A frequency-independent boundary element method for scattering by two-dimensional screens and apertures

We propose and analyse a hybrid numerical-asymptotic $hp$ boundary element method for time-harmonic scattering of an incident plane wave by an arbitrary collinear array of sound-soft two-dimensional screens. Our method uses an approximation space enriched with oscillatory basis functions, chosen to capture the high frequency asymptotics of the solution. Our numerical results suggest that fi�xed accuracy can be achieved at arbitrarily high frequencies with a frequency-independent computational cost. Our analysis does not capture this observed behaviour completely, but we provide a rigorous frequency-explicit error analysis which proves that the method converges exponentially as the number of degrees of freedom $N$ increases, and that to achieve any desired accuracy it is sufficient to increase $N$ in proportion to the square of the logarithm of the frequency as the frequency increases (standard boundary element methods require $N$ to increase at least linearly with frequency to retain accuracy). We also show how our method can be applied to the complementary "breakwater" problem of propagation through an aperture in an infinite sound-hard screen

Ohio Upholds Traditional Exception to General Rule of Corporate Successor Nonliability

The purpose of this Note is to carefully analyze the Ohio Supreme Court\u27s reasoning in Welco and its implications. Part II discusses corporate successor liability in general, and then focuses narrowly on the mere continuation exception to successor nonliability. Part III breaks down the case itself, presenting the facts, procedure, and reasoning of the majority and dissent. Finally, Part IV analyzes the court\u27s refusal to expand the mere continuation exception, suggesting that had the court chosen to expand the the exception, the advantages of a cash-for-assets acquisition in Ohio would have been lost

Editor\u27s Introduction

David Langdon highlights the articles present in the 40th anniversary issue of the Journal of Northeast Historical Archaeology

A Descriptive Study Utilizing Grounded Theory: The Moral-Reasoning Process of Coaches

p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Times New Roman ; }p.MsoBodyText, li.MsoBodyText, div.MsoBodyText { margin: 0in 0in 6pt; font-size: 12pt; font-family: Times New Roman ; }span.BodyTextChar { }div.Section1 { page: Section1; } As an interested reader of the educational literature on moral development I have become intrigued by the significance of moral-reasoning in sport. After nearly four decades of coach education in Canada concern is being voiced about the apparent erosion of moral values amongst many coaches or, at the very least, their moral ambivalence. A database search of the literature and research findings on moral development generally espouses some sort of stage theory (Haan, 1977; Kohlberg, 1958; Weiss, 1987). Through a separate line of inquiry one can find an interest in understanding how coaches learn. Gilbert and Trudel (1999) have researched extensively the impact of experiential learning (Kolb, 1984) and critical reflection (Schön, 1991) on the learning process specifically related to coaching. The intersection of these two lines of research leads to the question of how the moral-reasoning of coaches, in competitive situations, is mediated by the specific sport-based context of their experience. p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Times New Roman ; }p.MsoBodyText, li.MsoBodyText, div.MsoBodyText { margin: 0in 0in 6pt; font-size: 12pt; font-family: Times New Roman ; }span.BodyTextChar { }div.Section1 { page: Section1; } This study utilized the varied cartographic visual mapping techniques developed by Clarke (2005) and described as situational maps, relational analyses, social worlds/arenas maps, etc., which provided the method for analysing the data from interviews and artefacts. Participants’ experiences were explored using self-identified challenging moral dilemmas through a qualitative methodology employing the grounded theory method following the situational analysis (Clarke, 2005) theoretical framework. Grounded theory by its very design is a conceptual framework. Situational analysis provides some structural concepts that, thanks to Clarke (2005), now exist in the literature but it is still conceptual in nature. @font-face { font-family: Times ; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Times New Roman ; }p.MsoBodyText, li.MsoBodyText, div.MsoBodyText { margin: 0in 0in 6pt; font-size: 12pt; font-family: Times New Roman ; }span.BodyTextChar { }div.Section1 { page: Section1; } The results indicate that the seemingly eclectic approach to moral-reasoning exhibited by coaches is in fact a complex system of analysis that leads to solutions. The process considers public perception, concepts of universal opportunity as well as short and long-term impact on the specific sport as well as the sport community as a whole. Based the results I was able to develop a model explaining the moral-reasoning employed by the participants in this study. Further research may determine if this can be generalized to a broader segment of the coaching profession. I hope that this model will help coach educators develop better programs to teach coaches about making moral decisions

Dysphagia in Stroke: A New Solution

Dysphagia is extremely common following stroke, affecting 13%–94% of acute stroke sufferers. It is associated with respiratory complications, increased risk of aspiration pneumonia, nutritional compromise and dehydration, and detracts from quality of life. While many stroke survivors experience a rapid return to normal swallowing function, this does not always happen. Current dysphagia treatment in Australia focuses upon prevention of aspiration via diet and fluid modifications, compensatory manoeuvres and positional changes, and exercises to rehabilitate paretic muscles. This article discusses a newer adjunctive treatment modality, neuromuscular electrical stimulation (NMES), and reviews the available literature on its efficacy as a therapy for dysphagia with particular emphasis on its use as a treatment for dysphagia in stroke. There is a good theoretical basis to support the use of NMES as an adjunctive therapy in dysphagia and there would appear to be a great need for further well-designed studies to accurately determine the safety and efficacy of this technique

A model of estrogen-related gene expression reveals non-linear effects in transcriptional response to tamoxifen

SynthSys is a Centre for Integrative Systems Biology (CISB) funded by BBSRC and EPSRC, reference BB/D019621/1.Background: Estrogen receptors alpha (ER) are implicated in many types of female cancers, and are the common target for anti-cancer therapy using selective estrogen receptor modulators (SERMs, such as tamoxifen). However, cell-type specific and patient-to-patient variability in response to SERMs (from suppression to stimulation of cancer growth), as well as frequent emergence of drug resistance, represents a serious problem. The molecular processes behind mixed effects of SERMs remain poorly understood, and this strongly motivates application of systems approaches. In this work, we aimed to establish a mathematical model of ER-dependent gene expression to explore potential mechanisms underlying the variable actions of SERMs. Results: We developed an equilibrium model of ER binding with 17 beta-estradiol, tamoxifen and DNA, and linked it to a simple ODE model of ER-induced gene expression. The model was parameterised on the broad range of literature available experimental data, and provided a plausible mechanistic explanation for the dual agonism/antagonism action of tamoxifen in the reference cell line used for model calibration. To extend our conclusions to other cell types we ran global sensitivity analysis and explored model behaviour in the wide range of biologically plausible parameter values, including those found in cancer cells. Our findings suggest that transcriptional response to tamoxifen is controlled in a complex non-linear way by several key parameters, including ER expression level, hormone concentration, amount of ER-responsive genes and the capacity of ER-tamoxifen complexes to stimulate transcription (e. g. by recruiting co-regulators of transcription). The model revealed non-monotonic dependence of ER-induced transcriptional response on the expression level of ER, that was confirmed experimentally in four variants of the MCF-7 breast cancer cell line. Conclusions: We established a minimal mechanistic model of ER-dependent gene expression, that predicts complex non-linear effects in transcriptional response to tamoxifen in the broad range of biologically plausible parameter values. Our findings suggest that the outcome of a SERM's action is defined by several key components of cellular micro-environment, that may contribute to cell-type-specific effects of SERMs and justify the need for the development of combinatorial biomarkers for more accurate prediction of the efficacy of SERMs in specific cell types.Publisher PDFPeer reviewe

Kinetic modelling of in vitro data of PI3K, mTOR1, PTEN enzymes and on-target inhibitors Rapamycin, BEZ235, and LY294002

The phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin-1 (mTOR1) are two key targets for anti-cancer therapy. Predicting the response of the PI3K/AKT/mTOR1 signalling pathway to targeted therapy is made difficult because of network complexities. Systems biology models can help explore those complexities but the value of such models is dependent on accurate parameterisation. Motivated by a need to increase accuracy in kinetic parameter estimation, and therefore the predictive power of the model, we present a framework to integrate kinetic data from enzyme assays into a unified enzyme kinetic model. We present exemplar kinetic models of PI3K and mTOR1, calibrated on in vitro enzyme data and founded on Michaelis-Menten (MM) approximation. We describe the effects of an allosteric mTOR1 inhibitor (Rapamycin) and ATP-competitive inhibitors (BEZ2235 and LY294002) that show dual inhibition of mTOR1 and PI3K. We also model the kinetics of phosphatase and tensin homolog (PTEN), which modulates sensitivity of the PI3K/AKT/mTOR1 pathway to these drugs. Model validation with independent data sets allows investigation of enzyme function and drug dose dependencies in a wide range of experimental conditions. Modelling of the mTOR1 kinetics showed that Rapamycin has an IC50 independent of ATP concentration and that it is a selective inhibitor of mTOR1 substrates S6K1 and 4EBP1: it retains 40% of mTOR1 activity relative to 4EBP1 phosphorylation and inhibits completely S6K1 activity. For the dual ATP-competitive inhibitors of mTOR1 and PI3K, LY294002 and BEZ235, we derived the dependence of the IC50 on ATP concentration that allows prediction of the IC50 at different ATP concentrations in enzyme and cellular assays. Comparison of the drug effectiveness in enzyme and cellular assays showed that some features of these drugs arise from signalling modulation beyond the on-target action and MM approximation and require a systems-level consideration of the whole PI3K/PTEN/AKT/mTOR1 network in order to understand mechanisms of drug sensitivity and resistance in different cancer cell lines. We suggest that using these models in systems biology investigation of the PI3K/AKT/mTOR1 signalling in cancer cells can bridge the gap between direct drug target action and the therapeutic response to these drugs and their combinations