Skerritt, Matthew P.Overview
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Matthew P Skerritt
An introduction to modern mathematical computing with Maple
by Jonathan M Borwein
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9 editions published in 2011 in English and held by 360 WorldCat member libraries worldwide
An introduction to modern mathematical computing with Mathematica®
by Jonathan M Borwein
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7 editions published in 2012 in English and held by 343 WorldCat member libraries worldwide Thirty years ago, mathematical computation was difficult to perform and thus used sparingly. However, mathematical computation has become far more accessible due to the emergence of the personal computer, the discovery of fiberoptics and the consequent development of the modern internet, and the creation of Maple, Mathematica, and Matlab. An Introduction to Modern Mathematical Computing: With Mathematica looks beyond teaching the syntax and semantics of Mathematica and similar programs, and focuses on why they are necessary tools for anyone who engages in mathematics. It is an essential read for mathematicians, mathematics educators, computer scientists, engineers, scientists, and anyone who wishes to expand their knowledge of mathematics. This volume will also explain how to become an "experimental mathematician," and will supply useful information about how to create better proofs. The text covers material in elementary number theory, calculus, multivariable calculus, introductory linear algebra, and visualization and interactive geometric computation. It is intended for upperundergraduate students, and as a reference guide for anyone who wishes to learn to use the Mathematica program. Also by J.M. Borwein and M.B. Skerritt: An Introduction to Modern Mathematical Computing: With Maple c2011, ISBN: 9781461401216, 216 p. and 81 color illustrations
ELUCIDATION OF THE MECHANISMS OF GATING IN THE Kv4 3 VOLTAGESENSITIVE POTASSIUM CHANNEL
by Matthew P Skerritt
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1 edition published in 2009 in English and held by 1 WorldCat member library worldwide The molecular and biophysical mechanisms by which Kv4 voltagesensitive K+ channels respond to adjustments in membrane voltage are presently unresolved. With respect to inactivation gating, there is strong evidence that Shakerlike N and P/Ctype mechanisms are not involved. Kv4 channels also display prominent inactivation from preactivated closedstates (closedstate inactivation, CSI), a process which is absent in Shaker (Kv1) channels. As in Shaker, voltage sensitivity in Kv4 is thought to be conferred by positively charged residues localized to the fourth transmembrane segment (S4) of the voltagesensing domain. Kv1 channels possess four basic arginine residues (R1  R4) that are responsible for carrying the majority of gating charge. In Kv4 channels, however, R1 is replaced by a neutral valine at position 287.^In the absence of confirmed mechanisms underlying several gating transitions in Kv4.3, I hypothesized that the S4 voltage sensor domain may serve a primary regulatory role, specifically for the processes of closedstate inactivation and recovery. To test this hypothesis I analyzed the effects of charge elimination at positions 290, 293, and 296 (R2  R4 using Shaker nomenclature) by mutation to the uncharged residue alanine (A). The R to A mutants eliminated individual positive charge while significantly reducing side chain volume and hydrophilic character. Their novel effects on gating may thus have been the result of electrostatic and/or structural perturbations. To address this issue, I next comparatively analyzed arginine to glutamine (R to Q) mutations at the same three positions. This maneuver maintained positive charge elimination of the R to A mutants while partially restoring native side chain volume and hydrophilic properties.^To test whether the lack of charge at position 287 was responsible for noted differences in voltage sensitivity between Kv1 and Kv4.3, I next examined the role of charge addition at the site by mutation to arginine. With all three studies implicating a primary role for the S4 voltage sensor in regulating CSI and recovery, I examined these processes in greater detail through application of elevated extracellular potassium in the presence or absence of KChIP2b. Lastly, I explored the importance of potential electrostatic interactions between S2 and S3 negatively charged residues and positively charged K299 and R302 in S4. Through these studies I conclude that the S4 domain in Kv4.3 is responsible for regulating not only activation and deactivation processes, but also those of closedstate inactivation and recovery. In contrast to Shaker channels, closedstate inactivation appears to possess inherent voltagedependence, or is uniquely coupled to activation.^With the kinetics of deactivation and recovery processes paralleled across the range of conditions analyzed, I suggest that these processes are likely coupled. Finally, it is suggested that S4 may be oriented in the transmembrane electrical field unique from its position in Shaker, so that the transmembrane electrical field resides across R290 in the resting state. Taken together, these results support the argument that a more complicated gating model exists in Kv4.3 as compared to Kv1 channels, and that the regulation of this gating is determined largely by the S4 voltage sensor domain Audience Level
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Skerritt, M. P.
Skerritt, Matt.
Skerritt, Matthew.
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