Joseph Tranquillo

Microelectrode study of the genesis of the monophasic action potential by contact electrode technique.

Monophasic Action Potential Genesis. Introduction: Despite widespread use of the contact electrode for recording monophasic action potentials (MAPs) in both clinical and experimental research, the mechanism underlying the genesis of the contact MAP remains unproven. The “Franz hypothesis” assumes that the MAP is driven by a current source originating at the boundary between cells depolarized by the MAP electrode pressure and normal cells immediately adjacent to it. To date, no direct experimental data exist to support this hypothesis.

Three-dimensional Propagation in Mathematic Models: Integrative Model of the Mouse Heart

Computer models have been used to study cardiac conduction since the late 1970s. 1 At that time, computational power limited investigations to simple geometries corresponding to single fibers or monolayer sheets of cells. With the evolution of computer technologies, computational models of the heart have become three-dimensional and increasingly more realistic, 2 3 4 allowing a wider range of investigations to elucidate fundamental relations of a set of biophysic parameters and the underlying potential distributions and current flow.

Analytical model of extracellular potentials in a tissue slab with a finite bath

Extracellular potentials are often used to assess the activation and repolarization of transmembrane action potentials in cardiac tissue under a variety of experimental conditions. An analytical model of the extracellular potentials arising from a planar wavefront propagating in a three-dimensional slab of cardiac tissue with a variably thick adjacent volume conductor or bath is presented. Starting with the transmembrane potential, the model yields the extracellular potentials at various points in the bath and inside tissue. The results show that the analytical model produces signal timecourses with trivial computational costs that are similar to those computed from a full reaction-diffusion bidomain model with different bath thicknesses for tissue with uniform properties and for tissue with an abrupt ionic inhomogeneity.

Computing correlation integral with the Euclidean distance normalized by the embedding dimension

The Grassberger-Procaccia method is revisited in this paper with a modified approach to compute the correlation integral through a Euclidean distance measure normalized by the embedding dimension. The performance of the suggested modification is assessed using three different types of signals, including Lorenz attractor, mechanical vibrations of helicopter flight, and biological data of animal sleep EEG. Results have shown consistent improvements over the original approach when the normalized Euclidean distance measure is used-correlation integrals for different embedding dimensions not only converge faster in scaling radius but also are more uniformly clustered within the same region. The implementation of the suggested modification is straightforward and resultant correlation integrals and linearly scaling regions for correlation dimension estimation are less sensitive to the varying embedding dimension.

Action Potential and QT Prolongation Not Sufficient to Cause Torsade de Pointes: Role of Action Potential Triangulation

Syncope and sudden death resulting from Torsade de Pointes (TdP) are very uncommon but major adverse drug effects. Prolongation of the QT interval is the most widely used marker of this potential. Minimal prolongation of the QT interval has been the basis for termination of drug development programs, the imposition of significant restrictions on prescription or withdrawal of drugs from the market. In the absence of drug treatment or electrolyte abnormality, QT interval prolongation is a common finding in clinical electrocardiography. In this setting, syncope and sudden death are largely restricted to individuals with inherited mutations of cardiac ion channel genes. Roden1 and Hondeghem2 have summarized compelling arguments that simple QT interval prolongation is a poor marker for proarrhythmic susceptibility. The many shortcomings of the long QT-proarrhythmia hypothesis include:

Entrepreneurship and ABET accreditation: How and where does it fit?

As a result of economic and workforce trends, there is a strong interest among policy makers and educational stakeholders in graduating more engineers with entrepreneurship skills and an entrepreneurial mindset. Given the role that ABET accreditation takes in shaping undergraduate engineering curriculum, wide adoption of entrepreneurship education could be driven by demonstrating the manner in which its outcomes align with accreditation mandates. This work in progress describes research taking place that is designed to develop a robust rationale for aligning entrepreneurship education with ABET Criterion 3 a-k, and to provide examples of the manner in which entrepreneurship-related outcomes can meet these criteria.

Biomedical Signals and Systems

Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time and frequency analysis and filters. Embedded within each chapter are examples from the biological world, ranging from medical devices to cell and molecular biology. While the focus of the book is on the theory of analog signals and systems, many chapters also introduce the corresponding topics in the digital realm. Although some derivations appear, the focus is on the concepts and how to apply them. Throughout the text, systems vocabulary is introduced which will allow the reader to read more advanced literature and communicate with scientist and engineers. Homework and Matlab simulation exercises are presented at the end of each chapter and challenge readers to not only perform calculations and simulations but also to recognize the real-world signals and systems around them. Table of Contents: Preface / Acknowledgments / Introduction / System Types / System Models / Laplace Transform / Block Diagrams / Stability / Feedback / System Response / Control / Time Domain Analysis / Frequency Domain Analysis / Filters / Authors Biography

Collision-Based Spiral Acceleration in Cardiac Media: Roles of Wavefront Curvature and Excitable Gap

We have previously shown in experimental cardiac cell monolayers that rapid point pacing can convert basic functional reentry (single spiral) into a stable multiwave spiral that activates the tissue at an accelerated rate. Here, our goal is to further elucidate the biophysical mechanisms of this rate acceleration without the potential confounding effects of microscopic tissue heterogeneities inherent to experimental preparations. We use computer simulations to show that, similar to experimental observations, single spirals can be converted by point stimuli into stable multiwave spirals. In multiwave spirals, individual waves collide, yielding regions with negative wavefront curvature. When a sufficient excitable gap is present and the negative-curvature regions are close to spiral tips, an electrotonic spread of excitatory currents from these regions propels each colliding spiral to rotate faster than the single spiral, causing an overall rate acceleration. As observed experimentally, the degree of rate acceleration increases with the number of colliding spiral waves. Conversely, if collision sites are far from spiral tips, excitatory currents have no effect on spiral rotation and multiple spirals rotate independently, without rate acceleration. Understanding the mechanisms of spiral rate acceleration may yield new strategies for preventing the transition from monomorphic tachycardia to polymorphic tachycardia and fibrillation.

MATLAB for Engineering and the Life Sciences

Abstract In recent years, the life sciences have embraced simulation as an important tool in biomedical research. Engineers are also using simulation as a powerful step in the design process. In both arenas, Matlab has become the gold standard. It is easy to learn, flexible, and has a large and growing userbase. MATLAB for Engineering and the Life Sciences is a self-guided tour of the basic functionality of MATLAB along with the functions that are most commonly used in biomedical engineering and other life sciences. Although the text is written for undergraduates, graduate students and academics, those in industry may also find value in learning MATLAB through biologically inspired examples. For instructors, the book is intended to take the emphasis off of learning syntax so that the course can focus more on algorithmic thinking. Although it is not assumed that the reader has taken differential equations or a linear algebra class, there are short introductions to many of these concepts. Following a short ...

Can we trust the transgenic mouse? insights from computer simulations

Over the past several decades, the mouse has gained prominence in the cardiac electrophysiology literature as the animal model of choice. Using computer models of the mouse and human ECG, this paper is a step toward understanding when themouse succeeds and fails to mimic functional changes resulting from disease states and drug interactions.