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Oxford, UK, 2007.
6.
Illari, P.M.; Williamson, J. What is a mechanism? Thinking about mechanisms across the sciences. European.
J. Philos. Sci. 2012, 2, 119–135. [CrossRef]
7.
Merriam-Webster Unabridged. Available online: http://unabridged.merriam-webster.com/ (accessed on
2 October 2016).
8.
Craver, C.F. When mechanistic models explain. Synthese 2006, 153, 355–376. [CrossRef]
9.
Darden, L. Thinking again about biological mechanisms. Philos. Sci. 2009, 75, 958–969. [CrossRef]
10. Miyakawa, K.; Albee, R.; Letzig, L.G.; Lehner, A.F.; Scott, M.A.; Buchweitz, J.P.; James, L.P.; Ganey, P.E.;
Roth, R.A. A Cytochrome P450–independent mechanism of acetaminophen-induced injury in cultured
mouse hepatocytes. J. Pharmacol. Exp. Therap. 2015, 354, 230–237. [CrossRef][PubMed]
11. Thakore, K.N.; Mehendale, H.M. Role of hepatocellular regeneration in CCl4 autoprotection. Toxicol. Path
1991, 19, 47–58. [CrossRef][PubMed]
12. Rudraiah, S.; Rohrer, P.R.; Gurevich, I.; Goedken, M.J.; Rasmussen, T.; Hines, R.N.; Manautou, J.E. Tolerance
to acetaminophen hepatotoxicity in the mouse model of autoprotection is associated with induction of
flavin-containing monooxygenase-3 (FMO3) in hepatocytes. Toxicol. Sci. 2014, 27, kfu124. [CrossRef]
[PubMed]
13. Hodgkin, A.L.; Huxley, A.F. A quantitative description of membrane current and its application to conduction
and excitation in nerve. J. Physiol. 1952, 117, 500–544. [CrossRef][PubMed]
14. Russmann, S.; Kullak-Ublick, G.A.; Grattagliano, I. Current concepts of mechanisms in drug-induced
hepatotoxicity. Curr. Med. Chem. 2009, 16, 3041–3053. [CrossRef][PubMed]
15. Bassler, N.; Loeffler, C.; Mangin, P.; Yuan, Y.; Schwarz, M.; Hagemeyer, C.E.; Eisenhardt, S.U.; Ahrens, I.;
Bode, C.; Jackson, S.P.; et al. A mechanistic model for paradoxical platelet activation by ligand-mimetic
αIIbβ3 (GPIIb/IIIa) antagonists. Arterioscl. Thromb. Vasc. Biol. 2007, 27, E9–E15. [CrossRef][PubMed]
16. Zajac, F.E. Muscle and tendon Properties models scaling and application to biomechanics and motor. Crit. Rev.
Biomed. Eng. 1989, 17, 359–411. [PubMed]
17. Li, L.; Gardner, I.; Rose, R.; Jamei, M. Incorporating target shedding into a minimal PBPK–TMDD model for
monoclonal antibodies. CPT Pharmacomet. Syst. Pharmacol. 2014, 3, e96. [CrossRef][PubMed]
18. Ayllón, D.; Railsback, S.F.; Vincenzi, S.; Groeneveld, J.; Almodóvar, A.; Grimm, V. InSTREAM-Gen: Modelling
eco-evolutionary dynamics of trout populations under anthropogenic environmental change. Ecol. Mod.
2016, 326, 36–53. [CrossRef]
19. Norton, K.A.; Wininger, M.; Bhanot, G.; Ganesan, S.; Barnard, N.; Shinbrot, T. A 2D mechanistic model
of breast ductal carcinoma in situ (DCIS) morphology and progression. J. Theor. Biol. 2010, 263, 393–406.
[CrossRef][PubMed]
20. Clegg, L.E.; Mac Gabhann, F. Molecular mechanism matters: Benefits of mechanistic computational models
for drug development. Pharmacol. Res. 2015, 99, 149–154. [CrossRef][PubMed]
21. Bangs, A.; Bowling, K.; Paterson, T. Simulating Patient-Specific Outcomes. US Patent 10/961,523, 7 October 2004.
22. Lytton, W.W.; Sejnowski, T.J. Simulations of cortical pyramidal neurons synchronized by inhibitory
interneurons. J. Neurophysiol. 1991, 66, 1059–1079. [CrossRef][PubMed]
23. Wang, X.J.; Buzsáki, G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network
model. J. Neurosci. 1996, 16, 6402–6413. [CrossRef][PubMed]
24. Neymotin, S.A.; Lazarewicz, M.T.; Sherif, M.; Contreras, D.; Finkel, L.H.; Lytton, W.W. Ketamine disrupts
theta modulation of gamma in a computer model of hippocampus. J. Neurosci. 2011, 31, 11733–11743.
[CrossRef][PubMed]
25. Xue, C.; Shtylla, B.; Brown, A. A stochastic multiscale model that explains the segregation of axonal
microtubules and neurofilaments in neurological diseases. PLoS Comput. Biol. 2015, 11, e1004406. [CrossRef]
[PubMed]
201
4.
Bechtel, W.; Abrahamsen, A. Explanation: A mechanist alternative. Stud. Hist. Philos. Sci. Part C 2005, 36,
421–441. [CrossRef]
5.
Craver, C.F. Explaining the Brain: Mechanisms and the Mosaic Unity of Neuroscience; Oxford University Press:
Oxford, UK, 2007.
6.
Illari, P.M.; Williamson, J. What is a mechanism? Thinking about mechanisms across the sciences. European.
J. Philos. Sci. 2012, 2, 119–135. [CrossRef]
7.
Merriam-Webster Unabridged. Available online: http://unabridged.merriam-webster.com/ (accessed on
2 October 2016).
8.
Craver, C.F. When mechanistic models explain. Synthese 2006, 153, 355–376. [CrossRef]
9.
Darden, L. Thinking again about biological mechanisms. Philos. Sci. 2009, 75, 958–969. [CrossRef]
10. Miyakawa, K.; Albee, R.; Letzig, L.G.; Lehner, A.F.; Scott, M.A.; Buchweitz, J.P.; James, L.P.; Ganey, P.E.;
Roth, R.A. A Cytochrome P450–independent mechanism of acetaminophen-induced injury in cultured
mouse hepatocytes. J. Pharmacol. Exp. Therap. 2015, 354, 230–237. [CrossRef][PubMed]
11. Thakore, K.N.; Mehendale, H.M. Role of hepatocellular regeneration in CCl4 autoprotection. Toxicol. Path
1991, 19, 47–58. [CrossRef][PubMed]
12. Rudraiah, S.; Rohrer, P.R.; Gurevich, I.; Goedken, M.J.; Rasmussen, T.; Hines, R.N.; Manautou, J.E. Tolerance
to acetaminophen hepatotoxicity in the mouse model of autoprotection is associated with induction of
flavin-containing monooxygenase-3 (FMO3) in hepatocytes. Toxicol. Sci. 2014, 27, kfu124. [CrossRef]
[PubMed]
13. Hodgkin, A.L.; Huxley, A.F. A quantitative description of membrane current and its application to conduction
and excitation in nerve. J. Physiol. 1952, 117, 500–544. [CrossRef][PubMed]
14. Russmann, S.; Kullak-Ublick, G.A.; Grattagliano, I. Current concepts of mechanisms in drug-induced
hepatotoxicity. Curr. Med. Chem. 2009, 16, 3041–3053. [CrossRef][PubMed]
15. Bassler, N.; Loeffler, C.; Mangin, P.; Yuan, Y.; Schwarz, M.; Hagemeyer, C.E.; Eisenhardt, S.U.; Ahrens, I.;
Bode, C.; Jackson, S.P.; et al. A mechanistic model for paradoxical platelet activation by ligand-mimetic
αIIbβ3 (GPIIb/IIIa) antagonists. Arterioscl. Thromb. Vasc. Biol. 2007, 27, E9–E15. [CrossRef][PubMed]
16. Zajac, F.E. Muscle and tendon Properties models scaling and application to biomechanics and motor. Crit. Rev.
Biomed. Eng. 1989, 17, 359–411. [PubMed]
17. Li, L.; Gardner, I.; Rose, R.; Jamei, M. Incorporating target shedding into a minimal PBPK–TMDD model for
monoclonal antibodies. CPT Pharmacomet. Syst. Pharmacol. 2014, 3, e96. [CrossRef][PubMed]
18. Ayllón, D.; Railsback, S.F.; Vincenzi, S.; Groeneveld, J.; Almodóvar, A.; Grimm, V. InSTREAM-Gen: Modelling
eco-evolutionary dynamics of trout populations under anthropogenic environmental change. Ecol. Mod.
2016, 326, 36–53. [CrossRef]
19. Norton, K.A.; Wininger, M.; Bhanot, G.; Ganesan, S.; Barnard, N.; Shinbrot, T. A 2D mechanistic model
of breast ductal carcinoma in situ (DCIS) morphology and progression. J. Theor. Biol. 2010, 263, 393–406.
[CrossRef][PubMed]
20. Clegg, L.E.; Mac Gabhann, F. Molecular mechanism matters: Benefits of mechanistic computational models
for drug development. Pharmacol. Res. 2015, 99, 149–154. [CrossRef][PubMed]
21. Bangs, A.; Bowling, K.; Paterson, T. Simulating Patient-Specific Outcomes. US Patent 10/961,523, 7 October 2004.
22. Lytton, W.W.; Sejnowski, T.J. Simulations of cortical pyramidal neurons synchronized by inhibitory
interneurons. J. Neurophysiol. 1991, 66, 1059–1079. [CrossRef][PubMed]
23. Wang, X.J.; Buzsáki, G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network
model. J. Neurosci. 1996, 16, 6402–6413. [CrossRef][PubMed]
24. Neymotin, S.A.; Lazarewicz, M.T.; Sherif, M.; Contreras, D.; Finkel, L.H.; Lytton, W.W. Ketamine disrupts
theta modulation of gamma in a computer model of hippocampus. J. Neurosci. 2011, 31, 11733–11743.
[CrossRef][PubMed]
25. Xue, C.; Shtylla, B.; Brown, A. A stochastic multiscale model that explains the segregation of axonal
microtubules and neurofilaments in neurological diseases. PLoS Comput. Biol. 2015, 11, e1004406. [CrossRef]
[PubMed]
201