Peptide length significantly influences in vitro affinity for MHC class II molecules

Class II Major Histocompatibility Complex (MHC) molecules have an open-ended binding groove which can accommodate peptides of varying lengths. Several studies have demonstrated that peptide flanking residues (PFRs) which lie outside the core binding groove can influence peptide binding and T cell recognition. By using data from the AntiJen database we were able to characterise systematically the influence of PFRs on peptide affinity for MHC class II molecules.

Toward prediction of class II mouse major histocompatibility complex peptide binding affinity:in silico bioinformatic evaluation using partial least squares, a robust multivariate statistical technique

The accurate identification of T-cell epitopes remains a principal goal of bioinformatics within immunology. As the immunogenicity of peptide epitopes is dependent on their binding to major histocompatibility complex (MHC) molecules, the prediction of binding affinity is a prerequisite to the reliable prediction of epitopes. The iterative self-consistent (ISC) partial-least-squares (PLS)-based additive method is a recently developed bioinformatic approach for predicting class II peptide−MHC binding affinity. The ISC−PLS method overcomes many of the conceptual difficulties inherent in the prediction of class II peptide−MHC affinity, such as the binding of a mixed population of peptide lengths due to the open-ended class II binding site. The method has applications in both the accurate prediction of class II epitopes and the manipulation of affinity for heteroclitic and competitor peptides. The method is applied here to six class II mouse alleles (I-Ab, I-Ad, I-Ak, I-As, I-Ed, and I-Ek) and included peptides up to 25 amino acids in length. A series of regression equations highlighting the quantitative contributions of individual amino acids at each peptide position was established. The initial model for each allele exhibited only moderate predictivity. Once the set of selected peptide subsequences had converged, the final models exhibited a satisfactory predictive power. Convergence was reached between the 4th and 17th iterations, and the leave-one-out cross-validation statistical terms - q2, SEP, and NC - ranged between 0.732 and 0.925, 0.418 and 0.816, and 1 and 6, respectively. The non-cross-validated statistical terms r2 and SEE ranged between 0.98 and 0.995 and 0.089 and 0.180, respectively. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made freely available online (http://www.jenner.ac.uk/MHCPred).

Dynamic iterative ontology learning

The fundamental failure of current approaches to ontology learning is to view it as single pipeline with one or more specific inputs and a single static output. In this paper, we present a novel approach to ontology learning which takes an iterative view of knowledge acquisition for ontologies. Our approach is founded on three open-ended resources: a set of texts, a set of learning patterns and a set of ontological triples, and the system seeks to maintain these in equilibrium. As events occur which disturb this equilibrium, actions are triggered to re-establish a balance between the resources. We present a gold standard based evaluation of the final output of the system, the intermediate output showing the iterative process and a comparison of performance using different seed input. The results are comparable to existing performance in the literature.

The effects of relocation on Royal Air Force families

This doctoral research project examines the effects that geographical transience has on Royal Air Force families. The methodology employed in this exploratory and qualitative study consisted largely of open-ended interview questions but also included a series of demographic variables. In total, 29 RAF personnel without families, 33 RAF personnel with families, 33 RAF spouses, and 15 RAF children participated in this research (N = 110). All respondents volunteered to take part in the study and were based in the United Kingdom at the time of data collection. The interviews were transcribed and content coded according to six major relocation themes arising from the literature (change, tasks, support, coping, difficulty, and outcome). QSR NVIVO 2.0, a qualitative data analysis software package, was used to facilitate the process. Through the utilisations of qualitative methodology, the researcher was able to offer various novel and reoccurring variables that appear to play an important role (at least subjectively) in relocation. Additionally, frequencies associated with these factors were presented. The findings were integrated with those from the literature in order to offer an initial comparison and differentiation between civilian and military samples. The main theoretical contributions were the introduction of the concept of mobile mentality, the creation of a novel relocation model that takes familial interaction into account, and the development of a taxonomy for the classification of relocation outcomes. Finally, additional observations, recommendations for future research, and practical implications are reviewed.

Time and professional work in public sector organisations: an examination of four occupational groups in education and medicine

The aim of this thesis is to examine the experience of time of four professional occupational groups working in public sector organisations and the factors affecting this experience. The literature on time and work is examined to delineate the key parameters of research in this area. A broad organisation behaviour approach to the experience of time and work is developed in which individual, occupational, organisational and socio-political factors are inter-related. The experience of secondary school teachers, further education lecturers, general medical practitioners and hosoital consultants is then examined. Multiple methods of data collection are used: open-ended interviews, a questionnaire survey and the analysis of key documents relating to the institutional settings in which the four groups work. The research aims to develop our knowledge of working time by considering the dimensions of the experience of time at work, the contexts in wlhich this experience is generated and the constraints these contexts give rIse to. By developing our understanding of time as a key feature of work experience we also extend our knowledge of organisation behaviour in general. In conclusion a model of the factors relating the experience of time to the negotiation of time at work is presented.

Constant shear along a boundary of a flume

'I'he accurate rreasurement of bed shear stress has been extremely difficult due to its changing values until white propunded a theory which would give constant shear along the bed of a flume. In this investigation a flume has been designed according to White's theory and by two separate methods proven to give constant shearing force along the bed. The first method applied the Hydrogen Bubble Technique to obtain accurate values of velocity thus allowing the velocity profile to be plotted and the momentum at the various test sections to be calculated. The use of a 16 mm Beaulieu movie camera allowed the exact velocity profiles created by the hydrogen bubbles to be recorded whilst an analysing projector gave the means of calculating the exact velocities at the various test sections. Simultaneously Preston's technique of measuring skin friction using Pitot tubes was applied. Twc banks of open ended water manometer were used for recording the static and velocity head pressure drop along the flume. This tvpe of manometer eliminated air locks in the tubes and was found to be sufficiently accurate. Readings of pressure and velocity were taken for various types and diameters of bed material both natural sands and glass spheres and the results tabulated. Graphs of particle Reynolds Number against bed shear stress were plotted and gave a linear relationship which dropped off at high values of Reynolds number. It was found that bed movement occurred instantaneously along the bed of the flume once critical velocity had been reached. On completion of this test a roof curve inappropriate to the bed material was used and then the test repeated. The bed shearing stress was now no longer constant and yet bed movement started instantaneously along the bed of the flume, showing that there are more parameters than critical shear stress to bed movement. It is concluded from the two separate methods applied that the bed shear stress is constant along the bed of the flume.

Using the theory of planned behaviour to understand binge drinking:the importance of beliefs for developing interventions

Objectives. To elicit students' salient beliefs in relation to binge drinking, and to examine the extent to which individual salient beliefs predict theory of planned behaviour (TPB) constructs in relation to binge drink, and actual drinking behaviour assessed later that evening. Design. Longitudinal, over a single evening. Methods. 192 students were recruited as they entered a campus bar at the beginning of the evening. They completed questionnaires with open-ended questions eliciting beliefs concerning binge drinking, and ratings scales assessing standard TPB constructs in relation to binge drinking. At the end of the evening, 181 completed a second questionnaire and recorded the number of alcoholic drinks they had consumed. Results. Beliefs were reliably coded (all kappas =0.79). Students with higher intentions to binge drink were more likely to believe that their friends approved of binge drinking, and that (lack of) money would make it difficult. Students who reported drinking more alcohol at the end of the evening were more likely to believe that getting drunk is an advantage/what they would like about binge drinking tonight, that their sports teams would approve, and that celebrating, drinking patterns, and environment would make it easy to binge drink. Conclusions. The present study has identified the individually salient beliefs relating to drinking behaviour that the TPB states should be addressed by interventions to alter behaviour, and which that should be assessed as mediators in intervention research. As a whole, these findings highlight the importance of perceived peer norms in binge drinking in this population, and support the idea of interventions to challenge the perception of social pressure to binge drink. ©2011 The British Psychological Society.

Weakly supervised joint sentiment-topic detection from text

Sentiment analysis or opinion mining aims to use automated tools to detect subjective information such as opinions, attitudes, and feelings expressed in text. This paper proposes a novel probabilistic modeling framework called joint sentiment-topic (JST) model based on latent Dirichlet allocation (LDA), which detects sentiment and topic simultaneously from text. A reparameterized version of the JST model called Reverse-JST, obtained by reversing the sequence of sentiment and topic generation in the modeling process, is also studied. Although JST is equivalent to Reverse-JST without a hierarchical prior, extensive experiments show that when sentiment priors are added, JST performs consistently better than Reverse-JST. Besides, unlike supervised approaches to sentiment classification which often fail to produce satisfactory performance when shifting to other domains, the weakly supervised nature of JST makes it highly portable to other domains. This is verified by the experimental results on data sets from five different domains where the JST model even outperforms existing semi-supervised approaches in some of the data sets despite using no labeled documents. Moreover, the topics and topic sentiment detected by JST are indeed coherent and informative. We hypothesize that the JST model can readily meet the demand of large-scale sentiment analysis from the web in an open-ended fashion.

Nurturing health-related online support groups:exploring the experience of patient moderators

The aim of this study was to examine the views of moderators across a diverse and geographically broad range of online support groups about their moderator experiences and to explore both the personal benefits as well as challenges involved. Thirty-three patient moderators completed an online questionnaire which included a series of open-ended questions. Thematic analysis identified three themes: emergence, empowerment, nurturing. Several moderators declared their own diagnosis and for some, being able to share personal insights motivated them to establish the group and in turn offered validation. They felt empowered by helping others and learned more about the condition through accessing the "communal brain". Some felt the group aided patients' access to health services and their ability to communicate with health professionals while others worried about them becoming over-dependent. Moderators described needing to nurture their group to ensure it offered a safe space for members. Clear rules of engagement, trust, organisation skills, compassion and kindness were considered essential. Patient moderated online support groups can be successfully developed and facilitated and can be empowering for both the group member and moderator alike.© 2013 Elsevier Ltd. All rights reserved.

Using cognitive load theory to interpret student difficulties with a problem-based learning approach to engineering education:a case study

This article reports on an investigationwith first year undergraduate ProductDesign and Management students within a School of Engineering and Applied Science. The students at the time of this investigation had studied fundamental engineering science and mathematics for one semester. The students were given an open ended, ill-formed problem which involved designing a simple bridge to cross a river.They were given a talk on problemsolving and given a rubric to follow, if they chose to do so.They were not given any formulae or procedures needed in order to resolve the problem. In theory, they possessed the knowledge to ask the right questions in order tomake assumptions but, in practice, it turned out they were unable to link their a priori knowledge to resolve this problem. They were able to solve simple beam problems when given closed questions. The results show they were unable to visualize a simple bridge as an augmented beam problem and ask pertinent questions and hence formulate appropriate assumptions in order to offer resolutions.

The process of coping in King-Kopetzky Syndrome

Our object was to describe the process of coping in King-Kopetzky syndrome and hypothesise how the process is mediated. We used a qualitative study using open-ended interviews. The data were gathered purposefully from 19 cases in the first phase of the study. Accounts were then compared deductively with six accounts from a previous interview-based study. Maximum contrast was sought in cases and in experience of clinical interventions. Participants were recruited from Hearing Therapy services in Bath and North East Somerset Primary Care Trust and The Welsh Hearing Institute. Interviews were conducted in participants’ homes or clinic setting. Coping was determined by the concept that the individual developed about their hearing difficulties. The process of conceptualizing involves reconciling the symptoms experienced with the information obtained from clinicians. The process is mediated by the context in which hearing difficulties occur and the interventions that are received. Forming a coherent concept of hearing difficulties facilitates coping. Clinicians can assist this process by giving patients with King-Kopetzky Syndrome an explanation of the condition.

The Kim Dynasty and North-East Asian security:breaking the cycle of crises?

Purpose—This article considers North Korea and the notion of crisis, by linking historical development over the Korean peninsula to the conflict resolution literature, and investigates why despite a large number of destabilizing events, a war involving Pyongyang has yet to erupt. Design/methodology—This article uses historical data and a framework developed by Aggarwal et al., in order to highlight patterns of interaction between states such as the United States, North Korea and South Korea, organizations such as the United Nations, as well as processes such as the Six- Party Talks and the Agreed Framework. The article then develops a crisis framework based on conflict resolution and negotiation literature, and applies it to three North Korean administrations. Findings—Findings suggest that an open- ended understanding of time (for all parties involved on the peninsula) leads to an impossibility to reach a threshold where full- scale war would be triggered, thus leaving parties in a stable state of crisis for which escalating moves and de- escalating techniques might become irrelevant. Practical implications—It is hoped that this article will help further endeavors linking conflict resolution theoretical frameworks to the Korean peninsula security situation. In the case of the Korean peninsula, time has been understood as open-ended, leading parties to a lingering state of heightened hostilities that oscillates toward war, but that is controlled enough not to reach it. In-depth analysis of particular security sectors such as nuclear energy, food security, or missile testing would prove particularly useful in understanding the complexity of the Korean peninsula situation to a greater extent. It is hoped that this paper will help further endeavours linking conflict resolution theoretical frameworks to the Korean peninsula security situation. Originality/value—This research suggests that regarding the Korean peninsula, time has been understood as open- ended, leading parties to a lingering state of heightened.

How does problem based learning fit with cognitive load theory?

This paper reports on an investigation with first year undergraduate Product Design and Management students within a School of Engineering. The students at the time of this investigation had studied fundamental engineering science and mathematics for one semester. The students were given an open ended, ill formed problem which involved designing a simple bridge to cross a river. They were given a talk on problem solving and given a rubric to follow, if they chose to do so. They were not given any formulae or procedures needed in order to resolve the problem. In theory, they possessed the knowledge to ask the right questions in order to make assumptions but, in practice, it turned out they were unable to link their a priori knowledge to resolve this problem. They were able to solve simple beam problems when given closed questions. The results show they were unable to visualise a simple bridge as an augmented beam problem and ask pertinent questions and hence formulate appropriate assumptions in order to offer resolutions.

Book review: Laurel Kamada, Hybrid Identities and Adolescent Girls: Being Half in Japan. Bristol: Multilingual Matters, 2010

Arguably, the catalyst for the best research studies using social analysis of discourse is personal ‘lived’ experience. This is certainly the case for Kamada, who, as a white American woman with a Japanese spouse, had to deal first hand with the racialization of her son. Like many other mixed-ethnic parents, she experienced the shock and disap-pointment of finding her child being racialized as ‘Chinese’ in America through peer group taunts, and constituted as gaijin (a foreigner) in his own homeland of Japan. As a member of an e-list of the (Japan) Bilingualism Special Interest Group (BSIG), Kamada learnt that other parents from the English-speaking foreign community in Japan had similar disturbing stories to tell of their mixed-ethnic children who, upon entering the Japanese school system, were mocked, bullied and marginalized by their peers. She men-tions a pervasive Japanese proverb which warns of diversity or difference getting squashed: ‘The nail that sticks up gets hammered down’. This imperative to conform to Japanese behavioural and discursive norms prompted Kamada’s quest to investigate the impact of ‘otherization’ on the identities of children of mixed parentage. In this fascinat-ing book, she shows that this pressure to conform is balanced by a corresponding cele-bration of ‘hybrid’ or mixed identities. The children in her study are also able to negotiate their identities positively as they come to terms with contradictory discursive notions of ‘Japaneseness’, ‘whiteness’ and ‘halfness/doubleness’.The discursive construction of identity has become a central concern amongst researchers across a wide range of academic disciplines within the humanities and the social sciences, and most existing work either concentrates on a specific identity cate-gory, such as gender, sexuality or national identity, or else offers a broader discussion of how identity is theorized. Kamada’s book is refreshing because it crosses the usual boundaries and offers divergent insights on identity in a number of ways. First, using the term ‘ethno-gendering’, she examines the ways in which six mixed-ethnic girls living in Japan accomplish and manage the relationship between their gender and ethnic ‘differ-ences’ from age 12 to 15. She analyses in close detail how their actions or displays within certain situated interactions might come into conflict with how they are seen or constituted by others. Second, Kamada’s study builds on contemporary writing on the benefits of hybridity where identities are fluid, flexible and indeterminate, and which contest the usual monolithic distinctions of gender, ethnicity, class, etc. Here, Kamada carves out an original space for her findings. While scholars have often investigated changing identities and language practices of young people who have been geographi-cally displaced and are newcomers to the local language, Kamada’s participants were all born and brought up in Japan, were fluent in Japanese and were relatively proficient in English. Third, the author refuses to conceptualize or theorize identity from a single given viewpoint in preference to others, but in postmodernist spirit draws upon multiple perspectives and frameworks of discourse analysis in order to create different forms of knowledge and understandings of her subject. Drawing on this ‘multi-perspectival’ approach, Kamada examines grammatical, lexical, rhetorical and interactional features from six extensive conversations, to show how her participants position their diverse identities in relation to their friends, to the researcher and to the outside world. Kamada’s study is driven by three clear aims. The first is to find out ‘whether there are any tensions and dilemmas in the ways adolescent girls of Japanese and “white” mixed parentage in Japan identify themselves in terms of ethnicity’. In Chapter 4, she shows how the girls indeed felt that they stood out as different and consequently experienced isolation, marginalization and bullying at school – although they were able to make better sense of this as they grew older, repositioning the bullies as pitiable. The second aim is to ask how, if at all, her participants celebrate their ethnicity, and furthermore, what kind of symbolic, linguistic and social capital they were able to claim for themselves on the basis of their hybrid identities. In Chapter 5, Kamada shows how the girls over time were able to constitute themselves as insiders while constituting ‘the Japanese’ as outsiders, and their network of mixed-ethnic friends was a key means to achieve this. In Chapter 6, the author develops this potential celebration of the girls’ mixed ethnicity by investigating the privileges they perceived it afforded them – for example, having the advantage of pos-sessing English proficiency and intercultural ‘savvy’ in a globalized world. Kamada’s third aim is to ask how her participants positioned themselves and performed their hybrid identities on the basis of their constituted appearance: that is, how the girls saw them-selves based on how they looked to others. In Chapter 7, the author shows that, while there are competing discourses at work, the girls are able to take up empowering positions within a discourse of ‘foreigner attractiveness’ or ‘a white-Western female beauty’ discourse, which provides them with a certain cachet among their Japanese peers. Throughout the book, Kamada adopts a highly self-reflexive perspective of her own position as author. For example, she interrogates the fact that she may have changed the lived reality of her six participants during the course of her research study. As the six girls, who were ‘best friends’, lived in different parts of the Morita region of Japan, she had to be proactive in organizing six separate ‘get-togethers’ through the course of her three-year study. She acknowledges that she did not collect ‘naturally occurring data’ but rather co-constructed opportunities for the girls to meet and talk on a regular basis. At these meetings, she encouraged the girls to discuss matters of identity, prompted by open-ended interview questions, by stimulus materials such as photos, articles and pic-tures, and by individual tasks such as drawing self-portraits. By giving her participants a platform in this way, Kamada not only elicited some very rich spoken data but also ‘helped in some way to shape the attitudes and self-images of the girls positively, in ways that might not have developed had these get-togethers not occurred’ (p. 221). While the data she gathers are indeed rich, it may well be asked whether there is a mismatch between the girls’ frank and engaging accounts of personal experience, and the social constructionist academic register in which these are later re-articulated. When Kamada writes, ‘Rina related how within the more narrow range of discourses that she had to draw on in her past, she was disempowered and marginalized’ (p. 118), we know that Rina’s actual words were very different. Would she really recognize, understand and agree with the reported speech of the researcher? This small omission of self-reflexivity apart – an omission which is true of most lin-guistic ethnography conducted today – Kamada has written a unique, engaging and thought-provoking book which offers a model to future discourse analysts investigating hybrid identities. The idea that speakers can draw upon competing discourses or reper-toires to constitute their identities in contrasting, creative and positive ways provides linguistic researchers with a clear orientation by which to analyse the contradictions of identity construction as they occur across time in different discursive contexts