Malaterre, C. Are dynamic mechanistic explanations still mechanistic? In Explanation in Biology:
An Enquiry into the Diversity of Explanatory Patterns in the Life Sciences; Braillard, P.A., Malaterre, C., Eds.;
Dordrecht, The Netherland, 2015; pp. 265–292.
36. Schoeberl, B.; Pace, E.A.; Fitzgerald, J.B.; Harms, B.D.; Xu, L.; Nie, L.; Linggi, B.; Kalra, A.; Paragas, V.;
Bukhalid, R.; et al. Therapeutically targeting ErbB3: A key node in ligand-induced activation of the ErbB
receptor-PI3K axis. Sci. Signal 2009, 2, ra31. [CrossRef][PubMed]
37. Hosseini, I.; Mac Gabhann, F. Mechanistic Models Predict Efficacy of CCR5-Deficient Stem Cell Transplants
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38. Moreno, J.D.; Zhu, Z.I.; Yang, P.-C.; Bankston, J.R.; Jeng, M.-T.; Kang, C.; Wang, L.; Bayer, J.D.; Christini, D.J.;
Trayanova, N.A.; et al. A computational model to predict the effects of class I anti-arrhythmic drugs on
ventricular rhythms. Sci. Transl. Med. 2011, 3, ra83. [CrossRef][PubMed]
39. Bentley, K.; Gerhardt, H.; Bates, P.A. Agent-based simulation of notch-mediated tip cell selection in
angiogenic sprout initialisation. J. Theor. Biol. 2009, 250, 25–36. [CrossRef][PubMed]
40. Tang, J.; Hunt, C.A. Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion.
PLoS Comput. Biol. 2010, 6, e1000681. [CrossRef][PubMed]
41. Cockrell, C.; Christley, S.; An, G. Investigation of inflammation and tissue patterning in the gut using a
spatially explicit general-purpose model of enteric tissue (SEGMEnT). PLOS Comput. Biol. 2014, 10, e1003507.
[CrossRef][PubMed]
42. Scherer, C.; Jeltsch, F.; Grimm, V.; Blaum, N. Merging trait-based and individual-based modelling: An animal
functional type approach to explore the responses of birds to climatic and land use changes in semi-arid
African savannas. Ecol. Mod. 2016, 24, 75–89. [CrossRef]
43. Weisel, E.W.; Petty, M.D.; Mielke, R.R. Validity of models and classes of models in semantic composability. In
Proceedings of the Fall 2003 Simulation Interoperability Workshop, Orlando, FL, USA, 14–19 September 2003.
44. Yankeelov, T.E.; An, G.; Saut, O.; Luebeck, E.G.; Popel, A.S.; Ribba, B.; Vicini, P.; Zhou, X.; Weis, J.A.;
Ye, K.; Genin, G.M. Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success.
Ann. Biomed. Eng. 2016, 44, 2626–2641. [CrossRef][PubMed]
202
26. Meier-Schellersheim, M.; Fraser, I.D.; Klauschen, F. Multiscale modeling for biologists. WIREs: Syst. Biol. Med.
2009, 1, 4–14. [CrossRef][PubMed]
27. Lu, J.; Cleary, Y.; Maugeais, C.; Kiu Weber, C.I.; Mazer, N.A. Analysis of “on/off” kinetics of a CETP inhibitor
using a mechanistic model of lipoprotein metabolism and kinetics. CPT Pharmacomet. Syst. Pharmacol. 2015,
4, 465–473. [CrossRef][PubMed]
28. Bassingthwaighte, J.B.; Chizeck, H.J.; Atlas, L.E. Strategies and tactics in multiscale modeling of cell-to-organ
systems. Proc. IEEE 2006, 94, 819–831. [CrossRef][PubMed]
29. Ménochet, K.; Kenworthy, K.E.; Houston, J.B.; Galetin, A. Simultaneous assessment of uptake and metabolism
in rat hepatocytes: A comprehensive mechanistic model. J. Pharmacol. Exp. Therap. 2012, 341, 2–15. [CrossRef]
[PubMed]
30. Gao, W.; Jusko, W.J. Modeling disease progression and rosiglitazone intervention in type 2 diabetic
Goto-Kakizaki rats. J. Pharmacol. Exp. Therap. 2012, 341, 617–625. [CrossRef][PubMed]
31. Bowyer, J.; Zhao, J.; Rosser, S.; Colloms, S.; Bates, D. Development and experimental validation of a
mechanistic model of in vitro DNA recombination. In Proceedings of the 2015 37th Annual International
Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milano, Italy, 25–29 August 2015.
32. Feola, A.J.; Myers, J.G.; Raykin, J.; Mulugeta, L.; Nelson, E.S.; Samuels, B.C.; Ethier, C.R. Finite element
modeling of factors influencing optic nerve head deformation due to intracranial pressure. Investig. Ophthal.
Vis. Sci. 2016, 57, 1901–1911. [CrossRef][PubMed]
33. Smith, A.K.; Petersen, B.K.; Ropella, G.E.P.; Kennedy, R.C.; Kaplowitz, N.; Ookhtens, M.; Hunt, C.A.
Competing Mechanistic hypotheses of acetaminophen-induced hepatotoxicity challenged by virtual
experiments. PLoS Comput. Biol. 2016.[ CrossRef][PubMed]
34. Linderman, J.J.; Cilfone, N.A.; Pienaar, E.; Gong, C.; Kirschner, D.E. A multi-scale approach to designing
therapeutics for tuberculosis. Integr. Biol. 2015, 7, 591–609. [CrossRef][PubMed]
35. Issad, T.; Malaterre, C. Are dynamic mechanistic explanations still mechanistic? In Explanation in Biology:
An Enquiry into the Diversity of Explanatory Patterns in the Life Sciences; Braillard, P.A., Malaterre, C., Eds.;
Dordrecht, The Netherland, 2015; pp. 265–292.
36. Schoeberl, B.; Pace, E.A.; Fitzgerald, J.B.; Harms, B.D.; Xu, L.; Nie, L.; Linggi, B.; Kalra, A.; Paragas, V.;
Bukhalid, R.; et al. Therapeutically targeting ErbB3: A key node in ligand-induced activation of the ErbB
receptor-PI3K axis. Sci. Signal 2009, 2, ra31. [CrossRef][PubMed]
37. Hosseini, I.; Mac Gabhann, F. Mechanistic Models Predict Efficacy of CCR5-Deficient Stem Cell Transplants
in HIV Patient Populations. CPT Pharmacomet. Syst. Pharmacol. 2016, 5, 82–90. [CrossRef][PubMed]
38. Moreno, J.D.; Zhu, Z.I.; Yang, P.-C.; Bankston, J.R.; Jeng, M.-T.; Kang, C.; Wang, L.; Bayer, J.D.; Christini, D.J.;
Trayanova, N.A.; et al. A computational model to predict the effects of class I anti-arrhythmic drugs on
ventricular rhythms. Sci. Transl. Med. 2011, 3, ra83. [CrossRef][PubMed]
39. Bentley, K.; Gerhardt, H.; Bates, P.A. Agent-based simulation of notch-mediated tip cell selection in
angiogenic sprout initialisation. J. Theor. Biol. 2009, 250, 25–36. [CrossRef][PubMed]
40. Tang, J.; Hunt, C.A. Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion.
PLoS Comput. Biol. 2010, 6, e1000681. [CrossRef][PubMed]
41. Cockrell, C.; Christley, S.; An, G. Investigation of inflammation and tissue patterning in the gut using a
spatially explicit general-purpose model of enteric tissue (SEGMEnT). PLOS Comput. Biol. 2014, 10, e1003507.
[CrossRef][PubMed]
42. Scherer, C.; Jeltsch, F.; Grimm, V.; Blaum, N. Merging trait-based and individual-based modelling: An animal
functional type approach to explore the responses of birds to climatic and land use changes in semi-arid
African savannas. Ecol. Mod. 2016, 24, 75–89. [CrossRef]
43. Weisel, E.W.; Petty, M.D.; Mielke, R.R. Validity of models and classes of models in semantic composability. In
Proceedings of the Fall 2003 Simulation Interoperability Workshop, Orlando, FL, USA, 14–19 September 2003.
44. Yankeelov, T.E.; An, G.; Saut, O.; Luebeck, E.G.; Popel, A.S.; Ribba, B.; Vicini, P.; Zhou, X.; Weis, J.A.;
Ye, K.; Genin, G.M. Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success.
Ann. Biomed. Eng. 2016, 44, 2626–2641. [CrossRef][PubMed]
202