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.

Partnership and organizing:an empirical assessment of two contrasting approaches to union revitalization in the UK

The Trades Union Congress (TUC) in Britain has been advocating two contrasting approaches to union revitalization namely: ‘labour—management partnership’ and ‘union organizing’. Using a case study of a public services union this article examines empirically the prospects of union revival offered by these two contrasting approaches. Public services with relatively high union density should offer better prospects for union revival through partnership. However, the authors’ findings indicate that even in public services, partnership was not associated with management’s support for union recruitment, better facility time provisions for union representatives, lower worker grievances or union membership gains. Rank-and-file organizing, on the other hand, was associated with lower worker grievances, greater worker satisfaction with the union, higher worker involvement in union activities and union membership gains. Overall, the findings question the ‘mutual gains’ assertions of partnership advocates and lend support to the critics of partnership who propose an alternative organizing approach to union revitalization.

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.

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.

Discursive approaches to language policy

This book brings together the fields of language policy and discourse studies from a multidisciplinary theoretical, methodological and empirical perspective. The chapters in this volume are written by international scholars active in the field of language policy and planning and discourse studies. The diverse research contexts range from education in Paraguay and Luxembourg via businesses in Wales to regional English language policies in Tajikistan. Readers are thereby invited to think critically about the mutual relationship between language policy and discourse in a range of social, political, economic and cultural spheres. Using approaches that draw on discourse-analytic, anthropological, ethnographic and critical sociolinguistic frameworks, the contributors in this collection explore and refine the ‘discursive’ and the ‘critical’ aspects of language policy as a multilayered, fluid, ideological, discursive and social process that can operate as a tool of social change as well as reinforcing established power structures and inequalities.

Introduction : why are discursive approaches to language policy necessary?

This volume is a series of explorations of language policy from a discursive perspective. Its chief aim is to systematically explore the interconnectedness of language policy and discourse through what we are terming ‘discursive approaches to language policy’ (DALP). We show that language policy is a multilayered phenomenon that is constituted and enacted in and through discourse (which is defined more closely in Sect. 1.2). Language policy is a fast-growing, vibrant, and interdisciplinary field of inquiry that offers a variety of theoretical frameworks, methodologies, analytic approaches, and empirical findings: the framing sections at the beginning of each part of this volume and the commentary at the end frame the discussion of developments in language policy and especially the role of DALP therein.