Characterization of the structure of RAMP1 by mutagenesis and molecular modeling

Receptor activity modifying proteins (RAMPs) are a family of single-pass transmembrane proteins that dimerize with G-protein-coupled receptors. They may alter the ligand recognition properties of the receptors (particularly for the calcitonin receptor-like receptor, CLR). Very little structural information is available about RAMPs. Here, an ab initio model has been generated for the extracellular domain of RAMP1. The disulfide bond arrangement (Cys 27-Cys82, Cys40-Cys72, and Cys 57-Cys104) was determined by site-directed mutagenesis. The secondary structure (a-helices from residues 29-51, 60-80, and 87-100) was established from a consensus of predictive routines. Using these constraints, an assemblage of 25,000 structures was constructed and these were ranked using an all-atom statistical potential. The best 1000 conformations were energy minimized. The lowest scoring model was refined by molecular dynamics simulation. To validate our strategy, the same methods were applied to three proteins of known structure; PDB:1HP8, PDB:1V54 chain H (residues 21-85), and PDB:1T0P. When compared to the crystal structures, the models had root mean-square deviations of 3.8 Å, 4.1 Å, and 4.0 Å, respectively. The model of RAMP1 suggested that Phe93, Tyr 100, and Phe101 form a binding interface for CLR, whereas Trp74 and Phe92 may interact with ligands that bind to the CLR/RAMP1 heterodimer. © 2006 by the Biophysical Society.

Linking FDI motivation and host economy productivity effects:conceptual and empirical analysis

We develop a taxonomy that relates foreign direct investment (FDI) motivation (technology- and cost-based) to its anticipated effects on host countries domestic productivity. We then empirically examine the effects of FDI into the United Kingdom on domestic productivity, and find that different types of FDI have markedly different productivity spillover effects, which are consistent with the conceptual analysis. The UK gains substantially only from inward FDI motivated by a strong technology-based ownership advantage. As theory predicts, inward FDI motivated by technology-sourcing considerations leads to no productivity spillovers.

Point-by-point inscription of 250-nm-period structure in bulk fused silica by tightly-focused femtosecond UV pulses: experiment and numerical modeling

By conducting point-by-point inscription in a continuously moving slab of a pure fused silica at the optimal depth (170 μm depth below the surface), we have fabricated a 250-nm-period nanostructure with 30 nJ, 300 fs, 1 kHz pulses from frequency-tripled Ti:sapphire laser. This is the smallest value for the inscribed period yet reported, and has been achieved with radical improvement in the quality of the inscribed nanostructures in comparison with previous reports. The performed numerical modeling confirms the obtained experimental results.

Bandwidth management of WiMAX systems and performance modeling

WiMAX has been introduced as a competitive alternative for metropolitan broadband wireless access technologies. It is connection oriented and it can provide very high data rates, large service coverage, and flexible quality of services (QoS). Due to the large number of connections and flexible QoS supported by WiMAX, the uplink access in WiMAX networks is very challenging since the medium access control (MAC) protocol must efficiently manage the bandwidth and related channel allocations. In this paper, we propose and investigate a cost-effective WiMAX bandwidth management scheme, named the WiMAX partial sharing scheme (WPSS), in order to provide good QoS while achieving better bandwidth utilization and network throughput. The proposed bandwidth management scheme is compared with a simple but inefficient scheme, named the WiMAX complete sharing scheme (WCPS). A maximum entropy (ME) based analytical model (MEAM) is proposed for the performance evaluation of the two bandwidth management schemes. The reason for using MEAM for the performance evaluation is that MEAM can efficiently model a large-scale system in which the number of stations or connections is generally very high, while the traditional simulation and analytical (e.g., Markov models) approaches cannot perform well due to the high computation complexity. We model the bandwidth management scheme as a queuing network model (QNM) that consists of interacting multiclass queues for different service classes. Closed form expressions for the state and blocking probability distributions are derived for those schemes. Simulation results verify the MEAM numerical results and show that WPSS can significantly improve the network's performance compared to WCPS.

Combined quality function deployment and logical framework analysis to improve quality of emergency care in Malta

Purpose – The purpose of this paper is to develop an integrated patient-focused analytical framework to improve quality of care in accident and emergency (A&E) unit of a Maltese hospital. Design/methodology/approach – The study adopts a case study approach. First, a thorough literature review has been undertaken to study the various methods of healthcare quality management. Second, a healthcare quality management framework is developed using combined quality function deployment (QFD) and logical framework approach (LFA). Third, the proposed framework is applied to a Maltese hospital to demonstrate its effectiveness. The proposed framework has six steps, commencing with identifying patients’ requirements and concluding with implementing improvement projects. All the steps have been undertaken with the involvement of the concerned stakeholders in the A&E unit of the hospital. Findings – The major and related problems being faced by the hospital under study were overcrowding at A&E and shortage of beds, respectively. The combined framework ensures better A&E services and patient flow. QFD identifies and analyses the issues and challenges of A&E and LFA helps develop project plans for healthcare quality improvement. The important outcomes of implementing the proposed quality improvement programme are fewer hospital admissions, faster patient flow, expert triage and shorter waiting times at the A&E unit. Increased emergency consultant cover and faster first significant medical encounter were required to start addressing the problems effectively. Overall, the combined QFD and LFA method is effective to address quality of care in A&E unit. Practical/implications – The proposed framework can be easily integrated within any healthcare unit, as well as within entire healthcare systems, due to its flexible and user-friendly approach. It could be part of Six Sigma and other quality initiatives. Originality/value – Although QFD has been extensively deployed in healthcare setup to improve quality of care, very little has been researched on combining QFD and LFA in order to identify issues, prioritise them, derive improvement measures and implement improvement projects. Additionally, there is no research on QFD application in A&E. This paper bridges these gaps. Moreover, very little has been written on the Maltese health care system. Therefore, this study contributes demonstration of quality of emergency care in Malta.

Bioactive sol-gel glasses at the atomic scale:the complementary use of advanced probe and computer modeling methods

Sol-gel-synthesized bioactive glasses may be formed via a hydrolysis condensation reaction, silica being introduced in the form of tetraethyl orthosilicate (TEOS), and calcium is typically added in the form of calcium nitrate. The synthesis reaction proceeds in an aqueous environment; the resultant gel is dried, before stabilization by heat treatment. These materials, being amorphous, are complex at the level of their atomic-scale structure, but their bulk properties may only be properly understood on the basis of that structural insight. Thus, a full understanding of their structure-property relationship may only be achieved through the application of a coherent suite of leading-edge experimental probes, coupled with the cogent use of advanced computer simulation methods. Using as an exemplar a calcia-silica sol-gel glass of the kind developed by Larry Hench, in the memory of whom this paper is dedicated, we illustrate the successful use of high-energy X-ray and neutron scattering (diffraction) methods, magic-angle spinning solid-state NMR, and molecular dynamics simulation as components to a powerful methodology for the study of amorphous materials.

A risk-based model for inspection and maintenance of cross-country petroleum pipeline

The existing method of pipeline health monitoring, which requires an entire pipeline to be inspected periodically, is both time-wasting and expensive. A risk-based model that reduces the amount of time spent on inspection has been presented. This model not only reduces the cost of maintaining petroleum pipelines, but also suggests efficient design and operation philosophy, construction methodology and logical insurance plans. The risk-based model uses Analytic Hierarchy Process (AHP), a multiple attribute decision-making technique, to identify the factors that influence failure on specific segments and analyzes their effects by determining probability of risk factors. The severity of failure is determined through consequence analysis. From this, the effect of a failure caused by each risk factor can be established in terms of cost, and the cumulative effect of failure is determined through probability analysis. The technique does not totally eliminate subjectivity, but it is an improvement over the existing inspection method.

The spacing and timing of [a chic] critique

This rejoinder reflects an important step, for me, in a preoccupation with methodology that has provided me with many hours of enjoyable reading, not to mention anxiety. For me the ‘reality’ of the incommensurable nature of paradigms and acceptance of the legitimacy of a range of conceptual and philosophical traditions came late. As a constructionist I find myself on the ‘anything goes’ end of methodology choice. This paper and my main paper ought not to be read as a critique of ‘middle range’ theory, but as a critique of an important and necessary aspect of the way we all seek to inscribe facts and structure our writing. What follows is a reflection of the influence Bruno Latour’s writings have had on my ways of seeing and perhaps an unhealthy emphasis on the small things that combine to produce convincing arguments and ‘facts’.

Contextualising accounts of illness:Notions of responsibility and blame in white and South Asian respondents' accounts of diabetes causation

We undertook a secondary analysis of in-depth interviews with white (n = 32) and Pakistani and Indian (n = 32) respondents who had type 2 diabetes, which explored their perceptions and understandings of disease causation. We observed subtle, but important, differences in the ways in which these respondent groups attributed responsibility and blame for developing the disease. Whereas Pakistani and Indian respondents tended to externalise responsibility, highlighting their life circumstances in general and/or their experiences of migrating to Britain in accounting for their diabetes (or the behaviours they saw as giving rise to it), white respondents, by contrast, tended to emphasise the role of their own lifestyle 'choices' and 'personal failings'. In seeking to understand these differences, we argue for a conceptual and analytical approach which embraces both micro- (i.e. everyday) and macro- (i.e. cultural) contextual factors and experiences. In so doing, we provide a critique of social scientific studies of lay accounts/understandings of health and illness. We suggest that greater attention needs to be paid to the research encounter (that is, to who is looking at whom and in what circumstances) to understand the different kinds of contexts researchers have highlighted in presenting and interpreting their data. © 2007 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

Undue influence and the family home

This book provides a comprehensive analysis of the doctrine of undue influence in the context of the family home and fully incorporates the recent House of Lords ruling in Royal Bank of Scotland v Etridge (No 2) (2001). It is aimed predominantly at the legal practitioner, but will also act as a useful source of reference for academics and students of contract, land law and equity and trusts. Emphasis is placed on claims brought by spouses (usually the wife) seeking to set aside a charge over the matrimonial home made in favour of a lending institution. The role of lenders in this context is also examined in depth, as is the part played by the solicitor acting on behalf of the parties. Apart from providing an exposition of the doctrine and its key elements, the book also gives a broader outlook by examining the Commonwealth experience (notably in Australia, Canada and New Zealand) and suggesting an underlying concept of unconscionability as governing undue influence claims. There is also a separate chapter on remedies, as well as an appendix containing a number of draft pleadings for use by the legal practitioner. In the foreword, the Honourable Mr Justice Neuberger writes: 'Pawlowski and Brown are to be congratulated for having produced a book ...as comprehensive and user-friendly as this volume. Not only have they considered the effect of the authorities in a clear and logical way, but they have also highlighted problems which have yet to be resolved and questions which have yet to be answered ...one of the hallmarks of a good legal book.'

The European Union and the racialization of immigration, 1985-2006

Over the past two decades, the European Union (EU) has played an increasingly influential role in the construction of a de facto common immigration and asylum policy, providing a forum for policy-formulation beyond the scrutiny of national parliaments. The guiding principles of this policy include linking the immigration portfolio to security rather than justice; reaffirming the importance of political, conceptual and organizational borders; and attempting to transfer policing and processing functions to non-EU countries. The most important element, I argue, is the structural racialization of immigration that occurs across the various processes and which escapes the focus of much academic scrutiny. Exploring this phenomenon through the concept of the “racial state,” I examine ways to understand the operations of immigration policy-making at the inter-governmental level, giving particular attention to the ways in which asylum-seekers emerge as a newly racialized group who are both stripped of their rights in the global context and deployed as Others in the construction of national narratives.

Switching and generation of ultrashort pulses using all-fibre devices

Serial and parallel interconnection of photonic devices is integral to the construction of any all-optical data processing system. This thesis presents results from a series of experiments centering on the use of the nonlinear-optical loop mirror (NOLM) switch in architectures for the manipulation and generation of ultrashort pulses. Detailed analysis of soliton switching in a single NOLM and cascade of two NOLM's is performed, centering on primary limitations to device operation, effect of cascading on amplitude response, and impact of switching on the characteristics of incident pulses. By using relatively long input pulses, device failure due to stimulated Raman generation is postponed to demonstrate multiple-peaked switching for the first time. It is found that while cascading leads to a sharpening of the overall switching characteristic, pulse spectral and temporal integrity is not significantly degraded, and emerging pulses retain their essential soliton character. In addition, by including an asymmetrically placed in-fibre Bragg reflector as a wavelength selective loss element in the basic NOLM configuration, both soliton self-switching and dual-wavelength control-pulse switching are spectrally quantised. Results are presented from a novel dual-wavelength laser configuration generating pulse trains with an ultra-low rms inter-pulse-stream timing jitter level of 630fs enabling application in ultrafast switching environments at data rates as high as 130GBits/s. In addition, the fibre NOLM is included in architectures for all-optical memory, demonstrating storage and logical inversion of a 0.5kByte random data sequence; and ultrafast phase-locking of a gain-switched distributed feedback laser at 1.062GHz, the fourteenth harmonic of the system baseband frequency. The stringent requirements for environmental robustness of these architectures highlight the primary weaknesses of the NOLM in its fibre form and recommendations to overcome its inherent drawbacks are presented.

Sales manager problem resolution styles:measure development and an examination of their salesperson-related consequences

Personal selling and sales management play a critical role in the short and long term success of the firm, and have thus received substantial academic interest since the 1970s. Sales research has examined the role of the sales manager in some depth, defining a number of key technical and interpersonal roles which sales managers have in influencing sales force effectiveness. However, one aspect of sales management which appears to remain unexplored is that of their resolution of salesperson-related problems. This study represents the first attempt to address this gap by reporting on the conceptual and empirical development of an instrument designed to measure sales managers' problem resolution styles. A comprehensive literature review and qualitative research study identified three key constructs relating to sales managers' problem resolution styles. The three constructs identified were termed; sales manager willingness to respond, sales manager caring, and sales manager aggressiveness. Building on this, existing literature was used to develop a conceptual model of salesperson-specific consequences of the three problem resolution style constructs. The quantitative phase of the study consisted of a mail survey of UK salespeople, achieving a total sample of 140 fully usable responses. Rigorous statistical assessment of the sales manager problem resolution style measures was undertaken, and construct validity examined. Following this, the conceptual model was tested using latent variable path analysis. The results for the model were encouraging overall, and also with regard to the individual hypotheses. Sales manager problem resolution styles were found individually to have significant impacts on the salesperson-specific variables of role ambiguity, emotional exhaustion, job satisfaction, organisational commitment and organisational citizenship behaviours. The findings, theoretical and managerial implications, limitations and directions for future research are discussed.

Leadership and the negotiation of order in small groups

This thesis is focussed on the role differentiationhypothesis as it relates to small groups (Bales, 1958). The hypothesis is systematically examined, both conceptually and empirically, in the light of the Equilibrium Hypothesis (Bales, 1953) and the Negotiated Order Theory of leadership (e.g. Hosking, 1988). Chapter 1 sketches in a context for the research,which was stimulated by attempts during the 60s and 70s to organise small groups without leaders (the leaderless group, based on isocratic principles). Chapter 2 gives a conceptual and developmental overview of Bales' work, concentrating on the Equilibrium Hypothesis. It is argued that Bales' conceptual approach, if developed, can potentially integrate the disparate small groups and leadership literatures. Chapters 3 and 4 examine the concepts `group', `leader' and `leadership' in terms of the Negotiated Order perspective. In chapter 3 it is argued that two aspects of the concept group need to be taken separately into account; physical attributes and social psychological aspects (the metaphysical glue). It is further argued that a collection of people becomes a group only when they begin to establish a shared sense of social order. In chapter 4 it is argued that leadership is best viewed as a process of negotiation between those who influence and those who are influenced, in the context of shared values about means and ends. It is further argued that leadership is the process by which a shared sense of social order is established and maintained, thus linking the concepts `leadership' and `group' in a single formulation. The correspondences with Bales' approach are discussed at the end of the chapter. Chapters 5 to 8 present a detailed critical description and evaluation of the empirical work which claims to show role differentiation or test the hypothesis, both Bales original work and subsequent studies. It is argued here, that the measurement and analytical procedures adopted by Bales and others, in particular the use of simple means as summaries of group structures, are fundamentally flawed, and that role differentiation in relation to particular identifiable groups has not been demonstrated clearly anywhere in the literature. Chapters 9 to 13 present the empirical work conducted for the thesis. 18 small groups are examined systematically for evidence of role differentiation using an approach based on early sociometry (Moreno, 1934). The results suggest that role differentiation, as described by Bales, does not occur as often as is implied in the literature, and not equivocally in any case. In particular structures derived from Liking are typically distributed or weak. This suggests that one of Bales' principal findings, that Liking varies independently of his other main dimensions, is the product of statistical artifact. Chapter 14 presents a general summary of results and presents some considerations about future research.