@article {43400,
	title = {Multiscale computational modeling of the effects of 2{\textquoteright}-deoxy-ATP on cardiac muscle calcium handling},
	journal = {Journal of Applied Physics},
	volume = {134},
	year = {2023},
	month = {08/2023},
	publisher = {AIP Publishing},
	abstract = {2{\textquoteright}-Deoxy-ATP (dATP), a naturally occurring near analog of ATP, is a well-documented myosin activator that has been shown to increase contractile force, improve pump function, and enhance lusitropy in the heart. Calcium transients in cardiomyocytes with elevated levels of dATP show faster calcium decay compared with cardiomyocytes with basal levels of dATP, but the mechanisms behind this are unknown. Here, we design and utilize a multiscale computational modeling framework to test the hypothesis that dATP acts on the sarcoendoplasmic reticulum calcium-ATPase (SERCA) pump to accelerate calcium re-uptake into the sarcoplasmic reticulum during cardiac relaxation. Gaussian accelerated molecular dynamics simulations of human cardiac SERCA2A in the E1\&nbsp;apo, ATP-bound and dATP-bound states showed that dATP forms more stable contacts in the nucleotide binding pocket of SERCA and leads to increased closure of cytosolic domains. These structural changes ultimately lead to changes in calcium binding, which we assessed using Brownian dynamics simulations. We found that dATP increases calcium association rate constants to SERCA and that dATP binds to\&nbsp;apo\&nbsp;SERCA more rapidly than ATP. Using a compartmental ordinary differential equation model of human cardiomyocyte excitation-contraction coupling, we found that these increased association rate constants contributed to the accelerated rates of calcium transient decay observed experimentally. This study provides clear mechanistic evidence of enhancements in cardiac SERCA2A pump function due to interactions with dATP.},
	doi = {https://doi.org/10.1063/5.0157935},
	author = {Marcus T. {Hock} and Teitgen, Abigail and Kimberly J {McCabe} and Sophia P. {Hirakis} and Huber, Gary and Regnier, Michael and Rommie E. {Amaro} and Andrew J. {McCammon} and Andrew D. {McCulloch}}
}
@misc {43093,
	title = {Development of a Biventricular Coordinate System with Representation of an Anatomically Detailed Base},
	howpublished = {Tampere },
	year = {2022},
	type = {Conference},
	author = {Pankewitz, Lisa and Govil, Sachin and Kristian Gregorius {Hustad} and James C {Perry} and Hedge, Sanjeet and Tang, Renxiang and Andrew D. {McCulloch} and Arevalo, Hermenegild}
}
@inbook {28434,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries},
	booktitle = {Zipes and Jalife{\textquoteright}s Cardiac Electrophysiology: From Cell to Bedside},
	volume = {1},
	year = {2021},
	month = {12/2021},
	pages = {362-375},
	publisher = { Elsevier},
	organization = { Elsevier},
	edition = {8},
	chapter = {32},
	author = {Andrew G {Edwards} and van den Brink, Jonas and Andrew D. {McCulloch}},
	editor = {Jalife, Jose and William G {Stevenson}}
}
@article {27048,
	title = {A computational study on integrated mechanisms of mechano-electric feedback in ischemic arrhythmogenesis},
	journal = {SAGE},
	year = {2020},
	publisher = {Clinical Medicine Insights: Cardiology},
	author = {Timmermann, Viviane and Alexander T. {Quinn} and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {timmermann2020mechano,
	title = {Mechano-electric coupling and arrhythmogenic current generation in a computational model of coupled myocytes},
	journal = {Frontiers in physiology},
	volume = {11},
	year = {2020},
	pages = {1573},
	publisher = {Frontiers},
	author = {Timmermann, Viviane and Andrew D. {McCulloch}}
}
@misc {27607,
	title = {Multiscale modelling determines mechanisms of action for 2{\textquoteright}-deoxy-ATP, a myosin activating therapeutic for heart failure},
	howpublished = {VPH 2020, Paris, France (Virtual)},
	year = {2020},
	publisher = {VPH 2020},
	author = {Kimberly J {McCabe} and Aboelkassem, Yasser and Teitgen, Abigail and Regnier, Michael and Andrew D. {McCulloch}}
}
@article {27460,
	title = {Predicting the effects of dATP on cardiac contraction using multiscale modeling of the sarcomere},
	journal = {Archives of Biochemistry and Biophysics},
	volume = {695},
	year = {2020},
	month = {11/2020},
	pages = {108582},
	publisher = {Elsevier},
	abstract = {2{\textquoteright}-deoxy-ATP (dATP) is a naturally occurring small molecule that has shown promise as a therapeutic because it significantly increases cardiac myocyte force development even at low dATP/ATP ratios. To investigate mechanisms by which dATP alters myosin crossbridge dynamics, we used Brownian dynamics simulations to calculate association rates between actin and ADP- or dADP-bound myosin. These rates were then directly incorporated in a mechanistic Monte Carlo Markov Chain model of cooperative sarcomere contraction. A unique combination of increased powerstroke and detachment rates was required to match experimental steady-state and kinetic data for dATP force production in rat cardiac myocytes when the myosin attachment rate in the model was constrained by the results of a Brownian dynamics simulation. Nearest-neighbor cooperativity was seen to contribute to, but not fully explain, the steep relationship between dATP/ATP ratio and steady-state force-development observed at lower dATP concentrations. Dynamic twitch simulations performed using measured calcium transients as inputs showed that the effects of dATP on the crossbridge alone were not sufficient to explain experimentally observed enhancement of relaxation kinetics by dATP treatment. Hence, dATP may also affect calcium handling even at low concentrations. By enabling the effects of dATP on sarcomere mechanics to be predicted, this multi-scale modelling framework may elucidate the molecular mechanisms by which dATP can have therapeutic effects on cardiac contractile dysfunction.},
	doi = {10.1016/j.abb.2020.108582},
	author = {Kimberly J {McCabe} and Aboelkassem, Yasser and Teitgen, Abigail and Huber, Gary and Andrew J. {McCammon} and Regnier, Michael and Andrew D. {McCulloch}}
}
@article {timmermann2019arrhythmogenic,
	title = {Arrhythmogenic current generation by myofilament-triggered Ca2+ release and sarcomere heterogeneity},
	journal = {Biophysical Journal},
	volume = {117},
	year = {2019},
	pages = {2471-2485},
	publisher = {Cell Press},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Wall, Samuel and Sundnes, Joakim and Andrew D. {McCulloch}}
}
@misc {26335,
	title = {Autonomic Modelling of Interaction between Coronary Perfusion Flow and Myocardium Mechanics using Computational Poroelasticity},
	howpublished = {International Society of Autonomic Neuroscience, Los Angeles, CA, USA},
	year = {2019},
	publisher = {International Society of Autonomic Neuroscience, 2019.},
	abstract = {Autonomic control and modelling the cross-talk between blood flow in coronary vessels and ventricular wall mechanical deformations are central problems in mechanocardiac physiology. In this study, we use a multi-scale approach that includes multi-physics modules of the heart with autonomic control, to accurately model this complex interaction between coronary perfusion and myocardium mechanics. In particular, we implement a 3D finite element numerical scheme to account for this coupling using a reconstructed and geometrically-accurate anatomical model of a porcine subject, Figure 1(A). A mathematical model using statistical measurements and space filling topology is used to specify the coronary tree networks in the finite element computational model, Figure 1(B). A multi-compartment poroelastic governing equations of the blood-soft tissue interactions are derived. The evolution equations for both blood and soft tissue phases are described in the Lagrangian frame of reference. The complex network of blood vessel that surround the myocardium tissue are integrated using a reduced order modelling of Darcy law with a heterogeneous permeability tensor along with the finite deformation elasticity of the myocardium. The derived methodology approach is tested on simplified 2D and 3D myocardium poroelastic geometries with customized modules and well-posed prescribed traction boundary conditions at a finite set of coronary compartments, Figure 1(C-D). Results are given for\&nbsp;the perfusion of the left ventricle deformation under passive inflation that show in particular wall compliance remodelling associated with perfusion dysfunction.},
	author = {Aboelkassem, Yasser and Alexandra K. {Diem} and Valen-Sendstad, Kristian and Andrew D. {McCulloch}}
}
@article {26563,
	title = {Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin},
	journal = {Proceedings of the National Academy of Sciences},
	year = {2019},
	month = {05/2019},
	publisher = {PNAS},
	abstract = {The naturally occurring nucleotide 2-deoxy-adenosine 5'-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer and millisecond time scales, demonstrating the ability to make both structural measurements and quantitative kinetic estimates of weak actin{\textendash}myosin interactions that underpin sarcomere dynamics. Exploiting dATP as a molecular probe, we assess how small changes in myosin structure translate to electrostatic-based changes in sarcomere function to augment contractility in cardiac muscle. Through Brownian dynamics simulation and computational structural analysis, we found that deoxy-hydrolysis products [2-deoxy-adenosine 5'-diphosphate (dADP) and inorganic phosphate (Pi)] bound to prepowerstroke myosin induce an allosteric restructuring of the actin-binding surface on myosin to increase the rate of cross-bridge formation. We then show experimentally that this predicted effect translates into increased electrostatic interactions between actin and cardiac myosin in vitro. Finally, using small-angle X-ray diffraction analysis of sarcomere structure, we demonstrate that the proposed increased electrostatic affinity of myosin for actin causes a disruption of the resting conformation of myosin motors, resulting in their repositioning toward the thin filament before activation. The dATP-mediated structural alterations in myosin reported here may provide insight into an improved criterion for the design or selection of small molecules to be developed as therapeutic agents to treat systolic dysfunction.},
	issn = {0027-8424},
	doi = {10.1073/pnas.1905028116},
	url = {http://www.pnas.org/lookup/doi/10.1073/pnas.1905028116https://syndication.highwire.org/content/doi/10.1073/pnas.1905028116},
	author = {Joseph D {Powers} and Yuan, Chen-Ching and Kimberly J {McCabe} and Jason D {Murray} and Matthew Carter {Childers} and Galina V {Flint} and Moussavi-Harami, Farid and Mohran, Saffie and Castillo, Romi and Zuzek, Carla and Ma, Weikang and Daggett, Valerie and Andrew D. {McCulloch} and Thomas C {Irving} and Regnier, Michael}
}
@misc {27047,
	title = {Mechano-Electric Coupling and Arrhythmogenic Current Generation in a Computational Model of Coupled Myocytes},
	howpublished = {Cardiac Physiome, Maastricht, Netherlands},
	year = {2019},
	publisher = {Cardiac Physiome},
	author = {Timmermann, Viviane and Alexander T. {Quinn} and Andrew D. {McCulloch}}
}
@inproceedings {27043,
	title = {Mechano-electric feedback and arrhythmogenic current generation in a computational model of coupled myocytes},
	journal = {ICBME2019--YC Fung 100th Birthday Conference},
	year = {2019},
	publisher = {Tech Science Press},
	author = {Timmermann, Viviane and Vincent, Kevin and Sundnes, Joakim and Andrew D. {McCulloch}}
}
@article {26787,
	title = {Multiscale Models of Cardiac Muscle Biophysics and Tissue Remodeling in Hypertrophic Cardiomyopathies},
	journal = {Current Opinion in Biomedical Engineering},
	volume = {11},
	year = {2019},
	pages = {35-44},
	publisher = {Elsevier},
	doi = {https://doi.org/10.1016/j.cobme.2019.09.005},
	author = {Aboelkassem, Yasser and Joseph D {Powers} and Kimberly J {McCabe} and Andrew D. {McCulloch}}
}
@misc {27046,
	title = {A one-dimensional computational study of mechano-electric feedback and arrhythmogenic current generation},
	howpublished = {Gordon Research Conference "Cardiac Arrhythmia Mechanisms", Barga, Italy},
	year = {2019},
	author = {Timmermann, Viviane and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {26640,
	title = {Properties of cardiac conduction in a cell-based computational model},
	journal = {PLoS Computational Biology},
	volume = {15},
	number = {e1007042},
	year = {2019},
	month = {05/2019},
	publisher = {Public Library of Science},
	abstract = {The conduction of electrical signals through cardiac tissue is essential for maintaining the function of the heart, and conduction abnormalities are known to potentially lead to life-threatening arrhythmias. The properties of cardiac conduction have therefore been the topic of intense study for decades, but a number of questions related to the mechanisms of conduction still remain unresolved. In this paper, we demonstrate how the so-called EMI model may be used to study some of these open questions. In the EMI model, the extracellular space, the cell membrane, the intracellular space and the cell connections are all represented as separate parts of the computational domain, and the model therefore allows for study of local properties that are hard to represent in the classical homogenized bidomain or monodomain models commonly used to study cardiac conduction. We conclude that a non-uniform sodium channel distribution increases the conduction velocity and decreases the time delays over gap junctions of reduced coupling in the EMI model simulations. We also present a theoretical optimal cell length with respect to conduction velocity and consider the possibility of ephaptic coupling (i.e. cell-to-cell coupling through the extracellular potential) acting as an alternative or supporting mechanism to gap junction coupling. We conclude that for a non-uniform distribution of sodium channels and a sufficiently small intercellular distance, ephaptic coupling can influence the dynamics of the sodium channels and potentially provide cell-to-cell coupling when the gap junction connection is absent.},
	doi = {10.1371/journal.pcbi.1007042},
	url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007042},
	author = {Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Andrew D. {McCulloch} and Tveito, Aslak}
}
@article {27946,
	title = {Scar shape analysis and simulated electrical instabilities in a non-ischemic dilated cardiomyopathy patient cohort},
	journal = {PLOS Computational Biology},
	year = {2019},
	month = {Apr-10-2021},
	publisher = {PLOS},
	url = {https://dx.plos.org/10.1371/journal.pcbi.100742},
	author = {Balaban, Gabriel and Brian P. {Halliday} and Bai, Wenjia and Porter, Bradley and Malvuccio, Carlotta and Lamata, Pablo and Christopher A. {Rinaldi} and Plank, Gernot and Rueckert, Daniel and Sanjay K. {Prasad} and Martin J. {Bishop}},
	editor = {Andrew D. {McCulloch}}
}
@article {26786,
	title = {A Stochastic Multiscale Model of Cardiac Thin Filament Activation Using Brownian-Langevin Dynamics},
	journal = {Biophysical Journal},
	volume = {117},
	year = {2019},
	pages = {2255-2272},
	publisher = {Cell Press},
	abstract = {We use Brownian-Langevin dynamics principles to derive a coarse-graining multiscale myofilament model that can describe the thin-filament activation process during contraction. The model links atomistic molecular simulations of protein-protein interactions in the thin-filament regulatory unit to sarcomere-level activation dynamics. We first calculate the molecular interaction energy between tropomyosin and actin surface using Brownian dynamics simulations. This energy profile is then generalized to account for the observed tropomyosin transitions between its regulatory stable states. The generalized energy landscape then served as a basis for developing a filament-scale model using Langevin dynamics. This integrated analysis, spanning molecular to thin-filament scales, is capable of tracking the events of the tropomyosin conformational changes as it moves over the actin surface. The tropomyosin coil with flexible overlap regions between adjacent tropomyosins is represented in the model as a system of coupled stochastic ordinary differential equations. The proposed multiscale approach provides a more detailed molecular connection between tropomyosin dynamics, the trompomyosin-actin interaction-energy landscape, and the generated force by the sarcomere.},
	doi = {10.1016/j.bpj.2019.08.003},
	author = {Aboelkassem, Yasser and Kimberly J {McCabe} and Huber, Gary and Regnier, Michael and Andrew J. {McCammon} and Andrew D. {McCulloch}}
}
@misc {27045,
	title = {A computational study of the contribution of mechano-electric feedback to arrhythmogenic current generation},
	howpublished = {Berlin, Germany},
	year = {2018},
	publisher = {Heart by Numbers, Biophysical Society},
	author = {Timmermann, Viviane and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@misc {26463,
	title = {A Markov State Model of the Sarcomere to Explain the  Effects of dATP on Cardiac Contraction},
	year = {2018},
	address = {Biophysical Society 62nd Annual Meeting, San Francisco CA},
	abstract = {2-deoxy-ATP is a naturally occurring homolog of ATP known to increase force production, enhance crossbridge cycling speed, and accelerate the removal of Ca2+ from the cytoplasm during cardiac muscle cell relaxation. At low ratios of dATP to ATP in cardiomyocytes, steady state force has been shown to increase nonlinearly at physiological [Ca2+]1. The purpose of this study is to discover specific mechanisms by which dATP alters myosin dynamics within the sarcomere using multiscale computational modeling. We have developed a comprehensive mechanistic Monte Carlo Markov State model of rat sarcomere contraction which includes cooperativity in both thin filament activation and crossbridge cycling through nearest-neighbor Tropomyosin (Tm) interactions as well as cross bridge attachment effect on neighboring myosin on the thick filament. This novel sarcomere model was used to test the effects of dATP on contractility within the sarcomere.\&nbsp; We combined experimental data on the subcellular, cellular, and organ level as well as Molecular Dynamics (MD) data to parameterize and validate the model. We tested combinations of 4 possible kinetic transitions in which dATP is hypothesized to affect crossbridge cycling and tested various degrees of cooperativity in the system to find a likely combination of mechanisms by which dATP affects contraction.},
	author = {Kimberly J {McCabe} and Aboelkassem, Yasser and Dewan, Sukriti and Regnier, Michael and Andrew D. {McCulloch}}
}
@misc {aboelkassem2018turning,
	title = {Turning the Azimuthal Motions of Adjacent Tropomyosins into a Coupled N-body Problem in a Brownian Model of Cardiac Thin Filament Activation},
	howpublished = {Biophysical Journal},
	year = {2018},
	publisher = {Elsevier},
	address = {San Francisco, California/U.S.A.},
	author = {Aboelkassem, Yasser and Kimberly J {McCabe} and Huber, Gary and Sundnes, Joakim and Andrew D. {McCulloch}}
}
@article {26458,
	title = {Insights and Challenges of Multi-Scale Modeling of Sarcomere Mechanics in cTn and Tm DCM Mutants{\textemdash}Genotype to Cellular Phenotype},
	journal = {Frontiers in Physiology},
	volume = {14},
	number = {151},
	year = {2017},
	month = {03/2017},
	publisher = {Frontiers in Physiology},
	doi = {10.3389/fphys.2017.00151},
	url = {http://journal.frontiersin.org/article/10.3389/fphys.2017.00151/fullhttp://journal.frontiersin.org/article/10.3389/fphys.2017.00151/full},
	author = {Dewan, Sukriti and Kimberly J {McCabe} and Regnier, Michael and Andrew D. {McCulloch}}
}
@misc {25790,
	title = {Integrated Mechanisms of Mechano-Electric feedback in Ischemic Arrhythmogenesis},
	howpublished = {Bergen, Norway},
	year = {2017},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel and T. A. {Quinn}}
}
@article {25788,
	title = {An integrative appraisal of mechano-electric feedback mechanisms in the heart},
	journal = {Progress in biophysics and molecular biology},
	volume = {130},
	year = {2017},
	pages = {404{\textendash}417},
	publisher = {Elsevier},
	author = {Timmermann, Viviane and Lars A {Dejgaard} and Kristina H {Haugaa} and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel}
}
@misc {25789,
	title = {Role of Electromechanical Feedback in Stretch Induced Arrhythmias : From Single Myocyte to Multicellular Level},
	year = {2017},
	month = {02/2017},
	address = {Gordon Research Conference on Arrhythmia Mechanisms, Ventura, California, USA},
	author = {Timmermann, Viviane and Lars A {Dejgaard} and Andrew D. {McCulloch} and Kristina H {Haugaa} and Andrew G {Edwards} and Wall, Samuel}
}
@article {23677,
	title = {Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {96},
	year = {2016},
	pages = {63-71},
	publisher = {Academic Press},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@inbook {Simula.simula.2290,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (7th Edition)},
	booktitle = {Cardiac Electrophysiology: From Cell to Bedside},
	year = {2016},
	publisher = {Elsevier Science},
	organization = {Elsevier Science},
	edition = {7},
	chapter = {33},
	isbn = {9781455728565},
	author = {Andrew G {Edwards} and Johan Elon {Hake} and Anushka P. {Michailova} and Hoshijima, Masahiko and Andrew D. {McCulloch}},
	editor = {Zipes, Douglas and Jalife, Jose}
}
@article {24492,
	title = {Combination of Neural Inverse Optimal Control with a Kernel-Based Regularization Learning Algorithm to Prevent Hypoglycemia in Type 1 Diabetes Patients},
	journal = {IEEE Transactions on Neural Networks and Learning Systems},
	year = {2016},
	publisher = {IEEE},
	abstract = {Hypoglycemia periods in Type 1 Diabetes mellitus (T1DM) patients are a dangerous condition leading to serious acute complications, such as diabetic coma or death.Despite recent technological and scientific advances in T1DM therapy management, prevention of severe hypoglycemic periods still remains a challenge.\&nbsp;In this paper, we present a novel combination of a neural inverse optimal control via control Lyapunov function (CLF) combined with a kernel-based regularization learningpredictive algorithm (KAR) for optimal control of the blood glucose levels with a strong focus on timely detection and prevention of acute debilitating and harmful hypoglycemicevents. We describe how the proposed scheme can be used for aforementioned problem and report the results of the testson University of Virginia (UVA)/Padova Simulator as well as comparing them with existing literature. The performance assessment of the algorithms has been made with the use of control variability grid analysis (CVGA).},
	author = {Leon, Blanca and Naumova, Valeriya and Ruiz-Velazquez, Eduardo and Andrew D. {McCulloch} and Sanchez, Edgar}
}
@article {24996,
	title = {Computing rates of Markov models of voltage-gated ion channels by inverting partial differential equations governing the probability density functions of the conducting and non-conducting states},
	journal = {Mathematical Biosciences},
	volume = {277},
	year = {2016},
	pages = {126-135},
	publisher = {Elsevier Inc},
	author = {Tveito, Aslak and Glenn T. {Lines} and Andrew G {Edwards} and Andrew D. {McCulloch}}
}
@article {26459,
	title = {Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation{\textemdash}An Integrated Multiscale Modeling Study},
	journal = {The Journal of Physical Chemistry B},
	volume = {120},
	year = {2016},
	month = {08/2016},
	pages = {8264 - 8275},
	publisher = {The Journal of Physical Chemistry B},
	issn = {1520-6106},
	doi = {10.1021/acs.jpcb.6b01950},
	url = {http://pubs.acs.org/doi/10.1021/acs.jpcb.6b01950http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.6b01950},
	author = {Dewan, Sukriti and Kimberly J {McCabe} and Regnier, Michael and Andrew D. {McCulloch} and Lindert, Steffen}
}
@misc {25791,
	title = {Role of Electromechanical Feedback in Mitral Valve Prolapse Arrhythmia},
	year = {2016},
	month = {09/2016},
	publisher = {Conference on Cardiac Mechano-Electric Couping and Arrhythmias},
	address = {Freiburg, Germany},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel}
}
@article {23810,
	title = {Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {In Press},
	year = {2015},
	publisher = {Academic Press},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@article {23999,
	title = {High-order finite element methods for cardiac monodomain simulations},
	journal = {Frontiers in Physiology},
	year = {2015},
	month = {08/2015},
	publisher = {Frontiers Media S.A.},
	abstract = {Computational modeling of tissue-scale cardiac electrophysiology requires numerically converged solutions to avoid spurious artifacts. The steep gradients inherent to cardiac action potential propagation necessitate fine spatial scales and therefore a substantial computational burden. The use of high-order interpolation methods has previously been proposed for these simulations due to their theoretical convergence advantage. In this study, we compare the convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed cubic Hermite-style serendipity interpolation methods for finite element simulations of the cardiac monodomain equation. The high-order methods reach converged solutions with fewer degrees of freedom and longer element edge lengths than traditional linear elements. Additionally, we propose a dimensionless number, the cell Thiele modulus, as a more useful metric for determining solution convergence than element size alone. Finally, we use the cell Thiele modulus to examine convergence criteria for obtaining clinically useful activation patterns for applications such as patient-specific modeling where the total activation time is known a priori.},
	doi = {10.3389/fphys.2015.00217},
	url = {http://journal.frontiersin.org/article/10.3389/fphys.2015.00217/abstract},
	author = {K. P. {Vincent} and M. J. {Gonzales} and Andrew K. {Gillette} and C. T. {Villongco} and Pezzuto, Simone and J. H. {Omens} and M. J. {Holst} and Andrew D. {McCulloch}}
}
@article {Simula.simula.2704,
	title = {Increased Membrane Capacitance Is the Dominant Mechanism of Stretch-Dependent Conduction Slowing in the Rabbit Heart: a Computational Study},
	journal = {Cellular and Molecular Bioengineering},
	volume = {8},
	year = {2015},
	pages = {237-246},
	publisher = { },
	abstract = {Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mech- anisms remain unclear. Previous experimental and modeling studies have investigated some of these mechanisms, including stretch-activated membrane currents, reduced gap junctional conductance, and altered cell membrane capacitance. In order to quantify the relative contributions of these mechanisms, we combined a monomain model of rabbit ventricular electrophysiology with a hyperelastic model of passive ventricular mechanics. After a simplied geometric model with prescribed homogeneous deformation had been used to t model parameters and charcterize individual MEF mechanisms, a 3D model of the rabbit left and right ventricles was compared with experimental measurements from optical electrical mapping studies in the isolated rabbit heart. The model was in ated to an end-diastolic pressure of 30 mmHg, resulting in epicardial strains comparable to those measured in the anterior left ventricular free wall. While the e ects of stretch activated channels did alter epicardial conduction velocity, an increase in cellular capacitance was required to explain previously reported experimental results. The new results suggest that for large strains, various mechanisms can combine and produce a biphasic relationship between strain and conduction velocity. However, at the moderate strains generated by high end-diastolic pressure, a stretch- induced increase in myocyte membrane capacitance is the dominant driver of conduction slowing during ventricular volume loading.},
	author = {Bernardo Lino {de Oliveira} and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch}}
}
@misc {morotti2015ranolazine,
	title = {Ranolazine Prevents Phase-3 Early Afterdepolarizations in Human Atrial Myocytes by Inhibiting Na Current Non-Equilibrium Reactivation},
	howpublished = {Biophysical Society annual meeting},
	year = {2015},
	month = {01/27/2015},
	pages = {195a{\textendash}196a},
	publisher = {Elsevier},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@article {Simula.simula.2384,
	title = {Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback.},
	journal = {Journal of Biomechanical Engineering},
	volume = {136},
	year = {2014},
	publisher = {ASME Digital Collection},
	author = {Pfeiffer, E. and Tangney, J. and Omens, J. and Andrew D. {McCulloch}}
}
@article {23680,
	title = {Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {76},
	year = {2014},
	pages = {265-274},
	publisher = {Academic Press},
	author = {Pfeiffer, ER and Wright, AT and Andrew G {Edwards} and Stowe, JC and McNall, K and Tan, J and Niesman, I and Patel, HH and Roth, DM and Omens, JH and Andrew D. {McCulloch}}
}
@article {23355,
	title = {Computational modeling of subcellular transport and signaling},
	journal = {Current Opinion in Structural Biology},
	volume = {25},
	year = {2014},
	month = {Feb},
	pages = {92{\textendash}97},
	publisher = {Department of Bioengineering and Medicine, University of California San Diego, CA, USA.},
	abstract = {Numerous signaling processes in the cell are controlled in microdomains that are defined by cellular structures ranging from nm to μm in size. Recent improvements in microscopy enable the resolution and reconstruction of these micro domains, while new computational methods provide the means to elucidate their functional roles. Collectively these tools allow for a biophysical understanding of the cellular environment and its pathological progression in disease. Here we review recent advancements in microscopy, and subcellular modeling on the basis of reconstructed geometries, with a special focus on signaling microdomains that are important for the excitation contraction coupling in cardiac myocytes.},
	doi = {10.1016/j.sbi.2014.01.006},
	url = {http://dx.doi.org/10.1016/j.sbi.2014.01.006},
	author = {Johan Elon {Hake} and Peter M. {Kekenes-Huskey} and Andrew D. {McCulloch}}
}
@article {Simula.simula.1594,
	title = {Improved Discretisation and Linearisation of Active Tension in Strongly Coupled Cardiac Electro-Mechanics Simulations},
	journal = {Computer Methods in Biomechanics and Biomedical Engineering},
	volume = {17},
	number = {6},
	year = {2014},
	pages = {604-15},
	publisher = { },
	abstract = {Mathematical models of cardiac electro-mechanics typically consist of three tightly coupled parts: systems of ordinary differential equations describing electro-chemical reactions and cross-bridge dynamics in the muscle cells, a system of partial differential equations modelling the propagation of the electrical activation through the tissue and a nonlinear elasticity problem describing the mechanical deformations of the heart muscle. The complexity of the mathematical model motivates numerical methods based on operator splitting, but simple explicit splitting schemes have been shown to give severe stability problems for realistic models of cardiac electro-mechanical coupling. The stability may be improved by adopting semi-implicit schemes, but these give rise to challenges in updating and linearising the active tension. In this paper we present an operator splitting framework for strongly coupled electro-mechanical simulations and discuss alternative strategies for updating and linearising the active stress component. Numerical experiments demonstrate considerable performance increases from an update method based on a generalised Rush-Larsen scheme and a consistent linearisation of active stress based on the first elasticity tensor.},
	author = {Sundnes, Joakim and Wall, Samuel and Osnes, Harald and Thorvaldsen, Tom and Andrew D. {McCulloch}}
}
@inproceedings {23356,
	title = {A Markov-State Model for the Regulation of the Sarcoplasmic Reticulum Ca2+ ATPase by Phospholamban},
	journal = {Annual meeting in Biophysical society},
	volume = {106},
	year = {2014},
	month = {01/2014},
	publisher = {Elsevier},
	abstract = {Compelling evidence suggests that reduced sarcoplasmic reticulum (SR) Ca 2+ uptake via\&nbsp;the SR Ca 2+ ATPase (SERCA) is a major contributor to the development of Ca 2+ signaling\&nbsp;abnormalities in heart failure, and equally important as other known contributors to impaired\&nbsp;Ca 2+ handling.},
	author = {Peter M. {Kekenes-Huskey} and Andrew G {Edwards} and Johan Elon {Hake} and Anushka P. {Michailova} and Andrew J. {McCammon} and Andrew D. {McCulloch}}
}
@misc {23410,
	title = {Multi-Scale Modeling of the Failing Heart: From Mouse to Man},
	howpublished = {Simula-UiO-UCSD Summer School in Cardiac Modeling},
	year = {2014},
	type = {Keynote talk},
	author = {Andrew D. {McCulloch}}
}
@article {23336,
	title = {Non-equilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle},
	journal = {Circulation: Arrhythmia and Electrophysiology},
	volume = {7},
	year = {2014},
	pages = {1205-1213},
	publisher = {Lippincott Williams \& Wilkins (United States)},
	address = {Worldwide},
	author = {Andrew G {Edwards} and Grandi, Eleonora and Johan Elon {Hake} and Patel, Sonia and Li, Pan and Miyamoto, Shigeki and Jeffrey H. {Omens} and Joan Heller {Brown} and Donald M. {Bers} and Andrew D. {McCulloch}}
}
@article {23347,
	title = {A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII},
	journal = {The Journal of physiology},
	volume = {592},
	year = {2014},
	month = {03/2014},
	pages = {1181-1197},
	publisher = {Wiley-Blackwell},
	author = {Morotti, S and Andrew G {Edwards} and Andrew D. {McCulloch} and Donald M. {Bers} and Grandi, Eleonora}
}
@article {23683,
	title = {A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII},
	journal = {The Journal of Physiology},
	volume = {592},
	year = {2014},
	pages = {1181-1197},
	publisher = {John Wiley \& Sons},
	author = {Morotti, S and Andrew G {Edwards} and Andrew D. {McCulloch} and Donald M. {Bers} and Grandi, Eleonora}
}
@article {23340,
	title = {Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia},
	journal = {Frontiers in Pharmacology},
	volume = {5},
	year = {2014},
	publisher = {Frontiers Media S.A.},
	author = {Kevin P {Vincent} and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {23681,
	title = {Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia},
	journal = {Frontiers in Pharmacology},
	volume = {5},
	year = {2014},
	publisher = {Frontiers Media SA},
	author = {Kevin P {Vincent} and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@inbook {Simula.simula.2290,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (6th Edition)},
	booktitle = {Cardiac Electrophysiology: From Cell to Bedside },
	year = {2013},
	month = {2013},
	pages = {33.1-33.10},
	publisher = {Elsevier Science},
	organization = {Elsevier Science},
	edition = {6},
	chapter = {33},
	isbn = {9781455728565},
	author = {Anushka P. {Michailova} and Andrew G {Edwards} and Johan Elon {Hake} and Hoshijima, Masahiko and Andrew D. {McCulloch}},
	editor = {Zipes, Douglas and Jalife, Jose}
}
@article {Simula.simula.2284,
	title = {Molecular and Subcellular-Scale Modeling of Nucleotide Diffusion in the Cardiac Myofilament Lattice},
	journal = {Biophysical Journal},
	volume = {105},
	number = {9},
	year = {2013},
	pages = {2130},
	doi = {10.1016/j.bpj.2013.09.020},
	author = {Peter M. {Kekenes-Huskey} and Liao, Tao and Andrew K. {Gillette} and Johan Elon {Hake} and Zhang, Yongjie and Anushka P. {Michailova} and Andrew D. {McCulloch} and Andrew J. {McCammon}}
}
@article {Simula.simula.2388,
	title = {Patient-Specific Models of Cardiac Biomechanics},
	journal = {Journal of Computational Physics},
	volume = {244},
	year = {2013},
	pages = {4-21},
	doi = {10.1016/j.jcp.2012.09.015},
	author = {Krishnamurthy, Adarsh and Christopher T. {Villongco} and Chuang, Joyce and Lawrence R. {Frank} and Nigam, Vishal and Belezzuoli, Ernest and Stark, Paul and David E. {Krummen} and Narayan, Sanjiv and Jeffrey H. {Omens} and Andrew D. {McCulloch}}
}
@article {23684,
	title = {The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias},
	journal = {Expert opinion on therapeutic targets},
	volume = {17},
	year = {2013},
	pages = {889-993},
	publisher = {Informa UK, Ltd. London},
	author = {Westenbrink, Daan and Andrew G {Edwards} and Andrew D. {McCulloch} and Joan Heller {Brown}}
}
@article {Simula.simula.1878,
	title = {A Three-Dimensional Finite Element Model of Human Atrial Anatomy: New Methods for Cubic Hermite Meshes With Extraordinary Vertices},
	journal = {Medical Image Analysis},
	volume = {17},
	number = {5},
	year = {2013},
	pages = {525-537},
	keywords = {Workshop},
	author = {Matthew J. {Gonzales} and Sturgeon, Gregory and Krishnamurthy, Adarsh and Johan Elon {Hake} and Jonas, Rene and Stark, Paul and Rappel, Wouter-Jan and Sanjiv M. {Narayan} and Zhang, Yongjie and William P. {Segars} and Andrew D. {McCulloch}}
}
@misc {Simula.simula.1428,
	title = {Modeling Calcium Dynamics in Realistic Rabbit Ventricular Myocytes With Several Transverse Tubules},
	year = {2012},
	author = {Peter M. {Kekenes-Huskey} and Johan Elon {Hake} and Cheng, Yuhui and Michael J. {Holst} and Frank B. {Sachse} and John H. {Bridge} and Andrew D. {McCulloch} and Andrew J. {McCammon} and Anushka P. {Michailova}}
}
@misc {Simula.simula.1410,
	title = {Modeling Calcium Sparks in a Three-Dimensional Reconstruction of a Cardiac Calcium Release Unit},
	year = {2012},
	author = {Johan Elon {Hake} and Andrew G {Edwards} and Yu, Z. and Peter M. {Kekenes-Huskey} and Anushka P. {Michailova} and Andrew J. {McCammon} and Michael J. {Holst} and Hoshijima, Masahiko and Andrew D. {McCulloch}}
}
@article {Simula.simula.1318,
	title = {Modeling Cardiac Calcium Sparks in a Three-Dimensional Reconstruction of a Calcium Release Unit},
	journal = {The Journal of Physiology},
	volume = {590},
	number = {18},
	year = {2012},
	month = {Sept},
	pages = {4403-4422},
	author = {Johan Elon {Hake} and Andrew G {Edwards} and Yu, Z. and Peter M. {Kekenes-Huskey} and Anushka P. {Michailova} and Andrew J. {McCammon} and Michael J. {Holst} and Hoshijima, Masahiko and Andrew D. {McCulloch}}
}
@article {Simula.simula.1722,
	title = {Modeling Effects of L-Type Ca2+ Current and Na+-Ca2+ Exchanger on Ca2+ Trigger Flux in Rabbit Myocytes With Realistic T-Tubule Geometries},
	journal = {Frontiers in Physiology},
	volume = {3},
	year = {2012},
	pages = {351},
	keywords = {Workshop},
	author = {Peter M. {Kekenes-Huskey} and Cheng, Yuhui and Johan Elon {Hake} and Frank B. {Sachse} and John H. {Bridge} and Michael J. {Holst} and Andrew J. {McCammon} and Andrew D. {McCulloch} and Anushka P. {Michailova}}
}
@article {Slow-Calcium-Depolarization-Calcium,
	title = {Slow Calcium-Depolarization-Calcium Waves May Initiate Fast Local Depolarization Waves in Ventricular Tissue},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {110},
	number = {2-3},
	year = {2012},
	month = {July 24},
	pages = {295-304},
	abstract = {Intercellular calcium waves in cardiac myocytes are a well-recognized, if incompletely understood, phenomenon. In a	variety of preparations, investigators have reported multi-cellular calcium waves or triggered propagated contractions, but the	mechanisms of propagation and pathological importance of these events remain unclear. Here, we review existing experimental data and present a computational approach to investigate the mechanisms of multi-cellular calcium wave propagation. Over the past 50 years, the standard modeling paradigm for excitable cardiac tissue	has seen increasingly detailed models of the dynamics of individual cells coupled in tissue solely by intercellular and interstitial current flow. Although very successful, this modeling regime has been unable to capture two important phenomena: 1) the slow intercellular calcium waves observed experimentally, and 2) how intercellular calcium events resulting in delayed after depolarizations at the cellular level could overcome a source-sink mismatch to initiate depolarization waves in tissue. In this paper, we introduce a mathematical model with subcellular spatial resolution, in which we allow both inter- and intracellular current flow and calcium diffusion. In simulations of coupled cells employing this model, we observe: a) slow inter-cellular calcium waves propagating at about 0.1 mm/s, b) faster Calcium-Depolarization-Calcium (CDC) waves, traveling at about 1 mm/s, and c) CDC- waves that can set off fast depolarization-waves (50 cm/s) in tissue with varying gap-junction conductivity.},
	author = {Tveito, Aslak and Glenn T. {Lines} and Andrew G {Edwards} and Maleckar, Molly and Anushka P. {Michailova} and Johan Elon {Hake} and Andrew D. {McCulloch}}
}
@misc {Simula.simula.1414,
	title = {βAR-Stimulation Causes EADs But Not DADs in Pre-Failure CAMKIIδC Transgenic Myocytes},
	howpublished = {Biophysical Society annual meeting},
	year = {2012},
	author = {Andrew G {Edwards} and Johan Elon {Hake} and Joan Heller {Brown} and Andrew D. {McCulloch}}
}
@article {Simula.SC.644,
	title = {On Defining Candidate Drug Characteristics for Long-QT},
	journal = {Mathematical Biosciences and Engineering},
	volume = {8},
	number = {3},
	year = {2011},
	pages = {861-873},
	abstract = {Mutations of the SCN5A gene can significantly alter the function of cardiac myocyte sodium channels leading to increased risk of ventricular arrhythmia. Several gain-of-function mutations associated with long QT intervals result in a persistent late current that prolongs the cardiac action potential. Over the past decade, Markov models of the action potential of wild type and mutant cardiac cells have been developed. The effects of drugs on mutant cells have also been incorporated into some of these models. It is the purpose of this paper to predict the effects on sodium currents and whole cell action potentials of theoretical drugs targeting the mutant sodium channel. Our aim is to compute advantageous properties of a hypothetical drug by deriving Markov model parameters of the drug action that: (a) restores the steady-state open probability of the mutant channel to that of normal wildtype channels; and (b) minimizes the difference between whole cell currents in drugged mutant and wildtype cells. The difference in the electrochemical state vector of the cell can be measured in a norm taking all components and their dynamical properties into account. Measured with this norm, the difference between the state of the mutant and wild type cell was reduced by a factor of 36 after the drug was introduced and by factors of 4 over mexitiline and 25 over lidocaine. The results suggest the potential to synthesize more effective drugs based on mechanisms of action of existing compounds.},
	author = {Tveito, Aslak and Glenn T. {Lines} and Li, Pan and Andrew D. {McCulloch}}
}
@article {Simula.simula.1152,
	title = {Improvement in Pump Function With Endocardial Biventricular Pacing Increases With Activation Time at the Left Ventricular Pacing Site in Failing Canine Hearts},
	journal = {American Journal of Physiology - Heart and Circulatory Physiology},
	volume = {301},
	number = {4},
	year = {2011},
	pages = {H1447-H1455},
	publisher = {American Physiological Society},
	abstract = {Recently, attention has been focused on comparing left ventricular (LV) endocardial (ENDO) with epicardial (EPI) pacing for cardiac resynchronization therapy. However, the effects of ENDO and EPI lead placement at multiple sites have not been studied in failing hearts. We hypothesized that differences in the improvement of ventricular function due to ENDO vs. EPI pacing in dyssynchronous (DYSS) heart failure may depend on the position of the LV lead in relation to the original activation pattern. In six nonfailing and six failing dogs, electrical DYSS was created by atrioventricular sequential pacing of the right ventricular apex. ENDO was compared with EPI biventricular pacing at five LV sites. In failing hearts, increases in the maximum rate of LV pressure change (dP/dt; r = 0.64), ejection fraction (r = 0.49), and minimum dP/dt (r = 0.51), relative to DYSS, were positively correlated (P \&lt; 0.01) with activation time at the LV pacing site during ENDO but not EPI pacing. ENDO pacing at sites with longer activation delays led to greater improvements in hemodynamic parameters and was associated with an overall reduction in electrical DYSS compared with EPI pacing (P \&lt; 0.05). These findings were qualitatively similar for nonfailing hearts. Improvement in hemodynamic function increased with activation time at the LV pacing site during ENDO but not EPI pacing. At the anterolateral wall, end-systolic transmural function was greater with local ENDO compared with EPI pacing. ENDO pacing and intrinsic activation delay may have important implications for management of DYSS heart failure.},
	doi = {10.1152/ajpheart.00295.2011},
	author = {Elliot J. {Howard} and James W. {Covell} and Lawrence J. {Mulligan} and Andrew D. {McCulloch} and Jeffrey H. {Omens}}
}
@article {Simula.simula.1150,
	title = {Multi-Scale Computational Models of Familial Hypertrophic Cardiomyopathy: Genotype to Phenotype},
	journal = {Journal of the Royal Society Interface},
	volume = {8},
	year = {2011},
	note = {Published online at http://rsif.royalsocietypublishing.org/content/early/2011/08/04/rsif.2011.0184.full},
	publisher = {The Royal Society},
	abstract = {Familial hypertrophic cardiomyopathy (FHC) is an inherited disorder affecting roughly one in 500 people. Its hallmark is abnormal thickening of the ventricular wall, leading to serious complications that include heart failure and sudden cardiac death. Treatment is complicated by variation in the severity, symptoms and risks for sudden death within the patient population. Nearly all of the genetic lesions associated with FHC occur in genes encoding sarcomeric proteins, indicating that defects in cardiac muscle contraction underlie the condition. Detailed biophysical data are increasingly available for computational analyses that could be used to predict heart phenotypes based on genotype. These models must integrate the dynamic processes occurring in cardiac cells with properties of myocardial tissue, heart geometry and haemodynamic load in order to predict strain and stress in the ventricular walls and overall pump function. Recent advances have increased the biophysical detail in these models at the myofilament level, which will allow properties of FHC-linked mutant proteins to be accurately represented in simulations of whole heart function. The short-term impact of these models will be detailed descriptions of contractile dysfunction and altered myocardial strain patterns at the earliest stages of the disease-predictions that could be validated in genetically modified animals. Long term, these multi-scale models have the potential to improve clinical management of FHC through genotype-based risk stratification and personalized therapy.},
	doi = {10.1098/rsif.2011.0184},
	author = {Stuart G. {Campbell} and Andrew D. {McCulloch}}
}
@misc {Simula.simula.964,
	title = {A Stochastic Model of the Ryanodine Receptor Featuring Coupled Gating and Competitive Binding of Luminal and Cytosolic Ca2+ and Mg2+},
	year = {2011},
	author = {Johan Elon {Hake} and William E. {Louch} and Haugen, K. and Sjaastad, Ivar and Ole M. {Sejersted} and Andrew D. {McCulloch} and Anushka P. {Michailova} and Glenn T. {Lines}}
}
@article {Simula.sc.1192,
	title = {Cardiac Myocyte Force Development During Differentiation and Maturation},
	journal = {Annals of the New York Academy of Sciences},
	volume = {1188},
	number = {1},
	year = {2010},
	pages = {121-127},
	publisher = {NCBI},
	doi = {10.1111/j.1749-6632.2009.05091.x},
	author = {Jeffrey G. {Jacot} and Kita-Matsuo, Hiroko and Karen A. {Wei} and H. S. Vincent {Chen} and Jeffrey H. {Omens} and Mercola, Mark and Andrew D. {McCulloch}}
}
@inbook {Simula.simula.76,
	title = {A Computational Framework for Patient-Specific Multi-Scale Cardiac Modeling},
	booktitle = {Patient-Specific Modeling of the Cardiovascular System; Technology-Driven Personalized Medicine},
	year = {2010},
	pages = {202-223},
	publisher = {Springer},
	organization = {Springer},
	chapter = {12},
	abstract = {Systems biology has introduced new paradigms in science by switching from a reductionist point of view to a more integrative approach toward the study of \-systems. As researchers over the past years have produced an extraordinary wealth of knowledge on human physiology, we now aim at integrating this knowledge to decipher the intimate relationships between the different components and scales that form the delicate balance in physiological systems. Our aim is to study the heart.},
	isbn = {978-1-4419-6690-2},
	author = {Aguado-Sierra, Jazmin and Fred V. {Lionetti} and Hunt, Darlene and Christopher T. {Villongco} and Gonzales, Matt and Stuart G. {Campbell} and Andrew D. {McCulloch}}
}
@article {Simula.simula.68,
	title = {Coupling of Adjacent Tropomyosins Enhances Cross-Bridge-Mediated Cooperative Activation in a Markov Model of the Cardiac Thin Filament},
	journal = {Biophysical Journal},
	volume = {98},
	number = {10},
	year = {2010},
	month = {May},
	pages = {2254-2264},
	abstract = {We developed a Markov model of cardiac thin filament activation that accounts for interactions among nearest-neighbor regulatory units (RUs) in a spatially explicit manner. Interactions were assumed to arise from structural coupling of adjacent tropomyosins (Tms), such that Tm shifting within each RU was influenced by the Tm status of its neighbors. Simulations using the model demonstrate that this coupling is sufficient to produce observed cooperativity in both steady-state and dynamic force-Ca(2+) relationships. The model was further validated by comparison with reported responses under various conditions including inhibition of myosin binding and the addition of strong-binding, non-force-producing myosin fragments. The model also reproduced the effects of 2.5 mM added P(i) on Ca(2+)-activated force and the rate of force redevelopment measured in skinned rat myocardial preparations. Model analysis suggests that Tm-Tm coupling potentiates the activating effects of strongly-bound cross-bridges and contributes to force-Ca(2+) dynamics of intact cardiac muscle. The model further predicts that activation at low Ca(2+) concentrations is cooperatively inhibited by nearest neighbors, requiring Ca(2+) binding to >25\% of RUs to produce appreciable levels of force. Without excluding other putative cooperative mechanisms, these findings suggest that structural coupling of adjacent Tm molecules contributes to several properties of cardiac myofilament activation.},
	doi = {10.1016/j.bpj.2010.02.010},
	author = {S. G. {Campbell} and Fred V. {Lionetti} and K. S. {Campbell} and Andrew D. {McCulloch}}
}
@article {Simula.sc.1188,
	title = {Determination of Three-Dimensional Ventricular Strain Distributions in Gene-Targeted Mice Using Tagged MRI},
	journal = {Magnetic Resonance in Medicine},
	volume = {64},
	number = {5},
	year = {2010},
	pages = {1281-1288},
	publisher = {John Wiley \& Sons},
	doi = {10.1002/mrm.22547},
	author = {Zemljic-Harpf, Alice and Robert S. {Ross} and Lawrence R. {Frank} and Andrew D. {McCulloch} and Jeffrey H. {Omens}}
}
@inproceedings {Simula.acdc.74,
	title = {GPU Accelerated Cardiac Electrophysiology},
	journal = {Proceedings of the International Conference on Applied Parallel Computing},
	year = {2010},
	type = {1},
	abstract = {Computational models of cardiac electrophysiology require the integration of large and complex systems of ordinary differential equations. This poses special challenges on a GPU architecture owing to the large numbers of state variables required to describe the detailed biophysics of the ion channels in the cardiac muscle cells. We describe a system for generating efficient CUDA C from high level mathematical expressions and their solution within large three-dimensional, anatomically realistic multi-scale models of whole heart electrical activation. Significant performance improvements over CPU clusters are presented.},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@article {Simula.sc.1184,
	title = {Numerical Analysis of Ca2+ Signaling in Rat Ventricular Myocytes With Realistic Transverse-Axial Tubular Geometry and Inhibited Sarcoplasmic Reticulum},
	journal = {PLoS Computational Biology},
	volume = {6},
	number = {10},
	year = {2010},
	pages = {e1000972},
	publisher = {PubMed Central},
	doi = {doi:10.1371/journal.pcbi.1000972},
	author = {Cheng, Y. and Yu, Z. and Hoshijima, M. and Michael J. {Holst} and Andrew D. {McCulloch} and Andrew J. {McCammon} and Anushka P. {Michailova}}
}
@inproceedings {Simula.acdc.60,
	title = {Source-to-Source Optimization of CUDA C for GPU Accelerated Cardiac Cell Modeling},
	journal = {Proceedings of Euro-Par 2010},
	year = {2010},
	type = {Conference},
	abstract = {Large and complex systems of ordinary differential equations (ODEs) arise in diverse areas of science and engineering, and pose special challenges on a streaming processor owing to the large amount of state they manipulate. We describe a set of domain-specific source transformations on CUDA C that improved performance by \&times;6.7 on a system of ODEs arising in cardiac electrophysiology running on the nVidia GTX-295, without requiring expert knowledge of the GPU. Our transformations should apply to a wide range of reaction-diffusion systems.},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@article {Simula.simula.72,
	title = {Systems Approaches and Algorithms for Discovery of Combinatorial Therapies},
	journal = {Wiley Interdisciplinary Reviews: Systems Biology and Medicine},
	volume = {2},
	number = {2},
	year = {2010},
	pages = {93},
	abstract = {Effective therapy of complex diseases requires control of highly nonlinear complex networks that remain incompletely characterized. In particular, drug intervention can be seen as control of cellular network activity. Identification of control parameters presents an extreme challenge due to the combinatorial explosion of control possibilities in combination therapy and to the incomplete knowledge of the systems biology of cells. In this review paper, we describe the main current and proposed approaches to the design of combinatorial therapies, including the heuristic methods used now by clinicians and alternative approaches suggested recently by several authors. New approaches for designing combinations arising from systems biology are described. We discuss in special detail the design of algorithms that identify optimal control parameters in cellular networks based on a quantitative characterization of control landscapes, maximizing utilization of incomplete knowledge of the state and structure of intracellular networks. The use of new technology for high{-}throughput measurements is key to these new approaches to combination therapy and essential for the characterization of control landscapes and implementation of the algorithms. Combinatorial optimization in medical therapy is also compared with the combinatorial optimization of engineering and materials science and similarities and differences are delineated.},
	doi = {10.1002/wsbm.51},
	author = {Jacob D. {Feala} and Cortes, Jorge and Phillip M. {Duxbury} and Piermarocchi, Carlo and Andrew D. {McCulloch} and Paternostro, Giovanni}
}
@article {Simula.simula.66,
	title = {Ventricular Dilation and Electrical Dyssynchrony Synergistically Increase Regional Mechanical Non-Uniformity But Not Mechanical Dyssynchrony; a Computational Model},
	journal = {Circulation: Heart Failure},
	volume = {3},
	number = {4},
	year = {2010},
	month = {May},
	pages = {528-536},
	abstract = {Background Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. Methods and Results All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97\pm0.004, 0.010\pm0.002, and 78\pm1 milliseconds, respectively. With dilation alone, CURE decreased 2.0\pm0.07\%, ISF increased 58\pm47\%, and WTpeak increased 31\pm3\%. With dyssynchronous activation alone, CURE decreased 15\pm0.6\%, ISF increased 14-fold (\pm3), and WTpeak increased 121\pm4\%. With the combination of dilation and dyssynchronous activation, CURE decreased 23\pm0.8\%, ISF increased 20-fold (\pm5), and WTpeak increased 147\pm5\%. Conclusions Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.},
	author = {J. H. {Omens} and Andrew D. {McCulloch} and L. J. {Mulligan}}
}
@article {Simula.sc.1190,
	title = {Ventricular Dilation and Electrical Dyssynchrony Synergistically Increase Regional Mechanical Non-Uniformity But Not Mechanical Dyssynchrony: a Computational Model},
	journal = {Circulation: Heart Failure},
	volume = {3},
	number = {4},
	year = {2010},
	pages = {528-536},
	publisher = {American Heart Association},
	doi = {10.1161/CIRCHEARTFAILURE.109.862144},
	author = {Jeffrey H. {Omens} and Andrew D. {McCulloch} and Lawrence J. {Mulligan}}
}
@article {Simula.sc.1198,
	title = {Effect of Transmurally Heterogeneous Myocyte Excitation-contraction Coupling on Canine Left Ventricular Electromechanics},
	journal = {Experimental Physiology},
	volume = {94},
	number = {5},
	year = {2009},
	pages = {541-552},
	publisher = {BioMedCentral},
	doi = {10.1113/expphysiol.2008.044057},
	author = {S. G. {Campbell} and Howard, E. and Aguado-Sierra, Jazmin and B. A. {Coppola} and J. H. {Omens} and L. J. {Mulligan} and Andrew D. {McCulloch}}
}
@misc {Simula.sc.1138,
	title = {GPU Accelerated Electrophysiology Simulations},
	howpublished = {Talk, poster at the 2009 ACM/IEEE Conference on Supercomputing (SC 2009)},
	year = {2009},
	month = {November},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@misc {Simula.sc.1136,
	title = {GPU Accelerated Electrophysiology Simulations.},
	howpublished = {Talk, Poster at GPU Technology conference, San Jose, California},
	year = {2009},
	month = {October},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@inproceedings {Simula.sc.1134,
	title = {GPU Accelerated Electrophysiology Simulations},
	journal = {Proceedings of the 2009 ACM/IEEE Conference on supercomputing (SC 2009)},
	year = {2009},
	type = {Conference},
	abstract = {Numerical simulations of cellular membranes are useful for basic science and increasingly for clinical diagnostic and therapeutic applications. A common bottleneck arises from solving large stiff systems of ODEs at thousands of integration points in a three-dimensional whole organ model. When performing a modern electrophysiogy simulation on a single conventional core, the ODE bottleneck consumed 99.4\% of the running time. Using an nVidia GTX 295 GPU, we reduced the time to 2\%, eliminating the bottleneck. This speedup comes at a small loss in accuracy, due to the use of single precision. By comparison, a multithreaded implementation running on the CPU yielded a speedup of 3.3 only. We are currently investigating the new bottleneck-a PDE solver. We plan to present results at the conference demonstrating the benefits of hybrid execution, whereby the PDE solver runs as multiple threads on the front end CPU. This choice balances development costs against performance.},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@inproceedings {Simula.sc.1132,
	title = {GPU Accelerated Solvers for ODEs Describing Cardiac Membrane Equations},
	journal = {Proceeding of the GPU technology Conference},
	year = {2009},
	type = {Conference},
	abstract = {Mathematical models describing cellular membranes form the basis of whole tissue models to describe the electrical activity of entire organs, such as the heart. Numerical simulations based on these models are useful for both basic science and increasingly for clinical diagnostic and therapeutic applications such as targeting ablation therapy for atrial arrhythmias, defibrillator design and cardiac resynchronization therapy. A common bottleneck in such simulations arises from solving large stiff systems of ordinary differential equations (ODEs) thousands of times for numerous integration points (representing cells) throughout a three-dimensional tissue or organ model. For some electrophysiology simulations, over 80\% of the time is spent solving these systems of ODEs. While a cluster provides the required interactive response time to solve the ODEs, a desktop sized platform would enhance usability of the software in a laboratory setting. The audience will benefit by learning how a real-world, complex, HPC application can directly benefit by the use of CUDA technology. Participants will learn which optimization techniques yielded the best performance results on an actual application. We will also explore the benefits and limits of the use of single precision in certain scientific applications.},
	author = {Fred V. {Lionetti} and Andrew D. {McCulloch} and Baden, Scott}
}
@article {Simula.sc.1196,
	title = {Hypertrophic Gene Expression Induced by Chronic Stretch of Excised Mouse Heart Muscle},
	journal = {Mol Cell Biomech.},
	volume = {6},
	number = {3},
	year = {2009},
	pages = {145-159},
	publisher = {PubMed Central},
	author = {A. M. {Raskin} and Hoshijima, M. and Swanson, E. and Andrew D. {McCulloch} and J. H. {Omens}}
}
@article {Simula.sc.1194,
	title = {Metabolism As Means for Hypoxia Adaptation: Metabolic Profiling and Flux Balance Analysis},
	journal = {BMC Systems Biology},
	volume = {3},
	number = {91},
	year = {2009},
	pages = {3-91},
	publisher = {BioMedCentral},
	doi = {10.1186/1752-0509-3-91},
	author = {Jacob D. {Feala} and Laurence C. {Coquin} and Zhou, Dan and Gabriel G. {Haddad} and Paternostro, Giovanni and Andrew D. {McCulloch}}
}
@article {Simula.sc.1200,
	title = {Systems Approaches and Algorithms for Discovery of Combinatorial Therapies},
	journal = {Systems Biology and Medicine},
	volume = {2},
	number = {2},
	year = {2009},
	pages = {181-193},
	publisher = {John Wiley \& Sons},
	doi = {10.1002/wsbm.51},
	author = {J. D. {Feala} and Cortes, J. and Phillip M. {Duxbury} and Piermarocchi, C. and Andrew D. {McCulloch} and Paternostro, G.}
}
@article {Simula.sc.934,
	title = {Cardiac Resynchronization: Insight From Experimental and Computational Models},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {97},
	number = {2-3},
	year = {2008},
	month = {June-July},
	pages = {543-561},
	abstract = {Cardiac resynchronization therapy (CRT) is a promising therapy for heart failure patients with a conduction disturbance, such as left bundle branch block. The aim of CRT is to resynchronize contraction between and within ventricles. However, about 30\% of patients do not respond to this therapy. Therefore, a better understanding is needed for the relation between electrical and mechanical activation. In this paper, we focus on to what extent animal experiments and mathematical models can help in order to understand the pathophysiology of asynchrony to further improve CRT.},
	doi = {10.1016/j.pbiomolbio.2008.02.024},
	author = {Lumens, J. and Vernooy, K. and J. H. {Omens} and L. J. {Mulligan} and Delhaas, T. and Arts, Thomas and Andrew D. {McCulloch} and F. W. {Prinzen}}
}
@article {Simula.sc.930,
	title = {Discovering Regulators of the Drosophila Cardiac Hypoxia Response Using Automated Phenotyping Technology},
	journal = {Annals of the New York Academy of Sciences},
	volume = {1123},
	year = {2008},
	month = {March},
	pages = {169-177},
	abstract = {Necrosis and apoptosis during acute myocardial infarction result in part from the inability of hy- poxic cardiac myocytes to match ATP supply and demand. In contrast, hypoxia-tolerant organisms, such as Drosophila, can rapidly regulate cellular metabolism to survive large oxygen fluctuations. A genetic screen of fly heart function during acute hypoxia can be an unbiased way to discover essential enzymes and novel signaling proteins involved in this response. We have developed a pro- totype to show proof of concept for a genome-scale screen, using computer automation to rapidly gather in vivo hypoxic heart data in adult Drosophila. Our system automatically anesthetizes flies, deposits them on a microscope slide, and locates the heart organ of each fly. The system then applies a hypoxia stimulus, acquires time-space (M-mode) images of the heart walls, and analyzes heart rate and rhythm. The prototype can produce highly controlled measurements of up to 55 flies per hour, which we demonstrated by characterizing the effect of temperature, oxygen con- tent, and genetic background on the hypoxia response. We discuss the possible applications of a genome-wide cardiac phenotype data set in systems biology analyses of hypoxic metabolism, using genome-scale interaction networks and constraint-based metabolic models.},
	doi = {10.1196/annals.1420.019},
	author = {Jacob D. {Feala} and Jeffrey H. {Omens} and Paternostro, Giovanni and Andrew D. {McCulloch}}
}
@misc {Simula.sc.1074,
	title = {Emerging Role for Multi-Scale Modeling in the Biomechanical Device Industry},
	howpublished = {Keynote talk at the 3rd ASME Frontiers in Biomechanical Devices Conference, Irvine, California, USA},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.926,
	title = {Mechanisms of Transmurally Varying Myocyte Electromechanics in an Integrated Computational Model},
	journal = {Philosophical Transactions of the Royal Society A},
	volume = {366},
	number = {1879},
	year = {2008},
	month = {September},
	pages = {3361-3380},
	doi = {10.1098/rsta.2008.0088},
	author = {Stuart G. {Campbell} and Sarah N. {Flaim} and Chae H. {Leem} and Andrew D. {McCulloch}}
}
@misc {Simula.sc.1062,
	title = {Mechanobiology of Normal and Failing Myocardium},
	howpublished = {Talk at the Physiology Department, Oxford University},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1068,
	title = {Mechanosensing and Mechanotransduction in the Myocardium},
	howpublished = {Seminar at the Cardiology Department, Academic Hospital Maastricht, The Netherlands},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1058,
	title = {Multi-Scale Modeling and Systems Biology of Cardiac Regulatory Mechanisms},
	howpublished = {Invited talk at the MEI International Symposium Physiome and Systems Biology for Integrated Life Sciences and Predictive Medicine, San Fransisco},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1088,
	title = {Multi-Scale Modeling of Cardiac Electromechanics},
	howpublished = {Talk at the Biomechanical Engineering Math Seminar, Worchester Polytechnic Institute},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1086,
	title = {Multi-Scale Modeling of Cardiac Electromechanics},
	howpublished = {Talk at the Symposium on Computational Physiology, Experimental Biology 2008, San Diego},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1084,
	title = {Multi-Scale Modeling of Cardiac Mechanoenergetics},
	howpublished = {Talk at the Welcome Trust Physiome Workshop on Multi-scale Modeling of the heart, Auckland, New Zealand},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1064,
	title = {Multi-Scale Modeling of the Heart},
	howpublished = {Invited talk at the NCRR P41 Directors, National Library of Medicine, NIH, Bethesda, Maryland, USA},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1066,
	title = {Multi-Scale Modeling of Ventricular Electromechanics},
	howpublished = {Invited talk at the Cardiovascular System Dynamics Society HVIII Conference, St. Louis, USA},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.1214,
	title = {A Myocardial Lineage Derives From Tbx18 Epicardial Cells},
	journal = {Nature},
	volume = {454},
	year = {2008},
	pages = {104-108},
	author = {Cai, C. L. and Martin, J. and Sun, Y. and Cui, L. and Wang, L. and Ouyang, K. and Yang, L. and Bu, L. and Liang, X. and Zhang, X. and W. B. {Stallcup} and C. P. {Denton} and Andrew D. {McCulloch} and Chen, J. and S. M. {Evans}}
}
@misc {Simula.sc.1060,
	title = {Physiome Research in the USA},
	howpublished = {Invited talk at ICT-BIO, The European Commission, Brussels},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.936,
	title = {The Role of Mechanoelectric Feedback in Vulnerability to Electric Shock},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {97},
	number = {2-3},
	year = {2008},
	month = {June},
	pages = {461-478},
	abstract = {Experimental and clinical studies have shown that ventricular dilatation is associated with increased arrhythmogenesis and elevated defibrillation threshold; however, the underlying mechanisms remain poorly understood. The goal of the present study was to test the hypothesis that 1) stretch-activated channel (SAC) recruitment and 2) geometrical deformations in organ shape and fiber architecture lead to increased arrhythmogenesis by electric shocks following acute ventricular dilatation. To elucidate the contribution of these two factors, the study employed, for the first time, a combined electro-mechanical simulation approach. Acute dilatation was simulated in a model of rabbit ventricular mechanics by raising the LV end-diastolic pressure from 0.6 (control) to 4.2 kPa (dilated). The output of the mechanics model was used in the electrophysiological model. Vulnerability to shocks was examined in the control, the dilated ventricles and in the dilated ventricles that also incorporated currents through SAC as a function of local strain, by constructing vulnerability grids. Results showed that dilatation-induced deformation alone decreased upper limit of vulnerability (ULV) slightly and did not result in increased vulnerability. With SAC recruitment in the dilated ventricles, the number of shock-induced arrhythmia episodes increased by 37\% (from 41 to 56) and low limit of vulnerability (LLV) decreased from 9 to 7 V/cm, while ULV did not change. The heterogeneous activation of SAC caused by the heterogeneous fiber strain in the ventricular walls was the main reason for increased vulnerability to electric shocks since it caused dispersion of electrophysiological properties in the tissue, resulting in postshock unidirectional block and establishment of reentry.},
	doi = {10.1016/j.pbiomolbio.2008.02.020},
	author = {Li, Weihui and Gurev, Viatcheslav and Andrew D. {McCulloch}}
}
@misc {Simula.sc.1070,
	title = {Seminar: Multi-Scale Modeling of the Heart},
	howpublished = {Talk at the MURPA eSeminar, Monash University, Melbourne, Australia},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.1216,
	title = {Substrate Stiffness Affects the Functional Maturation of Neonatal Rat Ventricular Myocytes},
	journal = {Biophysiology Journal},
	volume = {95},
	number = {7},
	year = {2008},
	pages = {3479-3487},
	author = {J. J. {Jacot} and Andrew D. {McCulloch} and J. H. {Omens}}
}
@misc {Simula.sc.1082,
	title = {Systems Biology and Multi-Scale Modeling of the Heart},
	howpublished = {Talk at University of Illinois, Chicago, Department of Physiology and Biophysics},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1078,
	title = {Systems Biology and Multi-Scale Modeling of the Heart},
	howpublished = {Seminar at the University of Washington, Department of Bioengineering},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1080,
	title = {Systems Biology and Multi-Scale Modeling of the Heart},
	howpublished = {Plenary lecture at Pacific Biocomputing Symposium, Kona, Hawaii},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@misc {Simula.sc.1072,
	title = {Towards Image-Based Patient-Specific Multi-Scale Modeling of the Failing Heart},
	howpublished = {Invited talk at the 2008 SIAM Life Sciences Conferences, Session MS35, Montreal, Canada},
	year = {2008},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.1208,
	title = {Arrhythmogenic Consequences of Na+ Channel Mutations in the Transmurally Heterogeneous Mammalian Left Ventricle: Analysis of the I1768V SCN5A Mutation},
	journal = {Heart Rhythm},
	volume = {4},
	number = {6},
	year = {2007},
	pages = {768-778},
	author = {S. N. {Flaim} and Wayne R. {Giles} and Andrew D. {McCulloch}}
}
@article {Simula.sc.1212,
	title = {The Cobalamin Precursor Cobinamide Detoxifies Nitroprusside-Generated Cyanide},
	journal = {Experimental Biology and Medicine},
	volume = {232},
	number = {6},
	year = {2007},
	pages = {789-798},
	author = {K. E. {Broderick} and Balasubramanian, M. and Chan, A. and Potluri, P. and Feala, J. and Belke, Darrell and Andrew D. {McCulloch} and V. S. {Sharma} and R. B. {Pilz} and T. D. {Bigby} and G. R. {Boss}}
}
@article {Simula.sc.1202,
	title = {Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation},
	journal = {Ann. Biomed. Eng.},
	volume = {35},
	number = {1},
	year = {2007},
	pages = {1-18},
	author = {M. L. {Neal} and J. B. {Bassingthwaighte} and J. H. {Omens} and Andrew D. {McCulloch}}
}
@article {Simula.sc.1204,
	title = {Flexibility in Energy Metabolism Supports Hypoxia Tolerance in Drosophila Flight Muscle: Metabolomic and Computational Systems Analysis},
	journal = {Mol Syst Biol.},
	volume = {3},
	number = {99},
	year = {2007},
	author = {J. D. {Feala} and Laurence C. {Coquin} and Andrew D. {McCulloch} and Paternostro, G.}
}
@article {Simula.sc.1206,
	title = {Model-Based Development of Four-Dimensional Wall Motion Measures},
	journal = {Computer Methods in Applied Mechanics and Engineering},
	volume = {196},
	number = {31-32},
	year = {2007},
	pages = {Pages 3061-3069},
	doi = {10.1016/j.cma.2006.06.016},
	author = {C. M. {Ingrassia} and T. P. {Usyk} and Andrew D. {McCulloch} and K. D. {Costa} and J. W. {Holmes}}
}
@article {Simula.sc.1210,
	title = {Modeling Transmural Heterogeneity of KATP Current in Rabbit Ventricular Myocytes},
	journal = {American Journal of Physiology - Cell Physiology},
	volume = {293},
	number = {2},
	year = {2007},
	pages = {C542-C557},
	author = {Anushka P. {Michailova} and Lorentz, W. and Andrew D. {McCulloch}}
}
@misc {Simula.sc.902,
	title = {Multi-Scale Modeling of Cardiac Electromechanical Interactions},
	howpublished = {Talk at CBC Workshop on Biomedical Computing, Simula},
	year = {2007},
	month = {June},
	author = {Andrew D. {McCulloch}}
}
@article {Simula.sc.1236,
	title = {Multiscale Modeling: Physiome Project Standards, Tools, and Databases},
	journal = {IEEE Computer Magazine},
	volume = {39},
	number = {11},
	year = {2006},
	pages = {48-54},
	author = {Peter J. {Hunter} and Li, W. and Andrew D. {McCulloch} and Noble, D.}
}
@article {Simula.sc.1240,
	title = {Myocyte Shearing, Myocardial Sheets, and Microtubules},
	journal = {Circulation Research},
	volume = {98},
	number = {1},
	year = {2006},
	pages = {1-3},
	author = {J. H. {Omens} and Andrew D. {McCulloch}}
}
@article {Simula.sc.1238,
	title = {Role of Diastolic Properties in the Transition to Failure in a Mouse Model of Cardiac Dilatation},
	journal = {American Journal of Physiology - Heart and Circulatory Physiology},
	volume = {291},
	number = {6},
	year = {2006},
	pages = {H2971-2979},
	author = {P. N. {Costandi} and L. R. {Frank} and Andrew D. {McCulloch} and J. H. {Omens}}
}
