@article {, title = {Excitable dynamics in neural and cardiac systems}, journal = {Communications in Nonlinear Science and Numerical Simulation}, volume = {86}, year = {2020}, month = {07/2020}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:hMsQuOkrut0C}, author = {Roberto Barrio and Stephen Coombes and Mathieu Desroches and Flavio Fenton and Stefan Luther and Esther Pueyo} } @article {, title = {Electromechanical vortex filaments during cardiac fibrillation}, journal = {Nature}, volume = {555}, year = {2018}, pages = {667+}, abstract = {

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities5,6\ that are associated with three-dimensional scroll waves7\ are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control14,15,16\ of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

}, doi = {https://doi.org/10.1038/nature26001}, author = {Jan Christoph and M. Chebbok and Carl Richter and Johannes Schr{\"o}der-Schetelig and Philip Bittihn and Seth Stein and Ilija Uzelac and FLAVIO H. FENTON and Gerd Hasenfuss and Robert F. Gilmour and Stefan Luther} } @article {, title = {Effects of model error on cardiac electrical wave state reconstruction using data assimilation}, journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science}, volume = {27}, year = {2017}, pages = {093911}, abstract = {

Reentrant electrical scroll waves have been shown to underlie many cardiac arrhythmias, but the inability to observe locations away from the heart surfaces and the restriction of observations to only one or two state variables have made understanding arrhythmia mechanisms challenging. Recently, we showed that data assimilation from spatiotemporally sparse surrogate observations could be used to reconstruct a reliable time series of state estimates of reentrant cardiac electrical waves including unobserved variables in one and three spatial dimensions. However, real cardiac tissue is unlikely to be described accurately by mathematical models because of errors in model formulation and parameterization as well as intrinsic but poorly described spatial heterogeneity of electrophysiological properties in the heart. Here, we extend our previous work to assess how model error affects the accuracy of cardiac state estimates achieved using data assimilation with the Local Ensemble Transform Kalman Filter. We focus on one-dimensional states of discordant alternans characterized by significant wavelength oscillations. We demonstrate that data assimilation can provide high-quality estimates under a wide range of model error conditions, ranging from varying one or more parameter values to using an entirely different model to generate the truth state. We illustrate how multiplicative and additive inflation can be used to reduce error in the state estimates. Even when the truth state contains underlying spatial heterogeneity, we show that using a homogeneous model in the data assimilation algorithm can achieve good results. Overall, we find data assimilation to be a robust approach for reconstructing complex cardiac electrical states corresponding to arrhythmias even in the presence of model error.

}, issn = {1054-1500}, doi = {10.1063/1.4999603}, url = {http://aip.scitation.org/doi/10.1063/1.4999603}, author = {LaVigne, Nicholas S. and Holt, Nathan and Hoffman, Matthew J. and Cherry, Elizabeth M.} } @article {, title = {Efficient parameterization of cardiac action potential models using a genetic algorithm}, journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science}, volume = {27}, year = {2017}, pages = {093922}, abstract = {

Finding appropriate values for parameters in mathematical models of cardiac cells is a challenging task. Here, we show that it is possible to obtain good parameterizations in as little as 30{\textendash}40 s when as many as 27 parameters are fit simultaneously using a genetic algorithm and two flexible phenomenological models of cardiac action potentials. We demonstrate how our implementation works by considering cases of {\textquotedblleft}model recovery{\textquotedblright} in which we attempt to find parameter values that match model-derived action potential data from several cycle lengths. We assess performance by evaluating the parameter values obtained, action potentials at fit and non-fit cycle lengths, and bifurcation plots for fidelity to the truth as well as consistency across different runs of the algorithm. We also fit the models to action potentials recorded experimentally using microelectrodes and analyze performance. We find that our implementation can efficiently obtain model parameterizations that are in good agreement with the dynamics exhibited by the underlying systems that are included in the fitting process. However, the parameter values obtained in good parameterizations can exhibit a significant amount of variability, raising issues of parameter identifiability and sensitivity. Along similar lines, we also find that the two models differ in terms of the ease of obtaining parameterizations that reproduce model dynamics accurately, most likely reflecting different levels of parameter identifiability for the two models.

}, issn = {1054-1500}, doi = {10.1063/1.5000354}, url = {http://aip.scitation.org/doi/10.1063/1.5000354}, author = {Cairns, Darby I. and Fenton, Flavio H. and Cherry, E. M.} } @article {, title = {Estimability Analysis and Optimal Design in Dynamic Multi-scale Models of Cardiac Electrophysiology}, journal = {Journal of Agricultural, Biological, and Environmental Statistics}, year = {2016}, pages = {1{\textendash}16}, author = {Shotwell, Matthew S and Gray, Richard A} } @conference {, title = {Experience Report: Model-Based Test Automation of a Concurrent Flight Software Bus}, booktitle = {2016 IEEE 27th International Symposium on Software Reliability Engineering (ISSRE)}, year = {2016}, month = {Oct}, keywords = {aerospace computing, API, application program interfaces, Automation, Computer architecture, Concurrency, Concurrent computing, concurrent design, concurrent flight software bus, concurrent publisher-subscriber architecture style, concurrent system testing, Context, Flight Software, MBT technique, message passing, Microsoft Spec Explorer MBT tool, middleware, Model Based Testing, model-based test automation, NASA, NASA Core Flight Software software bus module, program testing, Publish-Subscribe, safety-critical software, safety-critical system, Software, software architecture, SUT, system-under-test, test case analysis, Testing}, doi = {10.1109/ISSRE.2016.47}, author = {D. Ganesan and M. Lindvall and S. Hafsteinsson and R. Cleaveland and S. L. Strege and W. Moleski} } @article {, title = {An extensible formal semantics for UML activity diagrams}, journal = {arXiv preprint arXiv:1604.02386}, year = {2016}, author = {Daw, Zamira and Cleaveland, Rance} } @conference {, title = {An Extensible Operational Semantics for {UML} Activity Diagrams}, booktitle = {Software Engineering and Formal Methods - 13th International Conference, {SEFM} 2015, York, UK, September 7-11, 2015. Proceedings}, year = {2015}, doi = {10.1007/978-3-319-22969-0\_25}, url = {https://doi.org/10.1007/978-3-319-22969-0\_25}, author = {Zamira Daw and Rance Cleaveland} }