Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A-class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg(2.39), His(2.43) and Glu(3.46), which makes a polar lock with T(6.37). These alignments and models provide useful tools for understanding class B GPCR function.

Non-English-speaking defendants in the magistrates court:a comparative study of face-to-face and prison video link interpreter-mediated hearings in England

This study compares interpreter-mediated face-to-face Magistrates Court hearings with those conducted through prison video link in which interpreters are located in court and non- English-speaking defendants in prison. It seeks to examine the impact that the presence of video link has on court actors in terms of interaction and behaviour. The data comprises 11 audio-recordings of face-to-face hearings, 10 recordings of prison video link hearings, semistructured interviews with 27 court actors, and ethnographic observation of hearings as viewed by defendants in Wormwood Scrubs prison in London. The over-arching theme is the pervasive influence of the ecology of the courtroom upon all court actors in interpretermediated hearings and thus on the communication process. Close analysis of the court transcripts shows that their relative proximity to one another can be a determinant of status, interpreting role, mode and volume. The very few legal protocols which apply to interpretermediated cases (acknowledging and ratifying the interpreter, for example), are often forgotten or dispensed with. Court interpreters lack proper training in the specific challenges of court interpreting, whether they are co-present with the defendant or not. Other court actors often misunderstand the interpreter’s role. This has probably come about because courts have adjusted their perceptions of what they think interpreters are supposed to do based on their own experiences of working with them, and have gradually come to accept poor practice (the inability to perform simultaneous interpreting, for example) as the norm. In video link courts, mismatches of sound and image due to court clerks’ failure to adequately track current speakers, poor image and sound quality and the fact that non-English-speaking defendants in pre-and post-court consultations can see and hear interpreters but not their defence advocates are just some of the additional layers of disadvantage and confusion already suffered by non- English-speaking defendants. These factors make it less likely that justice will be done.

The definition, theoretical modelling and empirical research of front-line service employee corporate identity within a UK national grocery retailer:determining the FLE corporate brand identification construct

Over the past forty years the corporate identity literature has developed to a point of maturity where it currently contains many definitions and models of the corporate identity construct at the organisational level. The literature has evolved by developing models of corporate identity or in considering corporate identity in relation to new and developing themes, e.g. corporate social responsibility. It has evolved into a multidisciplinary domain recently incorporating constructs from other literature to further its development. However, the literature has a number of limitations. It remains that an overarching and universally accepted definition of corporate identity is elusive, potentially leaving the construct with a lack of clear definition. Only a few corporate identity definitions and models, at the corporate level, have been empirically tested. The corporate identity construct is overwhelmingly defined and theoretically constructed at the corporate level, leaving the literature without a detailed understanding of its influence at an individual stakeholder level. Front-line service employees (FLEs), form a component in a number of corporate identity models developed at the organisational level. FLEs deliver the services of an organisation to its customers, as well as represent the organisation by communicating and transporting its core defining characteristics to customers through continual customer contact and interaction. This person-to-person contact between an FLE and the customer is termed a service encounter, where service encounters influence a customer’s perception of both the service delivered and the associated level of service quality. Therefore this study for the first time defines, theoretically models and empirically tests corporate identity at the individual FLE level, termed FLE corporate identity. The study uses the services marketing literature to characterise an FLE’s operating environment, arriving at five potential dimensions to the FLE corporate identity construct. These are scrutinised against existing corporate identity definitions and models to arrive at a definition for the construct. In reviewing the corporate identity, services marketing, branding and organisational psychology literature, a theoretical model is developed for FLE corporate identity, which is empirically and quantitatively tested, with FLEs in seven stores of a major national retailer. Following rigorous construct reliability and validity testing, the 601 usable responses are used to estimate a confirmatory factor analysis and structural equation model for the study. The results for the individual hypotheses and the structural model are very encouraging, as they fit the data well and support a definition of FLE corporate identity. This study makes contributions to the branding, services marketing and organisational psychology literature, but its principal contribution is to extend the corporate identity literature into a new area of discourse and research, that of FLE corporate identity

Analyze impact of context information on rate adaptation algorithm in vehicular communication

Nowadays, road safety and traffic congestion are major concerns worldwide. This is why research on vehicular communication is very vital. In static scenarios vehicles behave typically like in an office network where nodes transmit without moving and with no defined position. This paper analyses the impact of context information on existing popular rate adaptation algorithms. Our simulation was done in MATLAB by observing the impact of context information on these algorithms. Simulation was performed for both static and mobile cases.Our simulations are based on IEEE 802.11p wireless standard. For static scenarios vehicles do not move and without defined positions, while for the mobile case, vehicles are mobile with uniformly selected speed and randomized positions. Network performance are analysed using context information. Our results show that in mobility when context information is used, the system performance can be improved for all three rate adaptation algorithms. That can be explained by that with range checking, when many vehicles are out of communication range, less vehicles contend for network resources, thereby increasing the network performances. © 2013 IEEE.

The role of ECL2 in CGRP receptor activation:a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a cal-citonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271-294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed. © 2013 The Authors.

Noise modelling and outlier detection in satellite scatterometer data

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Computer based approaches to managerial decision making:optimism, heuristics and simulation

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Metallocene ethylene-1-octene copolymers:influence of comonomer content on thermo-mechanical, rheological, and thermo-oxidative behaviours before and after melt processing in an internal mixer

The influence of the comonomer content in a series of metallocene-based ethylene-1-octene copolymers (m-LLDPE) on thermo-mechanical, rheological, and thermo-oxidative behaviours during melt processing were examined using a range of characterisation techniques. The amount of branching was calculated from 13C NMR and studies using differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were employed to determine the effect of short chain branching (SCB, comonomer content) on thermal and mechanical characteristics of the polymer. The effect of melt processing at different temperatures on the thermo-oxidative behaviour of the polymers was investigated by examining the changes in rheological properties, using both melt flow and capillary rheometry, and the evolution of oxidation products during processing using infrared spectroscopy. The results show that the comonomer content and catalyst type greatly affect thermal, mechanical and oxidative behaviour of the polymers. For the metallocene polymer series, it was shown from both DSC and DMA that (i) crystallinity and melting temperatures decreased linearly with comonomer content, (ii) the intensity of the ß-transition increased, and (iii) the position of the tan δmax peak corresponding to the a-transition shifted to lower temperatures, with higher comonomer content. In contrast, a corresponding Ziegler polymer containing the same level of SCB as in one of the m-LLDPE polymers, showed different characteristics due to its more heterogeneous nature: higher elongational viscosity, and a double melting peak with broader intensity that occurred at higher temperature (from DSC endotherm) indicating a much broader short chain branch distribution. The thermo-oxidative behaviour of the polymers after melt processing was similarly influenced by the comonomer content. Rheological characteristics and changes in concentrations of carbonyl and the different unsaturated groups, particularly vinyl, vinylidene and trans-vinylene, during processing of m-LLDPE polymers, showed that polymers with lower levels of SCB gave rise to predominantly crosslinking reactions at all processing temperatures. By contrast, chain scission reactions at higher processing temperatures became more favoured in the higher comonomer-containing polymers. Compared to its metallocene analogue, the Ziegler polymer showed a much higher degree of crosslinking at all temperatures because of the high levels of vinyl unsaturation initially present.

Optimisation of two-stage raman converter based on phosphosilicate core fibre:Modelling and experiment

Parameter optimization of a two-stage Raman fibre converters (RFC) based on phosphosilicate core fiber was presented. The optimal operational regime was determined and tolerance of the converter against variations of laser parameters was analyzed. Converter was pumped by ytterbium-doped double-clad fibre laser with a maximum output power of 3.8W at 1061 nm. A phosphosilicate-core RFC with enhanced performance was fabricated using the results of numerical modelling.

A mixture density network approach to modelling and exploiting uncertainty in nonlinear control problems

In nonlinear and stochastic control problems, learning an efficient feed-forward controller is not amenable to conventional neurocontrol methods. For these approaches, estimating and then incorporating uncertainty in the controller and feed-forward models can produce more robust control results. Here, we introduce a novel inversion-based neurocontroller for solving control problems involving uncertain nonlinear systems which could also compensate for multi-valued systems. The approach uses recent developments in neural networks, especially in the context of modelling statistical distributions, which are applied to forward and inverse plant models. Provided that certain conditions are met, an estimate of the intrinsic uncertainty for the outputs of neural networks can be obtained using the statistical properties of networks. More generally, multicomponent distributions can be modelled by the mixture density network. Based on importance sampling from these distributions a novel robust inverse control approach is obtained. This importance sampling provides a structured and principled approach to constrain the complexity of the search space for the ideal control law. The developed methodology circumvents the dynamic programming problem by using the predicted neural network uncertainty to localise the possible control solutions to consider. A nonlinear multi-variable system with different delays between the input-output pairs is used to demonstrate the successful application of the developed control algorithm. The proposed method is suitable for redundant control systems and allows us to model strongly non-Gaussian distributions of control signal as well as processes with hysteresis. © 2004 Elsevier Ltd. All rights reserved.

Reliability modelling and verification of manufacturing processes based on process knowledge management

Reliability modelling and verification is indispensable in modern manufacturing, especially for product development risk reduction. Based on the discussion of the deficiencies of traditional reliability modelling methods for process reliability, a novel modelling method is presented herein that draws upon a knowledge network of process scenarios based on the analytic network process (ANP). An integration framework of manufacturing process reliability and product quality is presented together with a product development and reliability verification process. According to the roles of key characteristics (KCs) in manufacturing processes, KCs are organised into four clusters, that is, product KCs, material KCs, operation KCs and equipment KCs, which represent the process knowledge network of manufacturing processes. A mathematical model and algorithm is developed for calculating the reliability requirements of KCs with respect to different manufacturing process scenarios. A case study on valve-sleeve component manufacturing is provided as an application example of the new reliability modelling and verification procedure. This methodology is applied in the valve-sleeve component manufacturing processes to manage and deploy production resources.

Preparation of a poly(L-lactide-co-caprolactone) copolymer using a novel tin(II) alkoxide initiator and its fiber processing for potential use as an absorbable monofilament surgical suture

A poly(L-lactide-co-caprolactone) copolymer, P(LL-co-CL), of composition 75:25 mol% was synthesized via the bulk ring-opening copolymerization of L-lactide and ε-caprolactone using a novel bis[tin(II) monooctoate] diethylene glycol coordination-insertion initiator, OctSn-OCH2CH2OCH2CH2O-SnOct. The P(LL-co-CL) copolymer obtained was characterized by a combination of analytical techniques, namely nuclear magnetic resonance spectroscopy, gel permeation chromatography, dilute-solution viscometry, differential scanning calorimetry, and thermogravimetric analysis. For processing into a monofilament fiber, the copolymer was melt spun with minimal draw to give a largely amorphous and unoriented as-spun fiber. The fiber's oriented semicrystalline morphology, necessary to give the required balance of mechanical properties, was then developed via a sequence of controlled offline hot-drawing and annealing steps. Depending on the final draw ratio, the fibers obtained had tensile strengths in the region of 200–400 MPa.

A systemic approach to the design of cellular manufacturing systems

Cellular manufacturing is widely acknowledged as one of the key approaches to achieving world-class performance in batch manufacturing operations. The design of cellular manufacturing systems (CMS) is therefore crucial in determining a company's competitiveness. This thesis postulated that, in order to be effective the design of CMS should not only be systematic but also systemic. A systemic design uses the concepts of the body of work known as the 'systems approach' to ensure that a truly effective CMS is defined. The thesis examined the systems approach and created a systemic framework against which existing approaches to the design of CMS were evaluated. The most promising of these, Manufacturing Systems Engineering (MSE), was further investigated using a series of cross-sectional case-studies. Although, in practice, MSE proved to be less than systemic, it appeared to produce significant benefits. This seemed to suggest that CMS design did not need to be systemic to be effective. However, further longitudinal case-studies showed that the benefits claimed were at an operational level not at a business level and also that the performance of the whole system had not been evaluated. The deficiencies identified in the existing approaches to designing CMS were then addressed by the development of a novel CMS design methodology that fully utilised systems concepts. A key aspect of the methodology was the use of the Whole Business Simulator (WBS), a modelling and simulation tool that enabled the evaluation of CMS at operational and business levels. The most contentious aspects of the methodology were tested on a significant and complex case-study. The results of the exercise indicated that the systemic methodology was feasible.