The interaction between metabolic disease and ageing

Two of the greatest crises that civilisation faces in the 21st century are the predicted rapid increases in the ageing population and levels of metabolic disorders such as obesity and type 2 diabetes. A growing amount of evidence now supports the notion that energy balance is a key determinant not only in metabolism but also in the process of cellular ageing. Much of genetic evidence for a metabolic activity-driven ageing process has come from model organisms such as worms and flies where inactivation of the insulin receptor signalling cascade prolongs lifespan. At its most simplistic, this poses a conundrum for ageing in humans – can reduced insulin receptor signalling really promote lifespan and does this relate to insulin resistance seen in ageing? In higher animals, caloric restriction studies have confirmed a longer lifespan when daily calorie intake is reduced to 60% of normal energy requirement. This suggests that for humans, it is energy excess which is a likely driver of metabolic ageing. Interventions that interfere with the metabolic fate of nutrients offer a potentially important target for delaying biological ageing.

Problematising L2 listening pedagogy:the potential of process-based listening strategy instruction in the L2 classroom

Listening is typically the first language skill to develop in first language (L1) users and has been recognized as a basic and fundamental tool for communication. Despite the importance of listening, aural abilities are often taken for granted, and many people overlook their dependency on listening and the complexities that combine to enable this multi-faceted skill. When second language (L2) students are learning their new language, listening is crucial, as it provides access to oral input and facilitates social interaction. Yet L2 students find listening challenging, and L2 teachers often lack sufficient pedagogy to help learners develop listening abilities that they can use in and beyond the classroom. In an effort to provide a pedagogic alternative to more traditional and limited L2 listening instruction, this thesis investigated the viability of listening strategy instruction (LSI) over three semesters at a private university in Japan through a qualitative action research (AR) intervention. An LSI program was planned and implemented with six classes over the course of three AR phases. Two teachers used the LSI with 121 learners throughout the project. Following each AR phase, student and teacher perceptions of the methodology were investigated via questionnaires and interviews, which were primary data collection methods. Secondary research methods (class observations, pre/post-semester test scores, and a research journal) supplemented the primary methods. Data were analyzed and triangulated for emerging themes related to participants’ perceptions of LSI and the viability thereof. These data showed consistent positive perceptions of LSI on the parts of both learners and teachers, although some aspects of LSI required additional refinement. This project provided insights on LSI specific to the university context in Japan and also produced principles for LSI program planning and implementation that can inform the broader L2 education community.

Modeling the peptide-T cell receptor interaction by the comparative molecular similarity indices analysis-soft independent modeling of class analogy technique

A set of 38 epitopes and 183 non-epitopes, which bind to alleles of the HLA-A3 supertype, was subjected to a combination of comparative molecular similarity indices analysis (CoMSIA) and soft independent modeling of class analogy (SIMCA). During the process of T cell recognition, T cell receptors (TCR) interact with the central section of the bound nonamer peptide; thus only positions 4−8 were considered in the study. The derived model distinguished 82% of the epitopes and 73% of the non-epitopes after cross-validation in five groups. The overall preference from the model is for polar amino acids with high electron density and the ability to form hydrogen bonds. These so-called “aggressive” amino acids are flanked by small-sized residues, which enable such residues to protrude from the binding cleft and take an active role in TCR-mediated T cell recognition. Combinations of “aggressive” and “passive” amino acids in the middle part of epitopes constitute a putative TCR binding motif

An analysis of police interview discourse and its role(s) in the judicial process

This study analyses the current role of police-suspect interview discourse in the England & Wales criminal justice system, with a focus on its use as evidence. A central premise is that the interview should be viewed not as an isolated and self-contained discursive event, but as one link in a chain of events which together constitute the criminal justice process. It examines: (1) the format changes undergone by interview data after the interview has taken place, and (2) how the other links in the chain – both before and after the interview – affect the interview-room interaction itself. It thus examines the police interview as a multi-format, multi-purpose and multi-audience mode of discourse. An interdisciplinary and multi-method discourse-analytic approach is taken, combining elements of conversation analysis, pragmatics, sociolinguistics and critical discourse analysis. Data from a new corpus of recent police-suspect interviews, collected for this study, are used to illustrate previously unaddressed problems with the current process, mainly in the form of two detailed case studies. Additional data are taken from the case of Dr. Harold Shipman. The analysis reveals several causes for concern, both in aspects of the interaction in the interview room, and in the subsequent treatment of interview material as evidence, especially in the light of s.34 of the Criminal Justice and Public Order Act 1994. The implications of the findings for criminal justice are considered, along with some practical recommendations for improvements. Overall, this study demonstrates the need for increased awareness within the criminal justice system of the many linguistic factors affecting interview evidence.

Fiber bragg gratings:advances in fabrication process and tools

Successful commercialization of a technology such as Fiber Bragg Gratings requires the ability to manufacture devices repeatably, quickly and at low cost. Although the first report of photorefractive gratings was in 1978 it was not until 1993, when phase mask fabrication was demonstrated, that this became feasible. More recently, draw tower fabrication on a production level and grating writing through the polymer jacket have been realized; both important developments since they preserve the intrinsic strength of the fiber. Potentially the most significant recent development has been femtosecond laser inscription of gratings. Although not yet a commercial technology, it provides the means of writing multiple gratings in the optical core providing directional sensing capability in a single fiber. Femtosecond processing can also be used to machine the fiber to produce micronscale slots and holes enhancing the interaction between the light in the core and the surrounding medium. © 2011 Bentham Science Publishers Ltd. All rights reserved.

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.