@article {24905,
	title = {A Biophysical Systems Approach to Identifying the Pathways of Acute and Chronic Doxorubicin Mitochondrial Cardiotoxicity},
	journal = {PLoS Computational Biology},
	volume = {12},
	year = {2016},
	publisher = {PLOS},
	abstract = {The clinical use of the anthracycline doxorubicin is limited by its cardiotoxicity which is associated with mitochondrial dysfunction. Redox cycling, mitochondrial DNA damage and electron transport chain inhibition have been identified as potential mechanisms of toxicity. However, the relative roles of each of these proposed mechanisms are still not fully understood. The purpose of this study is to identify which of these pathways independently or in combination are responsible for doxorubicin toxicity. A state of the art mathematical model of the mitochondria including the citric acid cycle, electron transport chain and ROS production and scavenging systems was extended by incorporating a novel representation for mitochondrial DNA damage and repair. In silico experiments were performed to quantify the contributions of each of the toxicity mechanisms to mitochondrial dysfunction during the acute and chronic stages of toxicity. Simulations predict that redox cycling has a minor role in doxorubicin cardiotoxicity. Electron transport chain inhibition is the main pathway for acute toxicity for supratherapeutic doses, being lethal at mitochondrial concentrations higher than 200μM. Direct mitochondrial DNA damage is the principal pathway of chronic cardiotoxicity for therapeutic doses, leading to a progressive and irreversible long term mitochondrial dysfunction.},
	doi = {     http://dx.doi.org/10.1371/journal.pcbi.1005214},
	author = {Bernardo Lino {de Oliveira} and Steven A {Niederer}}
}
@inproceedings {25258,
	title = {Computational models of doxorubicin mitochondria cardiotoxicity},
	journal = {Journal of Pharmacological and Toxicological Methods},
	volume = {81},
	year = {2016},
	publisher = {Elsevier},
	author = {Bernardo Lino {de Oliveira} and Steven A {Niederer}},
	editor = {Pugsley, Michael}
}
@article {Land:2015dq,
	title = {Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour},
	journal = {Proceedings of the Royal Society A},
	volume = {471},
	year = {2015},
	month = {12/2015},
	publisher = {The Royal Society},
	abstract = {Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5\%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.},
	author = {Land, Sander and Arens, Sander and Christoph M {Augustin} and Baron, Lukas and Castro, Sebastian and Crozier, Andrew and Favino, Marco and Thomas E {Fastl} and Fritz, Thomas and Gao, Hao and Gizzi, Alessio and Boyce E {Griffith} and Daniel E {Hurtado} and Krause, Rolf and Luo, Xiaoyu and Martyn P {Nash} and Pezzuto, Simone and Plank, Gernot and Rossi, Simone and Ruprecht, Daniel and Seemann, Gunnar and Nicolas P. {Smith} and Sundnes, Joakim and Rice, Jeremy and Natalia A. {Trayanova} and Wang, Dafang and Zhinuo Jenny {Wang} and Steven A {Niederer}}
}
@article {23371,
	title = {A computational pipeline for quantification of mouse myocardial stiffness parameters},
	journal = {Computers in Biology and Medicine},
	volume = {53},
	year = {2014},
	pages = {65{\textendash}75},
	publisher = {Comput. Biol. Med.},
	abstract = {The mouse is an important model for theoretical-experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties. A mouse heart was excised and the left ventricle experimentally inflated from 0 to 1.44kPa in eleven steps, and the resulting deformation was estimated by echocardiography and speckle tracking. An in silico counterpart to this experiment was built using finite element methods and data on ventricular tissue microstructure from diffusion tensor {MRI}. This model assumed a hyperelastic, transversely isotropic material law to describe the force-deformation relationship, and was simulated for many parameter scenarios, covering the relevant range of parameter space. To identify well-fitting parameter scenarios, we compared experimental and simulated outcomes across the whole range of pressures, based partly on gross phenotypes (volume, elastic energy, and short- and long-axis diameter), and partly on node positions in the geometrical mesh. This identified a narrow region of experimentally compatible values of the material parameters. Estimation turned out to be more precise when based on changes in gross phenotypes, compared to the prevailing practice of using displacements of the material points. We conclude that the presented experimental setup and computational pipeline is a viable method that deserves wider application.},
	issn = {1879-0534},
	doi = {10.1016/j.compbiomed.2014.07.013},
	author = {Nordb{\o}, Oyvind and Lamata, Pablo and Land, Sander and Steven A {Niederer} and Jan M. {Aronsen} and William E. {Louch} and Sjaastad, Ivar and Martens, Harald and Arne B. {Gjuvsland} and T{\o}ndel, Kristin and Torp, Hans and Lohezic, Maelene and Jurgen E. {Schneider} and Espen W. {Remme} and Nicolas P. {Smith} and Stig W. {Omholt}}
}
@article {23375,
	title = {Insight into Model Mechanisms through Automatic Parameter Fitting: A new Methodological Framework for Model Development},
	journal = {{BMC} Systems Biology},
	volume = {8},
	year = {2014},
	pages = {59},
	publisher = {BioMedCentral},
	author = {T{\o}ndel, Kristin and Steven A {Niederer} and Land, Sander and Nicolas P. {Smith}}
}
@article {23372,
	title = {Quantifying inter-species differences in contractile function through biophysical modelling},
	journal = {Journal of Physiology},
	volume = {593},
	year = {2014},
	pages = {1083-1111},
	publisher = {Wiley},
	doi = {10.1113/jphysiol.2014.279232},
	author = {T{\o}ndel, Kristin and Steven A {Niederer} and Land, Sander and Nicolas P. {Smith}}
}
@article {Simula.simula.2680,
	title = {Genotype-Phenotype Map Characteristics of an in Silico Heart Cell},
	journal = {Frontiers in Physiology},
	volume = {2},
	number = {1},
	year = {2011},
	pages = {106},
	publisher = {NCBI},
	author = {Jon Olav {Vik} and Arne B. {Gjuvsland} and Li, Liren and T{\o}ndel, Kristin and Steven A {Niederer} and Nicolas P. {Smith} and Peter J. {Hunter} and Stig W. {Omholt}}
}
@article {Simula.simula.230,
	title = {N-Version Benchmark Evaluation of Cardiac Tissue Electrophysiology Simulators},
	journal = {Philosophical Transactions of the Royal Society A},
	volume = {369},
	number = {1954},
	year = {2011},
	month = {November},
	pages = {4331-51},
	abstract = {Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.},
	doi = {10.1098/rsta.2011.0139},
	author = {Steven A {Niederer} and Kerfoot, Eric and Benson, Alana and Bernabeu, Miguel and Bernus, Olivier and Cherry, Elizabeth and Clayton, Richard and Fenton, Flavio and Garny, Alan and Heidenreich, Elvio and Land, Sander and Maleckar, Molly and Pathmanathan, Pras and Plank, Gernot and Rodriguez, Jose and Roy, Ishani and Sachse, Frank and Seemann, Gunnar and Skavhaug, Ola and Nicolas P. {Smith}}
}
