Major Histocompatibility Complex (MHC) class I receptors are glycoproteins which play a critical role in anti-viral immunity by displaying foreign peptides to cytotoxic T cell lymphocytes. The loading of high affinity peptides into the MHC class I receptor in mammals is coordinated by a multiple proteins that are collectively referred to as the peptide loading complex (PLC). To date, the composition of the peptide loading complex in fish is unknown and therefore the characterization of the molecules which may exist in this putative complex was pursued. This thesis includes the cloning and functional characterization of ERp57 and calnexin in rainbow trout which, in mammals, are known to interact with the MHC class I receptor either during its early biogenesis or later in the assembly of the PLC. Trout ERp57 and calnexin cDNA sequences are ubiquitously expressed in trout tissues and both the ERp57 and calnexin genes appear in at least two copies each in the trout genome. Interestingly, despite their high sequence identity with their mammalian homologues, some structural discrepancies were identified. ERp57 does not contain an endoplasmic reticulum (ER) retention signal or a nuclear localization signal, while one of the two isolated cDNA clones for calnexin does not contain an ER (endoplasmic reticulum) retention signal and lacks a conserved C-terminal serine phosphorylation site. These findings suggest that in trout, there may be unique versions of these proteins that have acquired different cellular functions. Through the production of polyclonal antibodies against trout ERp57, the conserved protein induction of ERp57 during ER stress was demonstrated concurrently with calnexin. In addition, this study shows for the first time that ERp57 can be induced transcriptionally by phytohemagglutinin and synthetic double stranded RNA, which implies its possible regulatory role during viral infection and the activation of the immune response. Furthermore, the functional characterization of the MHC class I specific chaperone tapasin, a key element in the PLC of mammals was pursued. Tissue and cell line distribution revealed that tapasin is expressed in high levels in immune system organs and in the rainbow trout macrophage cell line RTS11, at a relative molecular weight of 48 kDa with an additional 20 kDa band detected by the tapasin antibody. Tapasin protein was significantly up regulated upon exposure to synthetic double stranded RNA and during infection with two fish viruses: chum salmon virus and viral hemorrhagic septicemia virus genotype IVa, whereas the expression of the 20 kDa band was not affected by these stimuli. This study also examined the regulation of the MH class I heavy chain,β2 microglobulin and their associated machinery upon exposure to viral hemorrhagic septicemia virus genotype IVa at permissive and non-permissive temperatures. β2 microglobulin secretion into the cell media, a marker of MH class I receptor turnover, was detected in the conditioned media of RTS11 cells under normal conditions and was shown to be significantly enhanced during viral hemorrhagic septicemia virus genotype IVa infection. Furthermore, when RTS11 cells were maintained at cold temperatures, the secretion of β2 microglobulin was significantly reduced in both infected and non-infected cultures, while the cellular levels of β2 microglobulin remained unchanged. These results suggest that cold temperature can alter the expression of the MH class I molecule on the cell surface and therefore may be contributing to host susceptibility to viral hemorrhagic septicemia virus genotype IVa during the winter. Lastly, Co-immunoprecipitation demonstrated the interaction of the lectin chaperones: calnexin and calreticulin with the glycosylated MH class I receptor supporting their conserved role during MH class I receptor folding in fish. Concurrently, tapasin's interaction with transporter associated with antigen processing (TAP) and with the glycosylated form of the MH class I was revealed for the first time in fish, which supports their role in antigen presentation as in mammals. This study demonstrated that ERp57 and tapasin form a conserved disulfide linked heterodimer of 110 kDa, however unlike mammals, an additional 75 kDa heterodimer was detected which suggests a possible novel interaction of ERp57 with a 20 kDa tapasin version alternately regulating antigen presentation in fish. Overall, this study suggest that the interactions involved in antigen presentation in mammals are conserved in fish, however the presence of different protein versions of calnexin, ERp57 and tapasin might dictate a different mode of regulation for MH class I assembly in fish, as opposed to mammals. Elucidating these interactions during various viral infections in fish can help to uncover possible viral strategies to manipulate the host immune response and will provide information needed to assist in designing novel tools to prevent fish viral diseases.

Rökare får allt mer mindre utrymme att röka på och det blir allt mindre socialt accepterat att röka i dagens samhälle. Syftet med vår uppsats är att undersöka hur rökaren upplever samhällets normer och negativitet kring rökning, samt hur detta påverkar dem. Vår huvudsakliga frågeställning har varit ”Hur påverkas rökare av samhället nedvärderande syn på rökning?”, men även om det finns någon skillnad i deras rökningsbeteende beroende på social situation. Studien är gjord med hjälp av en kvalitativ metod i form av intervjuer, där vi intervjuat 6 rökare allt ifrån åldern 23-70. Vi har använt oss utav Goffmans intrycksstyrningoch Harveys rumsbegreppför att kunna förklara ur ett sociologiskt perspektiv hur rökaren upplever samhället och hur det påverkar denne. Vårt resultat har visat att rökare anpassar sig väldigt mycket till den sociala situationen, samt tar hänsyn till andra och att rökare kartlägger sin rökning grundat på tid, rum och social situation. / Smokersgetincreasinglyless roomto smokeanditis becoming lesssociallyacceptable to smokeintoday's society.The purpose of ourpaper is to examinehowthe smokerexperiencingsocial normsandnegativity surroundingsmoking,andhow this affectsthem. Our mainresearch questionwas"How does the negative view on smoking in today’s society affect smokers?”, but also if there is any differenceintheir smokingbehaviordepending on thesocial situation.The study was conductedusinga qualitative approachin the form ofinterviews, wherewe interviewedsixsmokersranging fromages23-70. We have usedGoffman'spresentation of SelfandHarveysspace theory to explainfrom a sociological perspectivehowsmokersperceivesociety andhow it affectshim.Ourresults have shownthat smokers arevery adaptedtothe social situation, they are considerate andthat smokerscharttheir smokingbased on thetime, placeand social situation.

Adenoviral CD40L gene therapy (AdCD40L) is a strong inducer of anti-tumor immune responses via its activation of dendritic cells (DCs). Activated DCs can in turn activate T cells, which are key players in an efficient anti-tumor response. This thesis includes three papers that focus on different aspects of AdCD40L gene therapy. In the first paper, the infiltration of suppressive CD11b+Gr-1+ cells in orthotopic MB49 bladder tumors was investigated and found to be significantly reduced while activated T cells were increased when the tumors had been treated with local AdCD40L gene therapy. Further, AdCD40L could tilt the cells in the tumor microenvironment in favor of an efficient anti-tumor immunity (M1 macrophages and activated T cells) instead of an immunosuppressive environment (CD11b+Gr-1int/low myeloid cells and M2 macrophages). Immunotherapy combined with chemotherapy has shown promising results, and the second paper investigates the combination of AdCD40L gene therapy together with the chemotherapeutic drug 5-Fluorouracil (5-FU). A synergistic effect of the combination treatment on orthotopic MB49 bladder tumors could be demonstrated. The combination therapy resulted in decreased tumor growth, increased survival and systemic MB49-specific immunity, whereas AdCD40L or 5-FU therapy alone had a poor effect on tumor growth. Efficient AdCD40L therapy is dependent on high transduction efficiency in both cancer cells and cells present in the tumor microenvironment. In an attempt to enhance the transduction efficiency, and thereby the therapeutic efficacy, a modified adenovirus was developed for paper three. This modified Ad5PTDf35(mCD40L) could, in comparison with the unmodified Ad5(mCD40L), demonstrate increased transduction capacity of a variety of murine cells. Further, the ability of antigen presenting cells (APCs) to present antigens to T cells was improved after transduction with Ad5PTDf35(mCD40L).

Background: The incidence of caesarean section for breech presentation has reached approximately 90 % in Sweden. In many of these cases, by means of specific selection criteria, it would be as safe to plan for vaginal breech delivery.   Aim: The objective of this study was to investigate differences in management and to compare maternal and fetal outcomes according to delivery mode of breech presentation; vaginal vs. caesarian section. The study included breech presentation in full term singleton pregnancies at the UppsalaUniversityHospital, Uppsala, Sweden (UAS).   Method: The study was based on medical record data with a retrospective, descriptive, comparative design with quantitative approach. The method for data collection was a manual review of patient records using a structured questionnaire.   Results: Of the women with children in breech presentation during the period studied, 11 % gave birth vaginally. Mother's wish was the most common cause of caesarean section. The group with caesarean section included more first-time mothers, longer length of stay at the hospital, increased bleeding and need for pain medication, separation from the child, later lactation and earlier introduction of formula. Vaginally delivered mothers had increased incidence of straight urine catheterization postpartum and of infants with lower Apgar scores.   Conclusion: This study does not support the suggestion that it would be safer to give birth by caesarean section for breech presentation in cases where the woman at full term meets strict selection criteria. Instead of applying medical criteria, the decision regarding mode of delivery was more often left up to the mother.

A growing body of literature is focusing on the influence of personality and emotion regulation on psychological health. Using archival data from an expressive writing project, the current study investigated the relationship between perfectionistic self-presentation and emotion regulation, and the influence of the interaction of these variables on psychological health among trauma survivors. The results indicate that both perfectionistic self-presentation and more difficulties in emotion regulation contribute to symptoms of distress. As well, higher levels of perfectionistic self-presentation were associated with more difficulties in emotion regulation. Further, emotion regulation mediated the relationship between perfectionistic self-presentation and psychological distress but not common physical complaints. More specifically, the non-acceptance subscale of emotion regulation was found to be significant in a test of multiple mediator model.

This thesis is an architectural study surveying on miniature parks and miniature models exhibited in them and particularly focuses on Miniaturk - the first miniature park of Turkey- located in Istanbul. It is established as an environment containing a group of miniature models of buildings and landscapes, which display the variety, and richness of the cultural tradition of the previous and contemporary Anatolian civilizations, and especially Ottoman grandeur. In this study, it is argued that Miniaturk stands as a hybrid category between a museum, a public park and entertainment centre. Miniaturk is also conceived as an architectural environment providing a possible ground to discuss the conceptions, misconceptions and presuppositions about architecture in the popular realm and in the professional and disciplinary framework. Thereby, Miniaturk is investigated through the processes of its production including the initial design idea and all the stages of its construction. This study also tries to discuss the miniature models from different points of view. Whether they are considered as tools of architectural representation or not by the professionals, the popularity and the communicative advantage of these models can be used to arouse interest in the cultural and historical heritage as well as the contemporary architecture. The daily life of man on the street is strictly connected with architecture / therefore Miniaturk requires recognition as an environment for realization of these connections and relations.

ABSTRACT PRESENTATION OF CLASSICAL ARCHAEOLOGICAL SITES IN VIRTUAL ENVIRONMENT CASE STUDY: SAGALASSOS BASAgA&Ccedil / , &Ouml / zge M.S, Department of Architecture in Restoration Supervisor: Dr. Fuat G&Ouml / K&Ccedil / E July 2005, 123 pages Parallel to the growing concern for the protection and presentation of archaeological sites, virtual environments (VE) are in use for visualization purposes since mid 1980&rsquo / s. This thesis investigates the potentials and problems of presenting a classical archaeological site in VE from the viewpoint of conservation science, to ensure the welfare of the remains. The study is handled in two sections as a conceptual part and a case study. The conceptual part, first dwells upon the history, aim and techniques of the VE presentations. This section ends with the development of criteria for the evaluation of VE presentations of classical archaeological sites. For the case study, the antique city of Sagalassos is investigated through its history, urban tissue, architecture, multidisciplinary studies and VE projects. The thesis concludes with general remarks on the presentation of classical archaeological sites in VE and proposes some solutions to improve the presentation of Sagalassos in particular.

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