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In this thesis, two applications of dimensional deconstruction are studied. The first application is a model for neutrino oscillations in the presence of a large decon- structed extra dimension. In the second application, Kaluza{Klein dark matter from a latticized universal extra dimension is studied. The goal of these projects have been twofold. First, to see whether it is possible to reproduce the relevant features of the higher-dimensional continuum theory, and second, to examine the effect of the latticization in experiments. In addition, an introduction to the the- ory of dimensional deconstruction as well as to the theory of continuous extra dimensions is given. Furthermore, the various higher-dimensional models, such as Arkani-Hamed{Dvali{Dimopolous (ADD) models and models with universal extra dimensions, that have been intensively studied in recent years, are discussed. / QC 20101202

Artificial Neural Networks are successfully solving a wide range of problems with impressive performance. Nevertheless, often very little or nothing is understood in the workings behind these black-box solutions as they are hard to interpret, let alone to explain. This thesis proposes a set of complementary interpretable visualization models of neural activity, developed through prototyping, to answer the research question ”How may neural activity of Recurrent Neural Networks for text sequence prediction be represented, transformed and visualized during the inference process to explain interpretable functionality with respect to the text domain of some individual hidden neurons, as well as automatically detect these?”. Specifically, a Vanilla and a Long Short-Term Memory architecture are utilized for character respectively word prediction as testbeds. The research method is experimental; causalities between text features triggering neurons and detected patterns of corresponding nerve impulses are investigated. The result reveals not only that there exist neurons with clear and consistent feature-specific patterns of activity, but also that the proposed models of visualization successfully may automatically detect and interpretably present some of these. / Artificiella Neurala Nätverk löser framgångsrikt ett brett spektrum av problem med imponerande prestanda. Ändå är det ofta mycket lite eller ingenting som går att förstå bakom dessa svart-låda-lösningar, eftersom de är svåra att tolka och desto svårare att förklara. Den här uppsatsen föreslår en uppsättning komplementerande tolkningsbara visualiseringsmodeller av neural aktivitet, utvecklad genom prototypering, för att besvara forskningsfrågan ”Hur kan användningsprocessen av Rekurrenta Neurala Nätverk för textgenerering visualiseras på ett sätt för att automatiskt detektera och förklara tolkningsbar funktionalitet hos några enskilda dolda neuroner?”. Specifikt används en standardoch en LSTM (långt korttidsminne)-arkitektur för teckenrespektive ordprediktering som testbäddar. Forskningsmetoden är experimentell; orsakssamband mellan specifika typer av tecken/ord i texten som triggar neuroner, och detekterade mönster av motsvarande nervimpulser undersöks. Resultatet avslöjar inte bara att neuroner med tydliga och konsekventa tecken/ord-specifika aktivitetsmönster existerar, men också att de utvecklade modellerna för visualisering framgångsrikt kan automatiskt upptäcka och tolkningsbart presentera några av dessa.

<p> The ErbB2/Neu orphan receptor tyrosine kinase is amplified in 20-30% of breast and ovarian cancers and predicates poor patient prognosis. Five conserved tyrosine residues, autophosphorylated by Neu catalytic activity, "dock" adaptors and second messengers that activate discrete signalling pathways, most prominently the Ras/MAPK pathway, to regulate cell survival and proliferation. </p> <p> Genetic analysis using Drosophila provides an efficient means for identifying evolutionarily conserved signalling components. Neu and Drosophila EGFR overexpression directs Drosophila tissue development synonymously. Consistent with biochemical evidence, genetic analysis ofNeu signalling through individual pTyr revealed activating signals for 4(Yl144, YB; Y1201, YC; Y1226/7, YD; Y1253, YE) of the 5 sites. Strong Ras-dependent signalling was mediated through adaptors Grb-2 (YB) and SHC (YD). In contrast to biochemical evidence, a strong Ras component was not genetically detected for YC or YE. </p> <p> We have conducted two enhancer-suppressor screens to identify novel Ras and non-Ras requirements for YC signalling. For the first screen, a quantitative approach was designed to identify modification of an YC-specific wing notch phenotype. Thirty-two members of the Ras/MAPK signalling cassette were assessed. Sensitivity to Ras, Raf, MAPK and the Ras-related GTPase R-Ras was identified downstream ofYC. The second screen, a large-scale mutagenesis, took advantage of an YC-induced rough eye phenotype. From over 19 000 screened flies, 11 enhancers and 6 suppressors were isolated. One strong suppressor has been genetically mapped to the dual transcription factor and phosphatase eyes absent. Other promising Ras-dependent and Ras-independent modifiers await farther mapping. Results from both screens point to YC as a unique pTyr that uses both Ras-dependent and Ras-independent outputs. </p> / Thesis / Doctor of Philosophy (PhD)

Neu auftretende Viruskrankheiten zoonotischen Ursprungs stellen eine zunehmende Gefahr für die globale Gesundheit dar. Wie das unerwartete Auftreten von dem Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Ende 2019 zeigte, gibt es allerdings trotz jahrelanger intensiver Forschung Verständnislücken, wo und wann mit Tieren assoziierte Krankheitserreger auftauchen, oder durch welche evolutionären Vorgänge diese Übertragungen möglich werden. Diese Arbeit befasst sich mit dem Thema der genetischen Adaptation von Viren bevor und nachdem ein Wirtswechsel stattgefunden hat und leistet damit einen Beitrag zum besseren Verständnis von Wirtswechselprozessen und ihren zugrundeliegenden Mechanismen. / Emerging viral diseases of zoonotic origin pose an increasing threat to global health. Despite intense research, we do not understand where and when animal-associated pathogens emerge, or by what evolutionary processes these transmissions become possible; best illustrated by the unexpected emergence of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019. This thesis is concerned with the topic of viral genetic adaptation before and after cross-species transmissions, contributing to a better understanding of host switching processes and their underlying mechanisms.

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<p>From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade. </p><p>From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors.</p><p>Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.</p>

From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade. From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors. Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.

More than half of all cases of breast cancer occur among women without any known risk factors. More research is needed on suspected risk factors in order to refine current breast cancer screening tools. The objectives of this thesis were: to determine the breast cancer risk associated with known risk factors (ethnicity, family history, breast biopsy, age at menarche, age at first birth, alcohol, HRT, and BMI), suspected risk factors (smoking, second-hand smoke exposure, smoked/grilled foods, and NSAID use), and to examine the above associations according to tumour receptor status, histologic grade, and menopausal status, with potential confounders also considered. This thesis project was conducted within the framework of the Molecular Epidemiology of Breast Cancer study, a case-control study of women in Vancouver, BC and Kingston, ON, with 1140 cases and 1169 controls recruited from 2005-2010. Information was collected from a detailed questionnaire. Cases and controls were similar in terms of age at menarche, age at first birth, smoking history, second-hand smoke exposure, lifetime smoked/grilled food consumption, HRT, and BMI. Among cases, there were significantly less Europeans and more Chinese, Japanese, and Filipino subjects compared to controls. Cases were more likely to have a first degree relative with breast cancer, as well as a previous benign breast biopsy. Alcohol consumption and past NSAID usage was higher among controls. The level of education completed was higher among controls. Cases were also more likely to be postmenopausal. Family history was associated with breast cancer risk (OR=1.59, CI=1.30-1.94), as was BMI (OR=1.28, CI=1.05-1.58 for overweight and OR=2.28, CI=1.35-3.86 for obese class II). Second-hand smoke was also found to be associated with breast cancer risk (OR=1.42, CI=1.02-1.97 for individuals with a less than 10 pack-year smoking history). Due to reduced sample size with stratification and marginally significant results, it is not possible to draw definitive conclusions regarding pathology sub-types. In summary, these results provide support for the association between several risk factors and breast cancer risk. More research is needed to ascertain how receptor status, histologic grade, and menopausal status affect these associations. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-08-15 19:43:06.689