All Outputs (90)

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential (2015)
Journal Article

© 2015 Heart Rhythm Society. Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study... Read More about Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression (2015)
Journal Article

© 2015 The Authors. In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM) ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relati... Read More about Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression.

A web portal for in-silico action potential predictions (2015)
Journal Article

© 2015 . Introduction: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch c... Read More about A web portal for in-silico action potential predictions.

Cardiac tissue slices: Preparation, handling, and successful optical mapping (2015)
Journal Article

© 2015 the American Physiological Society. Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and o... Read More about Cardiac tissue slices: Preparation, handling, and successful optical mapping.

Cellular cardiac electrophysiology modeling with Chaste and CellML (2015)
Journal Article

© 2015 Cooper, Spiteri and Mirams. Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac e... Read More about Cellular cardiac electrophysiology modeling with Chaste and CellML.

Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue (2014)
Journal Article

Prediction of Thorough QT study results using action potential simulations based on ion channel screens (2014)
Journal Article

Ten Simple Rules for Effective Computational Research (2014)
Journal Article

Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge (2013)
Journal Article

Introduction Drugs that prolong the QT interval on the electrocardiogram present a major safety concern for pharmaceutical companies and regulatory agencies. Despite a range of assays performed to assess compound effects on the QT interval, QT prolo... Read More about Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge.

Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment (2013)
Journal Article

Introduction: Unwanted drug interactions with ionic currents in the heart can lead to an increased pro-arrhythmic risk to patients in the clinic. It is therefore a priority for safety pharmacology teams to detect block of cardiac ion channels, and ne... Read More about Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment.

Chaste: An Open Source C++ Library for Computational Physiology and Biology (2013)
Journal Article

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac ele... Read More about Chaste: An Open Source C++ Library for Computational Physiology and Biology.

mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study (2013)
Journal Article

Differences in mRNA expression levels have been observed in failing versus non-failing human hearts for several membrane channel proteins and accessory subunits. These differences may play a causal role in electrophysiological changes observed in hum... Read More about mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study.

Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials (2013)
Journal Article

Background and Purpose: Understanding drug effects on the heart is key to safety pharmacology assessment and anti-arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug actio... Read More about Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials.

Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing (2012)
Journal Article

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore h... Read More about Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.

A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt (2012)
Journal Article

The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal ca... Read More about A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt.

Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG (2012)
Journal Article

Human embryonic stem cell-derived cardiomyocytes (hESC-CM) have been proposed as a new model for safety pharmacology. So far, a thorough description of their basic electrophysiology and extensive testing, and mechanistic explanations, of their overal... Read More about Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG.

Is it time for in silico simulation of drug cardiac side effects? (2011)
Journal Article

Cardiac simulation is used to integrate information on drug action to predict side effects on the whole heart. Could simulation begin to replace animal models? © 2011 New York Academy of Sciences.

Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets (2011)
Journal Article

New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Ke... Read More about Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets.

A local sensitivity analysis method for developing biological models with identifiable parameters: Application to cardiac ionic channel modelling (2011)
Journal Article

Computational cardiac models provide important insights into the underlying mechanisms of heart function. Parameter estimation in these models is an ongoing challenge with many existing models being overparameterised. Sensitivity analysis presents a... Read More about A local sensitivity analysis method for developing biological models with identifiable parameters: Application to cardiac ionic channel modelling.

High-throughput functional curation of cellular electrophysiology models (2011)
Journal Article

Effective reuse of a quantitative mathematical model requires not just access to curated versions of the model equations, but also an understanding of the functional capabilities of the model, and the advisable scope of its application. To enable thi... Read More about High-throughput functional curation of cellular electrophysiology models.