Computational modelling approaches to vaccinology

Excepting the Peripheral and Central Nervous Systems, the Immune System is the most complex of somatic systems in higher animals. This complexity manifests itself at many levels from the molecular to that of the whole organism. Much insight into this confounding complexity can be gained through computational simulation. Such simulations range in application from epitope prediction through to the modelling of vaccination strategies. In this review, we evaluate selectively various key applications relevant to computational vaccinology: these include technique that operates at different scale that is, from molecular to organisms and even to population level.

New approaches to North Korean politics after reunification:the search for a common Korean identity

Whilst most of the literature focusing on the Korean peninsula has concentrated on how to achieve unification through confidence-building measures, dialogues, negotiation and diplomacy, little attention has been paid to how a unified Korean identity, a core component of any potential reunification scheme could develop and be sustained. The paper addresses this gap by: (1) defining what national identity is, and how Korean identities have been formed, (2) outlining how both South and North Korea have understood and used the concept of national identity, (3) suggesting possible grounds on which the two Koreas could build a new, common national identity. © 2014 The Regents of the University of California.

Truly interactive approaches to browsing image databases

Image collections are ever growing and hence efficient and effective tools to manage these repositories are highly sought after. In this paper, we present effective image browsing systems that are operated on a large multi-touch environment for truly interactive exploration. Not only do image browsers pose a useful alternative to retrieval-based systems, they also provide a visualisation of the whole image collection and allow users to interactively explore particular parts of the collection. Our systems are based on the idea that visually similar images are located close to each other in the visualisation, that image thumbnails are arranged on a regular lattice (either a regular grid projected onto a sphere or a hexagonal lattice), and that large image datasets can be accessed through a hierarchical tree structure. A pilot study has shown that the presented systems do indeed work well and are preferred compared to conventional image browsers. © 2011 IEEE.

Attitudes to language in literary sources:beyond post-colonialism in nigerian literature

All societies display attitudes to (varieties of) languages that tell us about the relative status of the groups that are associated to them. One method to document these is the systematic study of public discourses, including literary production. How (varieties of) languages are used, mentioned and characterised in a literary work tells us about their social status, and any change in this status should therefore be followed by changes in judgements on languages. This is demonstrated by the present paper with reference to the language attitudes in Nigeria, on the basis of two iconic Nigerian novels 2004 Purple Hibiscus and in 1958 classic postcolonial Things Fall Apart, separated by nearly fifty years. Ibo as well as Pidgin, Nigerian and European Englishes are presented in Purple Hibiscus in nuanced complementary configurations. A strong axiological polarisation is by contrast offered in Things Fall Apart between Ibo speakers and Ibo interpreters who are presented as cruel and ridiculous traitors siding with the English colonising power whose language, curiously, is not commented upon. Showing how a replicable method applied to language judgements can document social organisation and change, these results validate the view that the Nigerian society and culture has moved beyond the historically situated postcolonialist movement to embrace a globalised paradigm. © 2010 Taylor & Francis.

The redoxomics of PTEN: walking a fine line between damage and signaling:mass spectrometry-based approaches to study the effect of oxidation on PTEN function, structure, and protein-protein interactions

The research described in this PhD thesis focuses on proteomics approaches to study the effect of oxidation on the modification status and protein-protein interactions of PTEN, a redox-sensitive phosphatase involved in a number of cellular processes including metabolism, apoptosis, cell proliferation, and survival. While direct evidence of a redox regulation of PTEN and its downstream signaling has been reported, the effect of cellular oxidative stress or direct PTEN oxidation on PTEN structure and interactome is still poorly defined. In a first study, GST-tagged PTEN was directly oxidized over a range of hypochlorous acid (HOCl) concentration, assayed for phosphatase activity, and oxidative post-translational modifications (oxPTMs) were quantified using LC-MS/MS-based label-free methods. In a second study, GSTtagged PTEN was prepared in a reduced and reversibly H2O2-oxidized form, immobilized on a resin support and incubated with HCT116 cell lysate to capture PTEN interacting proteins, which were analyzed by LC-MS/MS and comparatively quantified using label-free methods. In parallel experiments, HCT116 cells transfected with a GFP-tagged PTEN were treated with H2O2 and PTENinteracting proteins immunoprecipitated using standard methods. Several high abundance HOCl-induced oxPTMs were mapped, including those taking place at amino acids known to be important for PTEN phosphatase activity and protein-protein interactions, such as Met35, Tyr155, Tyr240 and Tyr315. A PTEN redox interactome was also characterized, which identified a number of PTEN-interacting proteins that vary with the reversible inactivation of PTEN caused by H2O2 oxidation. These included new PTEN interactors as well as the redox proteins peroxiredoxin-1 (Prdx1) and thioredoxin (Trx), which are known to be involved in the recycling of PTEN active site following H2O2-induced reversible inactivation. The results suggest that the oxidative modification of PTEN causes functional alterations in PTEN structure and interactome, with fundamental implications for the PTEN signaling role in many cellular processes, such as those involved in the pathophysiology of disease and ageing.

Brain oscillations and connectivity in autism spectrum disorders (ASD):new approaches to methodology, measurement and modelling

Although atypical social behaviour remains a key characterisation of ASD, the presence ofsensory and perceptual abnormalities has been given a more central role in recentclassification changes. An understanding of the origins of such aberrations could thus prove afruitful focus for ASD research. Early neurocognitive models of ASD suggested that thestudy of high frequency activity in the brain as a measure of cortical connectivity mightprovide the key to understanding the neural correlates of sensory and perceptual deviations inASD. As our review shows, the findings from subsequent research have been inconsistent,with a lack of agreement about the nature of any high frequency disturbances in ASD brains.Based on the application of new techniques using more sophisticated measures of brainsynchronisation, direction of information flow, and invoking the coupling between high andlow frequency bands, we propose a framework which could reconcile apparently conflictingfindings in this area and would be consistent both with emerging neurocognitive models ofautism and with the heterogeneity of the condition.

Language policy and critical discourse studies:towards an integrated approach

This chapter offers a framework for combining critical language policy with critical discourse studies (CDS) to analyse language policy as a process in the context of minority language policy in Wales. I propose a discursive approach to language policy, which starts from the premise that language policy is constituted, enacted, interpreted and (re)contextualised in and through language. This approach extends the critical language policy framework provided by Shohamy (Language policy: hidden agendas and new approaches. Routledge, London, 2006) and integrates perspectives from the context-sensitive discourse-historical approach in CDS. It incorporates discourse as an essential lens through which policy mechanisms, ideologies and practices are constituted and de facto language policy materialises. This chapter argues that conceptualising and analysing language policy as a discursive phenomenon enables a better understanding of the multi-layered nature of language policy that shapes the management and experience of corporate bilingualism in Wales.

To cut a long story short:an analysis of formulaic sequences in short written narratives and their potential as markers of authorship

Previous research into formulaic language has focussed on specialised groups of people (e.g. L1 acquisition by infants and adult L2 acquisition) with ordinary adult native speakers of English receiving less attention. Additionally, whilst some features of formulaic language have been used as evidence of authorship (e.g. the Unabomber’s use of you can’t eat your cake and have it too) there has been no systematic investigation into this as a potential marker of authorship. This thesis reports the first full-scale study into the use of formulaic sequences by individual authors. The theory of formulaic language hypothesises that formulaic sequences contained in the mental lexicon are shaped by experience combined with what each individual has found to be communicatively effective. Each author’s repertoire of formulaic sequences should therefore differ. To test this assertion, three automated approaches to the identification of formulaic sequences are tested on a specially constructed corpus containing 100 short narratives. The first approach explores a limited subset of formulaic sequences using recurrence across a series of texts as the criterion for identification. The second approach focuses on a word which frequently occurs as part of formulaic sequences and also investigates alternative non-formulaic realisations of the same semantic content. Finally, a reference list approach is used. Whilst claiming authority for any reference list can be difficult, the proposed method utilises internet examples derived from lists prepared by others, a procedure which, it is argued, is akin to asking large groups of judges to reach consensus about what is formulaic. The empirical evidence supports the notion that formulaic sequences have potential as a marker of authorship since in some cases a Questioned Document was correctly attributed. Although this marker of authorship is not universally applicable, it does promise to become a viable new tool in the forensic linguist’s tool-kit.

Bringing engineering education to life:an empirical approach

This paper focuses upon the argument that the role played by the engineering profession within today's society has changed markedly over the past several years from providing the foundations for contemporary life to leading societal change and becoming one of the key driver's of future social development. Coining the term 'Engineering-Sociology' this paper contributes to engineering education and engineering education research by proposing a new paradigm upon which future engineering education programmes and engineering education research might build. Developed out of an approach to learning and teaching practice, Engineering-Sociology encapsulates both traditional and applied approaches to engineering education and engineering education research. It suggests that in order to meet future challenges there is a need to bring together what are generally perceived to be two diametrically opposed paradigms, namely engineering and sociology. Building on contemporary theoretical and pedagogical arguments in engineering education research, the paper concludes that by encouraging engineering educators to 'think differently', Engineering-Sociology can provide an approach to learning and teaching that both enhances the student experience and meets the changing needs of society.

Le paradoxe de l'interprétation:À propos du calcul du sens de certains indéfinis

The meaning is involved all levels of language analysis. Located in the heart of phenomena such as the polysemy, the grammaticalisation, the role for interpretation of the syntax, the organisation of the metonymy, the structuring of the metaphor. It is subject to synchroniques and historical typological and social variations. These events allow you to reveal when they are considered under the representations that they involve, the Organization of the linguistic meaning report. It is this organisation that attach themselves to identify the contributions in this book. From the empirical study of problems typical semantics and prag-matique offer answers provide the most current approaches to questions the nature of the sense of the patterns they render account representations and constraints that shape.

From national innovation systems to national innovation capacity:internationalisation and technology transfer perspectives

The last decade or so has witnessed the emergence of the national innovation system (NIS) phenomenon. Since then, many scholars have investigated NIS and its implementation in different countries. However, there are very few investigations into the relationship between the NIS of a country and its national innovation capacity. This paper aims to make a contribution in this area by examining the link that currently exists between these two topics. Whilst examining this relationship, we also explore internationalisation and technology transfer, being cognate areas that have been investigated during the same period. This follows our assertion that the link between NIS and national innovation capacity is the mechanism of internationalisation and technology transfer. The NIS approach was introduced in the late 1980s (see Freeman, 1987; Dosi et al., 1988) and further elaborated later (see Lundvall, 1992; Nelson, 1993; Edquist, 1997). In essence, a country?s NIS is a historically grown subsystem of the entire national economy consisting of organisations and institutions which play a major role in the innovative activity in the country. In the NIS approach, interactions within organisations as well as the interplay between organisations and institutions are of central importance. The NIS approach has been used to reveal the structure of the innovation processes and the main actors involved in them in industrialised and emerging countries. Although the national focus remains strong, it has been accompanied by studies seeking to analyse the notion of systems of innovation at an international level and at a sub-national scale (Archibugi et al., 1999). Dosi in the edition of Archibugi et al. (1999) argues that the general background of the discussion of national systems is the observation of non-random distributions across countries of: corporate capabilities; organisational forms; strategies; and ultimately revealed performances, in terms of production efficiency and inputs productivities, rates of innovation, rates of adoption/diffusion of innovation themselves, dynamics of market shares on the world markets, growth of income and employment. They also mention that there are several approaches to NIS. Nelson (1993) focuses upon the specificities of national institutions and policies supporting directly or indirectly innovation, diffusion and skills accumulation. Patel and Pavitt (1991) have stressed the links between the national patterns of technological accumulation and the competencies and innovative strategies of a few major national companies. Amable et al (1997) and Soskice (1993) and Zysman (1994) focus on the specifics of national institutions including, for example, the forms of organization, financial and labour markets, training institutions, forms of state intervention in the economy etc. However, the most common reference is by Lundvall (1992) who argues that the focus on the national level is associated with the fact that national economies vary according to their production system and their institutional framework and these differences are in turn strengthened by different historical experiences, language and culture. On the other hand, the national innovation capability consists of abilities to create and carry new technological possibilities through to economic practice. The term covers a wide range of activities from capability to invent to capability to innovate and to capability to improve existing technology beyond the original design parameters (Kim, 1997). The term innovation is often associated by many with technological change at international frontiers. However, technological capability is not the same as innovation capability. Technological capability refers to assimilation, use, adaptation, and change to existing technologies. It also enables the creation of new technologies and development of new products and processes in response to changing economic environments. It denotes operational command over knowledge (Kim, 1997). It is manifested not merely by the knowledge possessed, but, more important, by the uses to which that knowledge can be put and by the proficiency with which it is applied in the activities of investment and production and in the creation of new knowledge (Westphal et al., 1985). Therefore, the analytical framework that is used in this paper is based on the way a country derives from its NIS a national innovation capacity. There are two perspectives that are identified on this way. These are internationalisation and technology transfer. Even though NIS is not directly related to national innovation capacity, to achieve national innovation capacity from NIS, the country should have the ability for technology transfer. Technology transfer is a link between these two phenomena. On the other hand, internationalisation can be either the input or the output of the relationship between NIS and national innovation capability. If a company is investing in a country because of its national innovation capacity, this can be regarded as an input to the relationship between NIS and national innovation capacity. If this company is investigating the national innovation capacity of a country then, for its internationalisation, the national innovation capacity should be important, which in turn means this company is active in innovation and innovation is also an important success factor. The interrelationship between the investment of the company and the NIS of the country (assuming that the country is competent and competitive in technology transfer) will generate and improve that country?s national innovation capacity. This is the output of internationalisation from the relationship between NIS and national innovation capacity. When companies are evaluating whether to internationalise, they investigate certain factors in the countries in which they are considering to invest. The ability to transfer technology is dependent on ability to adopt a new technology and also on the learning derived from this technology. If countries wish to attract innovation related investment they need to show their ability to have a NIS and also the capability to transfer technology. Without the technology transfer capability, the NIS is not functioning. Therefore, companies that internationalise will investigate the factors common to NIS, technology transfer, and their business needs. Through this paper we will demonstrate this link though its mechanisms. Our research will be through extensive literature review and identifying relevant aspects of previous research carried out by the authors. It will investigate certain factors of different countries that are successful in attracting innovation related foreign direct investment. Through these, we will point out the factors that are important for the link and mechanisms of NIS and national innovation capability.

Reconstructing the past? Low German and the creating of regional identity in public language display

This article deals with language contact between a dominant standard language -German - and a lesser-used variety - Low German - in a situation in which the minoritised language is threatened by language shift and language loss. It analyses the application of Low German in forms of public language display and the selfpresentation of the community in tourism brochures, focusing on bilingual linguistic practices on the one hand and on underlying discourses on the other. It reveals that top-down and bottom-up approaches to implementing Low German in public language display show a remarkable homogeneity, thus creating a regional 'brand'. The article asks whether a raised level of visibility will in itself guarantee better chances for linguistic maintenance and survival of the threatened language. © 2011 Taylor & Francis.

Moving from HRM to knowledge productivity:a study of whether and how organizations become learning organizations

Practitioners and academics are in broad agreement that, above all, organizations need to be able to learn, to innovate and to question existing ways of working. This thesis develops a model to take into account, firstly, what determines whether or not organizations endorse practices designed to facilitate learning. Secondly, the model evaluates the impact of such practices upon organizational outcomes, measured in terms of products and technological innovation. Researchers have noted that organizations that are committed to producing innovation show great resilience in dealing with adverse business conditions (e.g. Pavitt, 1991; Leonard Barton, 1998). In effect, such organizations bear many of the characteristics associated with the achievement of ‘learning organization’ status (Garvin, 1993; Pedler, Burgoyne & Boydell, 1999; Senge, 1990). Seven studies are presented to support this theoretical framework. The first empirical study explores the antecedents to effective learning. The three following studies present data to suggest that people management practices are highly significant in determining whether or not organizations are able to produce sustained innovation. The thesis goes on to explore the relationship between organizational-level job satisfaction, learning and innovation, and provides evidence to suggest that there is a strong, positive relationship between these variables. The final two chapters analyze learning and innovation within two similar manufacturing organizations. One manifests relatively low levels of innovation whilst the other is generally considered to be outstandingly innovative. I present the comparative framework for exploring the different approaches to learning manifested by the two organizations. The thesis concludes by assessing the extent to which the theoretical model presented in the second chapter is borne out by the findings of the study. Whilst this is a relatively new field of inquiry, findings reveal that organizations have a much stronger chance of producing sustained innovation where they manage people proactively where people process themselves to be satisfied at work. Few studies to date have presented empirical evidence to substantiate theoretical endorsements to engage in higher order learning, so this research makes an important contribution to existing literature in this field.

The impact of the language barrier on the management of multinational companies : a case study and survey, based exploration of the impact of the language barrier on the strategies, policies and systems by which multinational companies manage their subsidaries

The thesis begins with a conceptual model of the way that language diversity affects the strategies, organisation and subsidiary control policies of multinational companies. The model is based solely on the researcher'’ personal experience of working in a variety of international management roles, but in Chapter 2 a wide-ranging review of related academic literature finds evidence to support the key ideas. The model is developed as a series of propositions which are tested in a comparative case study, refined and then re-tested in a global survey of multinational subsidiaries. The principal findings of the empirical phases of the thesis endorse the main tenets of the model: - That language difference between parent and subsidiary will impair communication, create mistrust and impede relationship development. - That subsequently the feelings of uncertainty, suspicion and mistrust will influence the decisions taken by the parent company. - They will have heightened sensitivity to language issues and will implement policies to manage language differences. - They will adopt low-risk strategies in host countries where they are concerned about language difference. - They will use organisational and manpower strategies to minimise the consequences and risks of the communications problems with the subsidiary. - As a consequence the level of integration and knowledge flow between parent and subsidiary will be curtailed. - They will adopt styles of control that depend least on their ability to communicate with their subsidiary. Although there is adequate support for all of the above conclusions, on some key points the evidence of the Case Studies and Survey is contradictory. The thesis, therefore, closes with an agenda for further research that would address these inconsistencies.

Doing action research in English language teaching:a guide for practitioners

This hands-on, practical guide for ESL/EFL teachers and teacher educators outlines, for those who are new to doing action research, what it is and how it works. Straightforward and reader friendly, it introduces the concepts and offers a step-by-step guide to going through an action research process, including illustrations drawn widely from international contexts. Specifically, the text addresses: •action research and how it differs from other forms of research •the steps involved in developing an action research project •ways of developing a research focus •methods of data collection •approaches to data analysis •making sense of action research for further classroom action. Each chapter includes a variety of pedagogical activities: •Pre-Reading questions ask readers to consider what they already know about the topic •Reflection Points invite readers to think about/discuss what they have read •action points ask readers to carry out action-research tasks based on what they have read •Classroom Voices illustrate aspects of action research from teachers internationally •Summary Points provide a synopsis of the main points in the chapter