Effect of Electrode Placement on Defibrillation Threshold and Esophageal Electric Field in Internal Atrial Defibrillation

Atrial fibrillation is the most common heart arrhythmia of clinical significance. Internal cardioversion can be used to restore sinus rhythm; however, the amount of delivered energy elicits intolerable pain. Lowering delivered energy could make implantable cardioverters a promising treatment option. This study simulated cardioversion shocks in a model of the human heart using finite element analysis to determine effects of different electrode placements on defibrillation threshold (DFT) and esophageal electric field (EEF) near the left atrium. Ten right atrial to coronary sinus electrode placements were tested. Small shifts in electrode placements changed DFT by up to 42%, indicating electrode position is an important factor in lowering DFT. A relationship was not discovered between EEF and DFT. If a relationship can be discovered between an alternate EEF or other measure and DFT, electrode placements could be optimized on a patient-specific basis to lower delivered energy to painless or tolerable levels

Variational principles for involutive systems of vector fields

In many relevant cases -- e.g., in hamiltonian dynamics -- a given vector field can be characterized by means of a variational principle based on a one-form. We discuss how a vector field on a manifold can also be characterized in a similar way by means of an higher order variational principle, and how this extends to involutive systems of vector fields.Comment: 31 pages. To appear in International Journal of Geometric Methods in Modern Physics (IJGMMP

Hamiltonization of Nonholonomic Systems and the Inverse Problem of the Calculus of Variations

We introduce a method which allows one to recover the equations of motion of a class of nonholonomic systems by finding instead an unconstrained Hamiltonian system on the full phase space, and to restrict the resulting canonical equations to an appropriate submanifold of phase space. We focus first on the Lagrangian picture of the method and deduce the corresponding Hamiltonian from the Legendre transformation. We illustrate the method with several examples and we discuss its relationship to the Pontryagin maximum principle.Comment: 23 pages, accepted for publication in Rep. Math. Phy

Driving and sustaining culture change in professional sport performance teams: A grounded theory

Objectives As part of the recent upsurge of work on management and organizational factors in elite sports teams, researchers have focused on the team management-led creation and regulation of high performing cultures. The purpose of this study was to therefore add to a recently developed model of culture change best practice in Olympic sports teams, as led and perceived by incoming performance directors, and conceptualize culture change best practice in professional sports teams, as led and perceived by incoming team managers. Design and method A pragmatic research philosophy and corresponding grounded theory methodology were used to generate a practically-meaningful model of this culture change process from the perspective of UK-based professional team managers. Results Perceived best practice in team manager-led culture change was found to involve a finite phase of initial evaluation, planning, and impact adjoined to the enduring management of a holistic, integrated, and dynamic social system. With the former process acting as the catalyst for successful change, this model revealed that optimal change was felt to primarily rely on the constant acquisition, negotiation, and alignment of internal and external stakeholder perceptions. Conclusions Based on the model's principles, the optimization of professional team culture is defined by a manager's initial actions and never definitively achieved but rather constantly constructed and re-constructed in complex social and power dynamics. Beyond providing a conceptual backdrop for continued research in this area, the model is also a tool on which the practice of professional team managers and their supporting sport psychologists can be based

OBDD-Based Representation of Interval Graphs

A graph $G = (V,E)$ can be described by the characteristic function of the edge set $\chi_E$ which maps a pair of binary encoded nodes to 1 iff the nodes are adjacent. Using \emph{Ordered Binary Decision Diagrams} (OBDDs) to store $\chi_E$ can lead to a (hopefully) compact representation. Given the OBDD as an input, symbolic/implicit OBDD-based graph algorithms can solve optimization problems by mainly using functional operations, e.g. quantification or binary synthesis. While the OBDD representation size can not be small in general, it can be provable small for special graph classes and then also lead to fast algorithms. In this paper, we show that the OBDD size of unit interval graphs is $O(\ | V \ | /\log \ | V \ |)$ and the OBDD size of interval graphs is $O(\ | V \ | \log \ | V \ |)$which both improve a known result from Nunkesser and Woelfel (2009). Furthermore, we can show that using our variable order and node labeling for interval graphs the worst-case OBDD size is$\Omega(\ | V \ | \log \ | V \ |)$. We use the structure of the adjacency matrices to prove these bounds. This method may be of independent interest and can be applied to other graph classes. We also develop a maximum matching algorithm on unit interval graphs using$O(\log \ | V \ |)$operations and a coloring algorithm for unit and general intervals graphs using$O(\log^2 \ | V \ |)$ operations and evaluate the algorithms empirically.Comment: 29 pages, accepted for 39th International Workshop on Graph-Theoretic Concepts 201

Collier Heights

This resource was created by the Case Studies class in Spring of 2008 as a Historic District Information Form. It includes data on the neighborhood known as Collier Heights, as well as pertinent newspaper clippings, permits, blueprints, maps, and other primary sources.https://scholarworks.gsu.edu/history_heritagepreservation/1011/thumbnail.jp

Quantitative Genetic Effects of Bottlenecks: Experimental Evidence from a Wild Plant Species, Nigella degenii

Understanding the genetic consequences of changes in population size is fundamental in a variety of contexts, such as adaptation and conservation biology. In the study presented here, we have performed a replicated experiment with the plant Nigella degenii to explore the quantitative genetic effects of a single-founder bottleneck. In agreement with additive theory, the bottleneck reduced the mean (co)variance within lines and caused stochastic, line-specific changes in the genetic (co)variance structure. However, a significant portion of the (co)variance structure was conserved, and 2 characters—leaf and flower (sepal) size—turned out to be positively correlated in all data sets, indicating a potential for correlated evolution in these characters, even after a severe bottleneck. The hierarchical partitioning of genetic variance for flower size was in good agreement with predictions from additive theory, whereas the remaining characters showed an excess of within-line variance and a deficiency of among-line variance. The latter discrepancies were most likely a result of selection, given the small proportion of lines (23%) that remained viable until the end of the experiment. Our results suggest that bottlenecked populations of N. degenii generally have a lower adaptive potential than the ancestral population but also highlight the idiosyncratic nature of bottleneck effects

Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through NUP62, inhibiting host nucleocytoplasmic transport pathways

The herpes simplex virus ICP27 protein is important for the expression and nuclear export of viral mRNAs. Although several binding sites have been mapped along the ICP27 sequence for various RNA and protein partners including the transport receptor TAP of the host cell nuclear transport machinery, several aspects of ICP27 trafficking through the nuclear pore complex remain unclear. We investigated if ICP27 could interact directly with the nuclear pore complex itself, finding that ICP27 directly binds the core nucleoporin Nup62. This is confirmed through co-immunoprecipitation and in vitro binding assays with purified components. Mapping with ICP27 deletion and point mutants further shows that the interaction requires sequences in both the N and C-termini of ICP27. Expression of wildtype ICP27 protein inhibited both classical, importin α/β-dependent and transportin dependent nuclear import. In contrast, an ICP27 point mutant that does not interact with Nup62 had no such inhibitory effect. We suggest that ICP27 association with Nup62 provides additional binding sites at the nuclear pore for ICP27 shuttling thus supporting ICP27-mediated transport. We propose that ICP27 competes with some host cell transport receptors for binding, resulting in inhibition of those host transport pathways

Systems analysis of dynamic transcription factor activity identifies targets for treatment in Olaparib resistant cancer cells

The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly(ADP‐ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA‐mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells. TF activity was monitored in the parental HCC1937 cell line and two distinct resistant cell lines, one with restored wild‐type BRCA1 and one with acquired resistance independent of BRCA1 for 48 h during treatment with Olaparib. Partial least squares discriminant analysis (PLSDA) was used to categorize the three cell types based on TF activity, and network analysis was used to investigate the mechanism of early response to Olaparib in the study cells. NOTCH signaling was identified as a common pathway linked to resistance in both Olaparib‐resistant cell types. Western blotting confirmed upregulation of NOTCH protein, and sensitivity to Olaparib was restored through co‐treatment with a gamma secretase inhibitor. The identification of NOTCH signaling as a common pathway contributing to PARP inhibitor resistance by TRACER indicates the efficacy of transcription factor dynamics in identifying targets for intervention in treatment‐resistant cancer and provides a new method for determining effective strategies for directed chemotherapy. Biotechnol. Bioeng. 2017;114: 2085–2095. © 2017 Wiley Periodicals, Inc.Dynamic cell response to therapy is dependent on the sensitivity of the cells to treatment. In this work, a transcriptional activity cell array (TRACER) was used to measure transcription factor activity dynamics in BRCA‐mutated breast cancer cells during treatment with Olaparib. The dynamic measurements were used to both identify sensitive and resistant cells as well as suggest therapy to resensitize resistant cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137743/1/bit26293_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137743/2/bit26293.pd