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Biomedical Engineering and Bioengineering Commons™
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Full-Text Articles in Biomedical Engineering and Bioengineering
Positive Rate-Dependent Action Potential Prolongation By Modulating Potassium Ion Channels, Candido Cabo
Positive Rate-Dependent Action Potential Prolongation By Modulating Potassium Ion Channels, Candido Cabo
Publications and Research
Pharmacological agents that prolong action potential duration (APD) to a larger extent at slow rates than at the fast excitation rates typical of ventricular tachycardia exhibit reverse rate dependence. Reverse rate dependence has been linked to the lack of efficacy of class III agents at preventing arrhythmias because the doses required to have an anti-arrhythmic effect at fast rates may have pro-arrhythmic effects at slow rates due to an excessive APD prolongation. In this report we show that, in computer models of the ventricular action potential, APD prolongation by accelerating phase 2 repolarization (by increasing IKs) and decelerating …
Insights Into The Binding Mode Of Mek Type-Iii Inhibitors. A Step Towards Discovering And Designing Allosteric Kinase Inhibitors Across The Human Kinome, Zheng Zhao, Lei Xie, Philip E. Bourne
Insights Into The Binding Mode Of Mek Type-Iii Inhibitors. A Step Towards Discovering And Designing Allosteric Kinase Inhibitors Across The Human Kinome, Zheng Zhao, Lei Xie, Philip E. Bourne
Publications and Research
Protein kinases are critical drug targets for treating a large variety of human diseases. Type- III kinase inhibitors have attracted increasing attention as highly selective therapeutics. Thus, understanding the binding mechanism of existing type-III kinase inhibitors provides useful insights into designing new type-III kinase inhibitors. In this work, we have systematically studied the binding mode of MEK-targeted type-III inhibitors using structural systems pharmacology and molecular dynamics simulation. Our studies provide detailed sequence, structure, interaction-fingerprint, pharmacophore and binding-site information on the binding characteristics of MEK type-III kinase inhibitors. We hypothesize that the helix-folding activation loop is a hallmark allosteric binding site …
Toward Measuring Network Aesthetics Based On Symmetry, Zengqiang Chen, Matthias Dehmer, Frank Emmert-Streib, Abbe Mowshowitz, Yongtang Shi
Toward Measuring Network Aesthetics Based On Symmetry, Zengqiang Chen, Matthias Dehmer, Frank Emmert-Streib, Abbe Mowshowitz, Yongtang Shi
Publications and Research
In this exploratory paper, we discuss quantitative graph-theoretical measures of network aesthetics. Related work in this area has typically focused on geometrical features (e.g., line crossings or edge bendiness) of drawings or visual representations of graphs which purportedly affect an observer’s perception. Here we take a very different approach, abandoning reliance on geometrical properties, and apply information-theoretic measures to abstract graphs and networks directly (rather than to their visual representaions) as a means of capturing classical appreciation of structural symmetry. Examples are used solely to motivate the approach to measurement, and to elucidate our symmetry-based mathematical theory of network aesthetics.