A novel and rational approach towards designing aluminium chelators

Aluminium (Al) is known to be neurotoxic and has been associated with the aetiology of Alzheimer's Disease. To date, only desferrioxamine (DFO), a trihydroxamic acid siderophore has been used in the clinical environment for the removal of Al from the body. However, this drug is expensive, orally inactive and is associated with many side effects. These studies employed a theoretical approach, with the use of quantum mechanics (QM) via semi-empirical molecular orbital (MO) calculations, and a practical approach using U87-MG glioblastoma cells as a model for evaluating the influence of potential chelators on the passage of aluminium into cells. Preliminary studies involving the Cambridge Structural Database (CSD) identified that Al prefers binding to bidentate ligands in a 3:1 manner, whereby oxygen was the exclusive donating atom. Statistically significant differences in M-O bond lengths when compared to other trivalent metal ions such as Fe3+ were established and used as an acceptance criterion for subsequent MO calculations. Of the semi-empirical methods parameterised for Al, the PM3 Hamiltonian was found to give the most reliable final optimised geometries of simple 3:1 Al complexes. Consequently the PM3 Hamiltonian was used for evaluating the Hf of 3:1 complexes with more complicated ligands. No correlation exists between published stability constants and individual parameters calculated via PM3 optimisations, although investigation of the dicarboxylates reveals a correlation of 0.961 showing promise for affinity prediction of closely related ligands. A simple and inexpensive morin spectrofluorescence assay has been developed and optimised producing results comparable to atomic absorption spectroscopy methods for the quantitative analysis of Al. This assay was used in subsequent in vitro models, initially on E. coli, which indicated that Al inhibits the antimicrobial action of ciprofloxacin, a potent quinolone antibiotic. Ensuing studies using the second model, U87-MG cells, investigated the influence of chelators on the transmembrane transport of Al, identifying 1,2-diethylhydroxypyridin-4-one as a ligand showing greatest potential for chelating Al in the clinical situation. In conclusion, these studies have explored semi-empirical MO Hamiltonians and an in-vitro U87-MG cell line, both as possible methods for predicting effective chelators of Al.

CSR and the "underserving":a role for the state, civil society and business?

Purpose – The purpose of this paper is to demonstrate how the conceptual lens of corporate social responsibility (CSR), business and civil society can be used to explore “less popular causes” (in this case, a community-based public sector empirical study of initiatives with offenders) and, in particular, respond to the question used by Walzer “In which society can lives be best led?” Design/methodology/approach – This is a formative and summative evaluation study of a National Offender Management “community payback” offender scheme based in the UK using a mixed method, predominantly qualitative approach that integrates theory and practice. Findings – The paper finds that citizenship actions of front-line public sector employees, working in partnership with other agencies in the community, embody the essence of Walzer's notion of CSR and civil society by going beyond the call of duty to provide additional training and moral support for the community offenders. Originality/value – The paper contributes towards an understanding of how CSR and civil society debates can inform wider aspects of public policy and business through its application to areas of society that are perceived to be “challenging” and “undeserving”.

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.

Feminist Post-structuralist discourse analysis: a new theoretical and methodological approach?

This chapter serves three very important functions within this collection. First, it aims to make the existence of FPDA better known to both gender and language researchers and to the wider community of discourse analysts, by outlining FPDA’s own theoretical and methodological approaches. This involves locating and positioning FPDA in relation, yet in contradistinction to, the fields of discourse analysis to which it is most often compared: Critical Discourse Analysis (CDA) and, to a lesser extent, Conversation Analysis (CA). Secondly, the chapter serves a vital symbolic function. It aims to contest the authority of the more established theoretical and methodological approaches represented in this collection, which currently dominate the field of discourse analysis. FPDA considers that an established field like gender and language study will only thrive and develop if it is receptive to new ways of thinking, divergent methods of study, and approaches that question and contest received wisdoms or established methods. Thirdly, the chapter aims to introduce some new, experimental and ground-breaking FPDA work, including that by Harold Castañeda-Peña and Laurel Kamada (same volume). I indicate the different ways in which a number of young scholars are imaginatively developing the possibilities of an FPDA approach to their specific gender and language projects.

Intellectual alienation in a fragmented society and universe, as illustrated in the work of Wolfgang Koeppen (1906- )

This text is concerned with the intellectual and social alienation experienced by a twentieth century German writer (1906 - ).·the alienation begins in the context of German society, but this context is later globalised. The thesis first discusses the social and· intellectual origins and the salient features of this alienated stance, before proceeding to a detailed analysis of its recurring symptoms and later intensification in each of the author's main works, chronologically surveyed, supported by reference to minor writings. From the novels of the thirties' showing the burgher-artist conflict, and its symbolic dichotomies, the renunciation of traditional German values, and the ambiguous confrontation with new disruptive socio-political forces, we move to the post-war trilogy (1951-54), with its roots in the German social and political experience of the thirties' onwards. The latter, however, is merely a background for the presentation of a much more comprehensive view of the human condition:- a pessimistic vision of the repetitiveness and incorrigibility of this condition, the possibility of the apocalypse, the bankruptcy and ineffectiveness of European religion and culture, the 'absurd' meaninglessness of history, the intellectual artist's position and role(s) in mass-culture and an abstract, technologised mass-society, the central theme of fragmentation - of the structure of reality, society and personality, the artist's relation to this fragmentation, intensified in the twentieth,century. Style and language are consonant with this world-picture. Many of these features recur in the travel-books (1958-61); diachronic as well as synchronic approaches characterise the presentation of various modes of contemporary society in America, Russia, France and other European countries. Important features of intellectual alienation are:- the changelessness of historical motifs (e.g. tyranny, aggression), the conventions of burgher society, both old and new forms, the qualitative depreciation and standardisation of living, industrialisation and technology in complex, vulnerable and concemtrated urban societies, ambiguities of fragmented pluralism. Reference is made .to other travel-writers.

A linguistic and semantic approach to the theory and practice of literary translation

This work explores the relevance of semantic and linguistic description to translation, theory and practice. It is aimed towards a practical model of approach to texts to translate. As literary texts [poetry mainly] are the focus of attention, so are stylistic matters. Note, however, that 'style', and, to some extent, the conclusions of the work, are not limited to so-called literary texts. The study of semantic description reveals that most translation problems do not stem from the cognitive (langue-related), but rather from the contextual (parole-related) aspects of meaning. Thus, any linguistic model that fails to account for the latter is bound to fall short. T.G.G. does, whereas Systemics, concerned with both the 'Iangue' and 'parole' (stylistic and sociolinguistic mainly) aspects of meaning, provides a useful framework of approach to texts to translate. Two essential semantic principles for translation are: that meaning is the property of a language (Firth); and the 'relativity of meaning assignments' (Tymoczko). Both imply that meaning can only be assessed, correctly, in the relevant socio-cultural background. Translation is seen as a restricted creation, and the translator's encroach as a three-dimensional critical one. To encompass the most technical to the most literary text, and account for variations in emphasis in any text, translation theory must be based on typology of function Halliday's ideational, interpersonal and textual, or, Buhler's symbol, signal, symptom, Functions3. Function Coverall and specific] will dictate aims and method, and also provide the critic with criteria to assess translation Faithfulness. Translation can never be reduced to purely objective methods, however. Intuitive procedures intervene, in textual interpretation and analysis, in the choice of equivalents, and in the reception of a translation. Ultimately, translation, theory and practice, may perhaps constitute the touchstone as regards the validity of linguistic and semantic theories.

Strategic sourcing:a combined QFD and AHP approach in manufacturing

Purpose – This paper aims to develop an integrated analytical approach, combining quality function deployment (QFD) and analytic hierarchy process (AHP) approach, to enhance the effectiveness of sourcing decisions. Design/methodology/approach – In the approach, QFD is used to translate the company stakeholder requirements into multiple evaluating factors for supplier selection, which are used to benchmark the suppliers. AHP is used to determine the importance of evaluating factors and preference of each supplier with respect to each selection criterion. Findings – The effectiveness of the proposed approach is demonstrated by applying it to a UK-based automobile manufacturing company. With QFD, the evaluating factors are related to the strategic intent of the company through the involvement of concerned stakeholders. This ensures successful strategic sourcing. The application of AHP ensures consistent supplier performance measurement using benchmarking approach. Research limitations/implications – The proposed integrated approach can be principally adopted in other decision-making scenarios for effective management of the supply chain. Practical implications – The proposed integrated approach can be used as a group-based decision support system for supplier selection, in which all relevant stakeholders are involved to identify various quantitative and qualitative evaluating criteria, and their importance. Originality/value – Various approaches that can deal with multiple and conflicting criteria have been adopted for the supplier selection. However, they fail to consider the impact of business objectives and the requirements of company stakeholders in the identification of evaluating criteria for strategic supplier selection. The proposed integrated approach outranks the conventional approaches to supplier selection and supplier performance measurement because the sourcing strategy and supplier selection are derived from the corporate/business strategy.

Strategic logistics outsourcing: an integrated QFD and AHP approach

Third-party logistics service providers (3PLs) play a vital role in contemporary supply chain management. Evaluation and selection of the right 3PLs depends on a wide range of quantitative and qualitative criteria rather than cost-based factors. Although various multi-criteria decision making approaches have been proposed, they have not considered the impact of business objectives and requirements of company stakeholders on the evaluating criteria. To enable the "voice" of company stakeholders is considered, this paper develops an integrated approach for selecting 3PL strategically. In the approach, multiple evaluating criteria are derived from the requirements of company stakeholders using a series of house of quality (HOQ). The importance of evaluating criteria is prioritized with respect to the degree of achieving the stakeholder requirements using analytic hierarchy process (AHP). Based on the ranked criteria, alternative 3PLs are evaluated and compared with each other using AHP again to make an optimal selection.

The French fifth Republic as an opportunity structure:a neo-institutional and cultural approach to the study of leadership politics

The Gaullist settlement of 1958 reconfigured the political institutions of France, introducing into the republican mainstream a new form of leadership politics. Adapting the literature on political opportunity structure (POS) theory, and using the French left as a case study, can help us understand how political parties, ideology and leadership adapt to political institutions and norms. It also illuminates what the consequences are of such adaptation in the contemporary period, particularly as regards the institutionally bound roles of political 'character', protocol and discourse. The paper appraises the relevance and appropriateness of POS theory to leadership politics in France.

The individual and society in the GDR under Honecker : orthodoxy, dissidence and internal debate.

The thesis offers a comparative interdisciplinary approach to the examination of the intellectual debates about the relationship between individual and society in the GDR under Honecker. It shows that there was not only a continuum of debate between the academic disciplines, but also from the radical critics of the GDR leadership such as Robert Havemann, Rudolf Bahro and Stefan Heym through the social scientists, literary critics and legal theorists working in the academic institutions to theorists close to the GDR leadership. It also shows that the official line and policy of the ruling party itself on the question of the individual and society was not static over the period, but changed in response to internal and external pressures. Over the period 1971 - 1989 greater emphasis was placed by many intellectuals on the individual, his needs and interests. It was increasingly recognised that conflicts could exist between the individual and society in GDR socialism. Whereas the radical critics argued that these conflicts were due to features of GDR society, such as the hierarchical system of labour functions and bureaucracy, and extrapolated from this a general conflict between the political leadership and population, orthodox critics argued that conflicts existed between a specific individual and society and were largely due to external and historical factors. The internal critics also pointed to the social phenomena which were detrimental to the individual's development in the GDR, but they put forward less radical solutions. With the exception of a few radical young writers, all theorists studied in this thesis gave precedence to social interests over individual interests and so did not advocate a return to `individualistic' positions. The continuity of sometimes quite controversial discussions in the GDR academic journals and the flexibility of the official line and policy suggests that it is inappropriate to refer to GDR society under Honecker simply as totalitarian, although it did have some totalitarian features. What the thesis demonstrates is the existence of `Teiloffentlichkeiten' in which critical discussion is conducted even as the official, orthodox line is given out for public consumption in the high-circulation media.

Heritage and innovative learning approaches:an alternative approach to engineering education

Over recent years, the role of engineering in promoting a sustainable society has received much public attention [1] with particular emphasis given to the need to promote the future prosperity and security of society through the recruitment and education of more engineers [2,3]. From an employment perspective, the Leitch Review [4] suggested that ‘generic’ transferable employability skills development should constitute a more substantial part of university education. This paper argues that the global drivers impacting engineering education [5] correlate strongly to those underpinning the Leitch review, therefore the question of how to promote transferable employability skills within the wider engineering curriculum is increasingly relevant. By exploring the use of heritage in the engineering curriculum as a way to promote learning and engage students, a less familiar approach to study is discussed. This approach moves away from stereotypical notions of the use of information technology as representing the pinnacle of innovation in education. Taking the student experience as its starting point, the paper draws upon the findings of an exploratory study critically analysing the pedagogical value of using heritage in engineering education. It discusses a teaching approach in which engineering students are taken out of their ‘comfort zone’ - away from the classroom, laboratory and computer, to a heritage site some 100 miles away from the university. The primary learning objective underpinning this approach is to develop students’ transferable skills by encouraging them to consider how to apply theoretical concepts to a previously unexplored situation. By reflecting upon students’ perceptions of the value of this approach, and by identifying how heritage may be utilised as an innovative learning and teaching approach in engineering education, this paper makes a notable contribution to current pedagogical debates in the discipline.

Engineering the future! Inspiring student engagement through innovative course and programme design:an empirical approach

An analysis of a bespoke learning and teaching approach developed for use in engineering education

Challenges for expatriate managers:an exploration of cross-cultural management, adjustment, and training issues faced by Anglo-American managers in Hong Kong

This field work study furthers understanding about expatriate management, in particular, the nature of cross-cultural management in Hong Kong involving Anglo-American expatriate and Chinese host national managers, the important features of adjustment for expatriates living and working there, and the type of training which will assist them to adjust and to work successfully in this Asian environment. Qualitative and quantitative data on each issue was gathered during in-depth interviews in Hong Kong, using structured interview schedules, with 39 expatriate and 31 host national managers drawn from a cross-section of functional areas and organizations. Despite the adoption of Western technology and the influence of Western business practices, micro-level management in Hong Kong retains a cultural specificity which is consistent with the norms and values of Chinese culture. There are differences in how expatriates and host nationals define their social roles, and Hong Kong's recent colonial history appears to influence cross-cultural interpersonal interactions. The inability of the spouse and/or family to adapt to Hong Kong is identified as a major reason for expatriate assignments to fail, though the causes have less to do with living away from family and friends, than with Hong Kong's highly urbanized environment and the heavy demands of work. Culture shock is not identified as a major problem, but in Hong Kong micro-level social factors require greater adjustment than macro-level societal factors. The adjustment of expatriate managers is facilitated by a strong orientation towards career development and hard work, possession of technical/professional expertise, and a willingness to engage in a process of continuous 'active learning' with respect to the host national society and culture. A four-part model of manager training suitable for Hong Kong is derived from the study data. It consists of a pre-departure briefing, post-arrival cross-cultural training, language training in basic Cantonese and in how to communicate more effectively in English with non-native speakers, and the assignment of a mentor to newly arrived expatriate managers.

Design and development of an agent-based information system for process improvement

To meet changing needs of customers and to survive in the increasingly globalised and competitive environment, it is necessary for companies to equip themselves with intelligent tools, thereby enabling managerial levels to use the tactical decision in a better way. However, the implementation of an intelligent system is always a challenge in Small- and Medium-sized Enterprises (SMEs). Therefore, a new and simple approach with 'process rethinking' ability is proposed to generate ongoing process improvements over time. In this paper, a roadmap of the development of an agent-based information system is described. A case example has also been provided to show how the system can assist non-specialists, for example, managers and engineers to make right decisions for a continual process improvement. Copyright © 2006 Inderscience Enterprises Ltd.

The EU's 'transnational power over' Central Asia:Developing and applying a structurally integrative approach to the study of the EU's power over Central Asia

This thesis challenges the consensual scholarly expectation of low EU impact in Central Asia. In particular, it claims that by focusing predominantly on narrow, micro-level factors, the prevailing theoretical perspectives risk overlooking less obvious aspects of the EU?s power, including structural aspects, and thus tend to underestimate the EU?s leverage in the region. Therefore, the thesis argues that a more structurally integrative and holistic approach is needed to understand the EU?s power in the region. In responding to this need, the thesis introduces a conceptual tool, which it terms „transnational power over? (TNPO). Inspired by debates in IPE, in particular new realist and critical IPE perspectives, and combining these views with insights from neorealist, neo-institutionalist and constructivist approaches to EU external relations, the concept of TNPO is an analytically eclectic notion, which helps to assess the degree to which, in today?s globalised and interdependent world, the EU?s power over third countries derives from its control over a combination of material, institutional and ideational structures, making it difficult for the EU?s partners to resist the EU?s initiatives or to reject its offers. In order to trace and assess the mechanisms of EU impact across these three structures, the thesis constructs a toolbox, which centres on four analytical distinctions: (i) EU-driven versus domestically driven mechanisms, (ii) mechanisms based on rationalist logics of action versus mechanisms following constructivist logics of action, (iii) agent-based versus purely structural mechanisms of TNPO, and (iv) transnational and intergovernmental mechanisms of EU impact. Using qualitative research methodology, the thesis then applies the conceptual model to the case of EU-Central Asia. It finds that the EU?s power over Central Asia effectively derives from its control over a combination of material, institutional and ideational structures, including its position as a leader in trade and investment in the region, its (geo)strategic and security-related capabilities vis-à-vis Central Asia, as well as the relatively dense level of institutionalisation of its relations with the five countries and the positive image of the EU in Central Asia as a more neutral actor.