Hepatitis C Virus (HCV) is a global health problem, with over 170 million infected individuals worldwide. 70-80% of infected individuals develop progressive disease, and approximately 2% of these acquire hepatocellular carcinoma (HCC). HCV entry is dependent on tetraspanin CD81, scavenger receptor BI, and tight junction proteins claudin-1 and occludin. Tetraspanins are involved in multiple biological functions including cell-ECM adhesion and motility. An actin polymerization-dependent cell spread was observed upon ligation of CD81 on hepatoma cells. Importantly, HCV infection perturbed CD81-dependent cell spread, suggesting HCV infection may modulate CD81 function in hepatoma cells. Functional assays demonstrated that CD81 expression and HCV infection promote hepatoma cell motility. These findings allude to a link between HCV infection and associated HCC development. Establishment of a chronic infection demonstrates that HCV can escape from the host adaptive immune responses. We developed an in vitro cell culture system to monitor viral transmission in the presence of neutralizing antibodies (nAb). Separation of producer and target cells ablated nAb resistant transmission, suggesting that cell-cell contact was essential. Furthermore nAb resistant transmission was dependent upon all four co-receptors. These observations confirm HCV immune evasion by cell-to-cell transfer and have major implications for anti-glycoprotein targeted therapies.

CD4+ T cells play a key role in orchestrating adaptive immunity. Their activation requires antigen presentation via MHC II proteins on antigen presenting cells (APC). Exosomes are membrane vesicles released by various cell types including APCs. APC-derived exosomes are MHC class II-positive and can induce CD4+ T cell responses. MHC II delivery to the cell surface and/or exosomes might be influenced by tetraspanins, a family of transmembrane proteins. We have prepared exosomes derived from Epstein-Barr virus (EBV)-infected human B lymphoblastoid cell lines (LCLs) and shown by Western blotting and immunoelectron microscopy that they contain MHC class II and tetraspanins including CD63, CD81 and CD82. Such LCLs as well as LCL-derived exosomes can mediate immunologically specific recognition by MHC class II matched EBV antigen-specific CD4+ T cell clones when directly added to the T cells. Using shRNA, we have decreased CD63 expression in LCLs and had been studying the effect of such downregulation on LCL as well as LCL-derived exosome mediated antigen presentation. Despite an unaltered level of MHC II, CD63low LCLs showed to be hyperstimulatory. In spite of a similar depletion of CD63 in exosomes derived from CD63low LCLs, the CD4+ T cell stimulation by these exosomes was unaltered. In search for the mechanism of this phenomenon we found a higher level of exosome secretion by CD63low LCLs. We speculate that CD63 may influence T cell stimulation by exosome trafficking as well as exosome release.

This thesis summarises a selection of forty-two studies [1-42], published by the author during the period 2000-2012, investigating the conceptual basis of Insomnia Disorder, and its evaluation and treatment, principally using cognitive and behavioural interventions. The work reflects a range of research methodologies including experimental, psychometric, qualitative and population-based studies, and randomised controlled trials. Important theoretical contributions to the literature published in this period are also included and reference is made to major textbooks, position papers, and influential chapter contribution.

It is a widely debated subject whether a patient with a diagnosis of major depression and a history of psychosis is able to use and comprehend metaphors. There are a number of studies that indicate that metaphor comprehension with this population is very reduced. However, within the context of psychotherapy metaphor is poorly defined and the concept is often applied inconsistently in academic literature. This thesis examines a commonly reported occurrence of metaphor formation in art psychotherapy and in particular, examines a type of metaphor that offers a novel perspective about interpersonal relationships called the creative relationship metaphor. This thesis aims to develop a definition of a form of metaphor that is helpful in clinical practice and understand the clinical formation of this metaphor in art psychotherapy. The first part of the thesis develops a new metaphor type, called the ‘creative relationship metaphor’ (CRM), beginning with a psycholinguistic perspective. 2 3 In summary, the key characteristics of the CRM being developed is that it is: • An interpersonal event • An image based representation which is cognitively mapped • Context dependent • A novel way of perceiving the person, thing or event The hypothesis that patients diagnosed with severe mental health issues can produce CRMs is tested through two analyses. The first analysis focuses on the defining features of the creative relationship metaphor and the second analysis focuses on the therapist’s influence on metaphor formation. In the clinical examples, the increased capacity to reflect on significant relationships is linked to the formation of the CRM. These results offer preliminary evidence suggesting that there are specific in-session interventions that support the development of the CRM in the assessment context.

This thesis describes the design and workflow of creating an image processing application in Android system, and what are the possibilities in choosing development environment and how to implement them. Then I am writing about my solutions of creating applications, graphical user interface and an interface for Android. I am describing my approach in the design and functionality of the application, communication with the camera, storing and retrieving data. Further I explain which algorithms were implemented for image processing and image evaluation. Product of this thesis is a functioning application that allows to its user to capture images and video stream. The algorithm evaluates the entering data and shows the location of the number plate. The application also allows recognizing texts and numbers from images. There are other various practical features and options implemented within the application.

Volume one represents the research component of the qualification, and is comprised of a conceptual literature review and a qualitative research paper. The conceptual review analysed a small sample of the qualitative literature on couplehood and dementia. The analysis used Dialogic/Performance Analysis (Reissman, 2008) to provide critical commentary about the implications of participant voice, linguistic features and context in research papers, and how these may uncover possible narratives that are embedded in the literature. Implications of embedded narratives have been discussed. The research portion is a piece of qualitative research that used Interpretative Phenomenological Analysis. The theoretical underpinning is that of Systemic psychology. Three couples were recruited (the husbands were all diagnosed with dementia). The couples have been presented as case studies showing themes that emerged between the partners in the couples. The discussion focuses on the perceptions of continuity/discontinuity in the relationship and shared and unshared narratives. Clinical implications and directions for future research have been proposed. Volume two represents the clinical aspects of this qualification and is comprised of five clinical case reports: A case study using dual formulation, a small scale service-related research (service evaluation), single-case experimental design, case study and the abstract from an oral presentation.

Due to concerns about international differences in treatment effectiveness, many countries are reluctant to extrapolate overseas clinical data to form the basis of guideline recommendations and intervention approval processes. The evidence on which these concerns are based, however, comes from a limited dataset, with few studies directly assessing international differences in treatment effectiveness. This study aims to assess differences in the results of cardiovascular trials between Europe, North America, and Asia using the panoramic meta-analysis approach. All meta-analyses containing randomised control trials for the treatment or prevention of cardiovascular diseases were searched for in The Cochrane Library (2000 to 2008) and Medline (2005-2008). Analysis was then conducted within and over the included meta-analyses by performing pair-wise comparisons of the trial results between Europe and North America, Europe and Asia, and North America and Asia and a universal comparison of all three continents’ trial results together. All analyses were conducted over fatal and non-fatal endpoints. The findings suggested that for both endpoints, interventions performed best in Asian trials. For fatal endpoints, a high proportion of positive trial results were observed for Japan. Further investigation showed that between-continent differences in treatment effect could be explained by between-continent differences in trial quality. However, the types of intervention prone to inter-continental differences could not be identified for fatal or non-fatal endpoints. These findings suggest that those developing guidelines and approving interventions should be cautious when extrapolating overseas data. In particular, this study highlights the importance of taking trial quality into account when extrapolating and interpreting clinical trial data from different regions.

Interpretations of osteological remains from mainland Greece during the 1960-1980s led to the suggestion that the most virulent form of malaria, Plasmodium falciparum, was prevalent between the Mesolithic and Late Bronze Age (c. 8700 cal. BC-1100 cal. BC). Although disregarded over the past decade, the theory has regained support in recent years from osteological, epidemiological, environmental and DNA studies. However, the presence of this strain of malaria in prehistoric Greece remains controversial. This thesis evaluates 1) the palaeoclimatic conditions of the Aegean between the Mesolithic and Late Bronze Age and 2) the palaeoenvironmental conditions of three archaeological settlements, with the aim of ascertaining whether the climatic and environmental conditions were as conducive for P. falciparum and the mosquito vectors as the osteological evidence suggested. Equal consideration is given to the so-called ‘lesser strains’ of malaria, P. vivax and P. malariae, the significance of which is considered to have been underestimated in previous studies.

Applicants to Medical School must be academically successful to secure a place at university. Despite their success in secondary education and the stringent entry criteria, a significant number of students fail summative assessments at the end of their First Year. This gives rises to the following question: “Why do previously high achieving students fail in the university system?” Existing models seek to distinguish between voluntary and involuntary withdrawal from university and to explain academic withdrawal in the context of an individual’s academic and social integration into a new educational environment, their commitment to the institution and their commitment to Medicine as a career. However, much of the existing literature on failure in the early years at Medical School has focused on pre-university academic ability, as demonstrated by grade achievement at the end of secondary education, and/or faculty’s perspectives of student failure. This dissertation adopts a qualitative approach to understanding success and failure in the first year at Medical School from the perspective of medical students themselves. Their perspectives are explored within the model of withdrawal and persistence proposed by Tinto (1975) and interpreted in the context of existing literature on failure in the early years of higher education in general and in Medicine in particular. These findings are further reframed within an analysis based upon Bourdieu’s Theory of Practice. This analysis considers the students’ field of operation, the relative positions of agents within the field and the capitals which allow them to hold those positions, and the habitus of the agents and the institution itself. Through this analysis, factors that students believe may predispose to success and failure are identified and discussed. This in turn leads to a consideration of how my own understanding and professional practice have developed and might develop in the future.

Low power, high speed serial transceivers are employed in a wide range of applications ranging from chip-to-chip, backplane, and optical interconnects. Apart from being capable of handling a wide range of data rates, the transceivers should have low power consumption (mW/Gbps) and be fully integrated. This work discusses enabling techniques to implement such transceivers. Specifically, three designs: (1) a 0.5-4 Gbps serial link which uses current recycling to reduce power dissipation and (2) a 0.5-2.5 Gbps reference-less clock and data recovery circuit which uses a novel frequency detector to achieve unlimited acquisition range and (3) a 2-4 Gbps low power receiver architecture capable of resolving multiple signalling formats with a simplified XOR based phase rotating PLL will be presented. All the three circuit topologies are highly digital and aim to address the requirements of wide operating range, low power dissipation while being fully integrated. Measured results obtained from the prototypes illustrate the effectiveness of the proposed design techniques. / Graduation date: 2012 / Access restricted to the OSU Community at author's request from Dec. 2, 2011 - June 2, 2012