Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. 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 are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

Marking high-technology market evolution through the foci of market stories:the case of local area networks

Previous research suggests that changing consumer and producer knowledge structures play a role in market evolution and that the sociocognitive processes of product markets are revealed in the sensemaking stories of market actors that are rebroadcasted in commercial publications. In this article, the authors lend further support to the story-based nature of market sensemaking and the use of the sociocognitive approach in explaining the evolution of high-technology markets. They examine the content (i.e., subject matter or topic) and volume (i.e., the number) of market stories and the extent to which content and volume of market stories evolve as a technology emerges. Data were obtained from a content analysis of 10,412 article abstracts, published in key trade journals, pertaining to Local Area Network (LAN) technologies and spanning the period 1981 to 2000. Hypotheses concerning the evolving nature (content and volume) of market stories in technology evolution are tested. The analysis identified four categories of market stories - technical, product availability, product adoption, and product discontinuation. The findings show that the emerging technology passes initially through a 'technical-intensive' phase whereby technology related stories dominate, through a 'supply-push' phase, in which stories presenting products embracing the technology tend to exceed technical stories while there is a rise in the number of product adoption reference stories, to a 'product-focus' phase, with stories predominantly focusing on product availability. Overall story volume declines when a technology matures as the need for sensemaking reduces. When stories about product discontinuation surface, these signal the decline of current technology. New technologies that fail to maintain the 'product-focus' stage also reflect limited market acceptance. The article also discusses the theoretical and managerial implications of the study's findings. © 2002 Elsevier Science Inc. All rights reserved.

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.

How checking breeds doubt:reduced performance in a simple working memory task

A paradox of memory research is that repeated checking results in a decrease in memory certainty, memory vividness and confidence [van den Hout, M. A., & Kindt, M. (2003a). Phenomenological validity of an OCD-memory model and the remember/know distinction. Behaviour Research and Therapy, 41, 369–378; van den Hout, M. A., & Kindt, M. (2003b). Repeated checking causes memory distrust. Behaviour Research and Therapy, 41, 301–316]. Although these findings have been mainly attributed to changes in episodic long-term memory, it has been suggested [Shimamura, A. P. (2000). Toward a cognitive neuroscience of metacognition. Consciousness and Cognition, 9, 313–323] that representations in working memory could already suffer from detrimental checking. In two experiments we set out to test this hypothesis by employing a delayed-match-to-sample working memory task. Letters had to be remembered in their correct locations, a task that was designed to engage the episodic short-term buffer of working memory [Baddeley, A. D. (2000). The episodic buffer: a new component in working memory? Trends in Cognitive Sciences, 4, 417–423]. Of most importance, we introduced an intermediate distractor question that was prone to induce frustrating and unnecessary checking on trials where no correct answer was possible. Reaction times and confidence ratings on the actual memory test of these trials confirmed the success of this manipulation. Most importantly, high checkers [cf. VOCI; Thordarson, D. S., Radomsky, A. S., Rachman, S., Shafran, R, Sawchuk, C. N., & Hakstian, A. R. (2004). The Vancouver obsessional compulsive inventory (VOCI). Behaviour Research and Therapy, 42(11), 1289–1314] were less accurate than low checkers when frustrating checking was induced, especially if the experimental context actually emphasized the irrelevance of the misleading question. The clinical relevance of this result was substantiated by means of an extreme groups comparison across the two studies. The findings are discussed in the context of detrimental checking and lack of distractor inhibition as a way of weakening fragile bindings within the episodic short-term buffer of Baddeley's (2000) model. Clinical implications, limitations and future research are considered.

Organizations in time:history, theory, methods

Book review: Organizations in Time, edited by R Daniel Wadhwani and Marcelo Bucheli, Oxford University Press, 2014. The title of this edited volume is slightly misleading, as its various contributions explore the potential for more historical analysis in organization studies rather than addressing issues associated with time and organizing. Hopefully this will not distract from the important achievement of this volume—important especially for business historians—in further expanding and integrating business history into management and organization studies. The various contributions, elegantly tied together by R. Daniel Wadhwani and Marcelo Bucheli in their substantial introduction (which, by the way, presents a significant contribution in its own right), opens up new sets of questions, especially in terms of future methodological and theoretical developments in the field. This book also reflects the changing institutional location of business historians, who increasingly make their careers in business schools rather than history departments, especially in Europe, reopening old questions of history as a social science. There have been several calls to teach more history in business education, such as the Carnegie Foundation report (2011) that found undergraduate business education too narrow in focus and highlighted the need to integrate more liberal arts teaching into the curriculum. However, in the contemporary research-driven environment of business and management schools, historical understanding is unlikely to permeate the curriculum if historical analysis cannot first deliver significant theoretical contributions. This is the central theme around which this edited volume revolves, and it marks a milestone in this ongoing debate. (In the spirit of full disclosure, I should add that even though I did not contribute to this volume, I have coauthored with several of its contributors and view this book as central to my current research practice.)