MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors

T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design.

Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells

Dendritic cells (DCs) are able to present glycolipids to invariant natural killer T (iNKT) cells in vivo. Very few compounds have been found to stimulate iNKT cells, and of these, the best characterised is the glycolipid a-galactosylceramide, which stimulates the production of large quantities of interferon-gamma (IFN-?) and interleukin-4 (IL-4). However, aGalCer leads to overstimulation of iNKT cells. It has been demonstrated that the aGalCer analogue, threitol ceramide (ThrCer 2), successfully activates iNKT cells and overcomes the problematic iNKT cell activation-induced anergy. In this study, ThrCer 2 has been inserted into the bilayers of liposomes composed of a neutral lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), or dimethyldioctadecylammonium bromide (DDA), a cationic lipid. Incorporation efficiencies of ThrCer within the liposomes was 96% for DSPC liposomes and 80% for DDA liposomes, with the vesicle size (large multilamellar vs. small unilamellar vesicles) making no significant difference. Langmuir-Blodgett studies suggest that both DSPC and DDA stack within the monolayer co-operatively with the ThrCer molecules with no condensing effect. In terms of cellular responses, IFN-? secretion was higher for cells treated with small DDA liposomes compared with the other liposome formulations, suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs.

Topographic studies of scalp potentials evoked by pattern presentation

The waveform and scalp distribution of the visual evoked potentials elicited by stimuli in the foveal and parafoveal regions have been investigated in a group of normal humans using a 16-channel `brain mapping' system. The waveform and topography of the responses to pattern onset and pattern reversal stimulation were investigated, using 4 x 4o full field and 4 x 2o lateral and altitudinal half-field stimuli. The responses were composed of several successive peaks which are in some respects consistent with those demonstrated by other workers using larger field sizes. The differences in the behaviour of these components with respect to the position of the stimulus in the visual field were suggestive of origins in different areas of the visual cortex and/or different visual mechanism. Of particular interest were the major early positive components `P90' and `P95' of the responses to pattern onset and pattern reversal stimulation respectively. More detailed exploration of the behaviour of these major early positive components was carried out using `M-scaled' stimuli selected to activate one square centimetre patches of striate cortex and associated extrastriate re-projections, positioned at different points in the foveal and parafoveal area of the visual field. The inter- and intra-subject variability in amplitude and localisation of the signals elicited by these targets was considered to be a reflection of the individual variations in relationship of visual field projections with the pattern of gyri and fissures on the proximal surface of the occipital lobe. The behaviour of component P90 of the onset response is consistent with a lateral origin in extrastriate visual cortex; that of P95 of the pattern reversal response is consistent in some respects with a striate cortical origin, but in others with a partial origin in extrastriate cortex.

Consumer responses to really new products: examining the impacts of learning strategies and presentation formats on product comprehension and attitude formation

Mental simulations and analogies have been identified as powerful learning tools for RNPs. Furthermore, visuals in advertising have recently been conceptualized as meaningful sources of information as opposed to peripheral cues and thus may help consumers learn about RNPs. The study of visual attention may also contribute to understanding the links between conceptual and perceptual analyses when learning for a RNP. Two conceptual models are developed. the first model consists of causal relationships between the attributes of advertising stimuli for RNPs and consumer responses, as well as mediating influences. The second model focuses on the role of visual attention in product comprehension as a response to advertising stimuli. Two experiments are conducted: a Web-Experiment and an eye-tracking experiment. The first experiment (858 subjects) examines the effect of learning strategies (mental simulation vs. analogy vs. no analogy/no mental simulation) and presentation formats (words vs. pictures) on individual responses. The mediating role of emotions is assessed. The second experiment investigates the effect of learning strategies and presentation formats on product comprehension, along with the role of attention (17 subjects). The findings from experiment 1 indicate that learning strategies and presentation formats can either enhance or undermine the effect of advertising stimuli on individual responses. Moreover, the nature of the product (i.e. hedonic vs. utilitarian vs. hybrid) should be considered when designing communications for RNPs. The mediating role of emotions is verified. Experiment 2 suggests that an increase in attention to the message may either reflect enhanced comprehension or confusion.

Developing a complex intervention to reduce time to presentation with symptoms of lung cancer

Background - Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases. Aim - To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer. Design and setting - Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland. Method - The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients. Results - First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient–general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised. Conclusion -The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.

Risks and benefits of selective (re)presentation of interviewees' talk:some insights from discourse analysis

Purpose: The purpose of this paper is to examine the quality of evidence collected during interview. Current UK national guidance on the interviewing of victims and witnesses recommends a phased approach, allowing the interviewee to deliver their free report before any questioning takes place, and stipulating that during this free report the interviewee should not be interrupted. Interviewers, therefore, often find it necessary during questioning to reactivate parts of the interviewee's free report for further elaboration. Design/methodology/approach: The first section of this paper draws on a collection of police interviews with women reporting rape, and discusses one method by which this is achieved - the indirect quotation of the interviewee by the interviewer - exploring the potential implications for the quality of evidence collected during this type of interview. The second section of the paper draws on the same data set and concerns itself with a particular method by which information provided by an interviewee has its meaning "fixed" by the interviewer. Findings: It is found that "formulating" is a recurrent practice arising from the need to clarify elements of the account for the benefit of what is termed the "overhearing audience" - in this context, the police scribe, CPS, and potentially the Court. Since the means by which this "fixing" is achieved necessarily involves the foregrounding of elements of the account deemed to be particularly salient at the expense of other elements which may be entirely deleted, formulations are rarely entirely neutral. Their production, therefore, has the potential to exert undue interviewer influence over the negotiated "final version" of interviewees' accounts. Originality/value: The paper highlights the fact that accurate re-presentations of interviewees' accounts are a crucial tool in ensuring smooth progression of interviews and that re-stated speech and formulation often have implications for the quality of evidence collected during significant witness interviews. © Emerald Group Publishing Limited.

Cortical dynamics and synchronization related to multiple target consolidation under rapid-serial-visual-presentation conditions

The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system’s overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called “attentional blink” (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.

Use of Knowledge Technologies for Presentation of Bulgarian Folklore Heritage Semantics

Preserving and presenting the Bulgarian folklore heritage is a long-term commitment of scholars and researchers working in many areas. This article presents ontological model of the Bulgarian folklore knowledge, exploring knowledge technologies for presenting the semantics of the phenomena of our traditional culture. This model is a step to the development of the digital library for the “Bulgarian Folklore Heritage” virtual exposition which is a part of the “Knowledge Technologies for Creation of Digital Presentation and Significant Repositories of Folklore Heritage” project.

Electronic Presentation of Bulgarian Educational Archives: an Ontology-Based Approach

The paper presents an ongoing effort aimed at building an electronic archive of documents issued by the Bulgarian Ministry of Education in the 40ies and 50ies of the 20th century. These funds are stored in the Archive of the Ministry of the People’s Education within the State Archival Fund of the General Department of Archives at the Council of Ministers of Bulgaria. Our basic concern is not the digitization process per se, but the subsequent organization of the archive in a clear and easily-searchable way which would allow various types of users to get access to the documents of interest to them. Here we present the variety of the documents which are stored in the archival collection, and suggestions on their electronic organization. We suggest using ontologies- based presentation of the archive. The basic benefit of this approach is the possibility to search the collection according to the stored content categories.

XML Presentation of Documents Used for Data Exchange in Management of Genetic Resources

In the global strategy for preservation genetic resources of farm animals the implementation of information technology is of great importance. In this regards platform independent information tools and approaches for data exchange are needed in order to obtain aggregate values for regions and countries of spreading a separate breed. The current paper presents a XML based solution for data exchange in management genetic resources of farm animals’ small populations. There are specific requirements to the exchanged documents that come from the goal of data analysis. Three main types of documents are distinguished and their XML formats are discussed. DTD and XML Schema for each type are suggested. Some examples of XML documents are given also.

Digital Preservation and Access to Cultural and Scientific Heritage: Presentation of the KT-DigiCult-BG Project

The fast development and wide application of digital methods, combined with broadened access to the Internet and falling computing costs, have created intense interest in electronic presentation and access to cultural and scientific heritage resources. Information technologies have offered cultural institutions new opportunities for the presentation of their holdings, which are now made accessible not only to the specialists, but also to the citizens and interested parties worldwide. The paper presents an overview of the Bulgarian experience in the field of digital preservation and access and on-going work on the project “Knowledge Transfer for the Digitisation of Scientific and Cultural Heritage to Bulgaria” (MTKD-CT-2004-509754) supported by the Marie Curie programme of the FP6 of the EC.