MHC-restricted antigen presentation and recognition: constraints on gene, recombinant and peptide vaccines in humans

The target of any immunization is to activate and expand lymphocyte clones with the desired recognition specificity and the necessary effector functions. In gene, recombinant and peptide vaccines, the immunogen is a single protein or a small assembly of epitopes from antigenic proteins. Since most immune responses against protein and peptide antigens are T-cell dependent, the molecular target of such vaccines is to generate at least 50-100 complexes between MHC molecule and the antigenic peptide per antigen-presenting cell, sensitizing a T cell population of appropriate clonal size and effector characteristics. Thus, the immunobiology of antigen recognition by T cells must be taken into account when designing new generation peptide- or gene-based vaccines. Since T cell recognition is MHC-restricted, and given the wide polymorphism of the different MHC molecules, distinct epitopes may be recognized by different individuals in the population. Therefore, the issue of whether immunization will be effective in inducing a protective immune response, covering the entire target population, becomes an important question. Many pathogens have evolved molecular mechanisms to escape recognition by the immune system by variation of antigenic protein sequences. In this short review, we will discuss the several concepts related to selection of amino acid sequences to be included in DNA and peptide vaccines.

Linguistic models for decision support

Linguistic modelling is a rather new branch of mathematics that is still undergoing rapid development. It is closely related to fuzzy set theory and fuzzy logic, but knowledge and experience from other fields of mathematics, as well as other fields of science including linguistics and behavioral sciences, is also necessary to build appropriate mathematical models. This topic has received considerable attention as it provides tools for mathematical representation of the most common means of human communication - natural language. Adding a natural language level to mathematical models can provide an interface between the mathematical representation of the modelled system and the user of the model - one that is sufficiently easy to use and understand, but yet conveys all the information necessary to avoid misinterpretations. It is, however, not a trivial task and the link between the linguistic and computational level of such models has to be established and maintained properly during the whole modelling process. In this thesis, we focus on the relationship between the linguistic and the mathematical level of decision support models. We discuss several important issues concerning the mathematical representation of meaning of linguistic expressions, their transformation into the language of mathematics and the retranslation of mathematical outputs back into natural language. In the first part of the thesis, our view of the linguistic modelling for decision support is presented and the main guidelines for building linguistic models for real-life decision support that are the basis of our modeling methodology are outlined. From the theoretical point of view, the issues of representation of meaning of linguistic terms, computations with these representations and the retranslation process back into the linguistic level (linguistic approximation) are studied in this part of the thesis. We focus on the reasonability of operations with the meanings of linguistic terms, the correspondence of the linguistic and mathematical level of the models and on proper presentation of appropriate outputs. We also discuss several issues concerning the ethical aspects of decision support - particularly the loss of meaning due to the transformation of mathematical outputs into natural language and the issue or responsibility for the final decisions. In the second part several case studies of real-life problems are presented. These provide background and necessary context and motivation for the mathematical results and models presented in this part. A linguistic decision support model for disaster management is presented here – formulated as a fuzzy linear programming problem and a heuristic solution to it is proposed. Uncertainty of outputs, expert knowledge concerning disaster response practice and the necessity of obtaining outputs that are easy to interpret (and available in very short time) are reflected in the design of the model. Saaty’s analytic hierarchy process (AHP) is considered in two case studies - first in the context of the evaluation of works of art, where a weak consistency condition is introduced and an adaptation of AHP for large matrices of preference intensities is presented. The second AHP case-study deals with the fuzzified version of AHP and its use for evaluation purposes – particularly the integration of peer-review into the evaluation of R&D outputs is considered. In the context of HR management, we present a fuzzy rule based evaluation model (academic faculty evaluation is considered) constructed to provide outputs that do not require linguistic approximation and are easily transformed into graphical information. This is achieved by designing a specific form of fuzzy inference. Finally the last case study is from the area of humanities - psychological diagnostics is considered and a linguistic fuzzy model for the interpretation of outputs of multidimensional questionnaires is suggested. The issue of the quality of data in mathematical classification models is also studied here. A modification of the receiver operating characteristics (ROC) method is presented to reflect variable quality of data instances in the validation set during classifier performance assessment. Twelve publications on which the author participated are appended as a third part of this thesis. These summarize the mathematical results and provide a closer insight into the issues of the practicalapplications that are considered in the second part of the thesis.

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93% of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97% of patients were cured, with increases in bone mineral density of 19.4% in the lumbar spine and 15.7% in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients.

Effect of the Knowledge Representation Form on the Efficiency of Knowledge Sharing

The goal of this thesis is to estimate the effect of the form of knowledge representation on the efficiency of knowledge sharing. The objectives include the design of an experimental framework which would allow to establish this effect, data collection, and statistical analysis of the collected data. The study follows the experimental quantitative design. The experimental questionnaire features three sample forms of knowledge: text, mind maps, concept maps. In the interview, these forms are presented to an interviewee, afterwards the knowledge sharing time and knowledge sharing quality are measured. According to the statistical analysis of 76 interviews, text performs worse in both knowledge sharing time and quality compared to visualized forms of knowledge representation. However, mind maps and concept maps do not differ in knowledge sharing time and quality, since this difference is not statistically significant. Since visualized structured forms of knowledge perform better than unstructured text in knowledge sharing, it is advised for companies to foster the usage of these forms in knowledge sharing processes inside the company. Aside of performance in knowledge sharing, the visualized structured forms are preferable due the possibility of their usage in the system of ontological knowledge management within an enterprise.

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).

Cheque Presentation

Members of the Niagara Peninsula Joint Committee on Higher Education receiving cheques for their cause. Ivan Buchanan is second from the left and on the far right are Robert Schmon and his father Arthur Schmon (Chairman of the Committee).

Alumni Association Cheque Presentation

Presentation of the Alumni Association cheque at the sod turning ceremonies for the Science Complex in 1982. Pictured here from left to right are: R. Misener, Chancellor; Geoff Borland, president, Alumni Assocation; Ginny Gilbert, Alumni Officer; and Don Bethune, honorary chairman for Alumni Association Fundraising.

1970 Design Presentation

Pictured here from left to right are Chairman of the Board, Whiting Lathrop, President James Gibson, and Architect Raymond Moriyama during the formal presentation of the $7.7 million MacKenzie Chown Complex project, which at the time was known as the Academic Staging Building or simply East Block.

UAW Presentation

Pictured here from left to right are James Hogan, University Librarian, Dr. James Gibson, President, and William Marshal of the UAW.

Commerative Stamp Presentation

Pictured here from left to right are James Hogan, Librarian, and President James Gibson with a set of stamps commerating Sir Isaac Brock that were issued from the Bailiwick of Guernsey in October of 1969.

(Re)writing the other/self : autoethnography in the transcultural arena of representation

Abstract: In Imperial Eyes Mary Louise Pratt (1992: 7, emphasis original) defines autoethnography as "instances in which colonized subjects undertake to represent themselves in ways that engage with the colonizer's own terms ... in response to or in dialogue with . . . metropolitan representations." Although Pratt's conceptualization of autoethnography has much to offer post-colonial studies, it has received little attention in the field. In this thesis, I interrogate Pratt's notion of autoethnography as a theoretical tool for understanding the self-representations of subordinate peoples within transcultural terrains of signification. I argue that autoethnography is a concept that allows us to move beyond some theoretical dualisms, and to recognize the (necessary) coexistence of subordinate peoples' simultaneous accommodation of and resistance to dominant representations of themselves. I suggest that even when autoethnographic expressions seem to rely on or to reproduce dominant knowledges, their very existence as speech acts implicitly resists dominant discourses which objectify members of oppressed populations and re-create them as Native Informants. I use Pratt's concept to analyze two books by Islamic feminist sociologist Fatima Memissi. Memissi's Dreams ofTrespass and Scheherazade Goes West illustrate the simultaneity of accommodation and disruption evident in autoethnographic communication. Across the two books, Memissi shows herself renegotiating the discourses which discipline her (and her speech). She switches back and forth between the positions of reader and author, demonstrates the reciprocity of the disciplinary gaze (she looks back at her dominants, reading their own reading of her representation of her social group), and provides a model of autoethnographic dialogue.