Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In a genomic scan two chromosomal regions with evidence for linkage was observed. The strongest support was found on chromosome 19p with an allele sharing LOD score of 2.91 (genome-wide P = 0.032). The second region, showing suggestive evidence of linkage, was observed in the centromeric region of chromosome 5. Linkage analyses of densely spaced markers on chromosome 8p22-23 confirmed (P = 0.03) previously reported linkage to this region. A systematic evaluation of the possible impact that the RNASEL gene have on prostate cancer was performed. Overall, limited evidence for association with prostate cancer risk was found. The results provide strong evidence against a role of RNASEL in prostate cancer etiology in Sweden. In a comprehensive evaluation of occurrence of other malignancies in HPC families, previously reported association between gastric and prostate carcinoma was confirmed. The increased risk was of the same magnitude in early and late onset HPC families and confined to only male relatives. A genome-wide linkage analysis, stratified by occurrence of gastric carcinoma, identified a novel susceptibility locus on chromosome Xp21. In summary, chromosome 5q and 19p represents the regions most likely to harbor susceptibility genes predisposing to prostate cancer in the Swedish population. A common genetic basis for both gastric and prostate cancer has been confirmed and a novel susceptibility locus on chromosome Xp21 has been identified.

Stimulation or repression of gene expression by genome-wide regulatory mechanisms is an important epigenetic regulatory function which can act to efficiently regulate larger regions or specific groups of genes, for example by compensating for loss or gain of chromosome copy numbers. In Drosophila melanogaster there are two known chromosome-wide regulatory systems; the MSL complex, which mediates dosage compensation of the single male X-chromosome and POF, which stimulates expression from the heterochromatic 4th chromosome. POF also interacts with the heterochromatin inducing protein HP1a, which represses expression from the 4th chromosome but which also has been assigned stimulatory functions. In addition to these two, there is another more elusive and less well-characterized genome-wide mechanism called buffering, which can act to balance transcriptional output of aneuploidy regions of the genome (i.e. copy number variation). In my thesis, I describe the presence of a novel physical link between dosage compensation and heterochromatin; mediate by two female-specific POF binding sites, proximal to roX1 and roX2 on the X chromosome (the two non-coding RNAs in the MSL complex). These sites can also provide clues to the mechanisms behind targeting of chromosome-specific proteins. Furthermore, to clarify the conflicting reports about the function of HP1a, I have suggested a mechanism in which HP1a has adopted its function to different genomic locations and gene types. Different binding mechanisms to the promoter vs. the exon of genes allows HP1a to adopt opposite functions; at the promoter, HP1a binding opens up the chromatin structure and stimulates gene expression, whereas the binding to exons condense the chromatin and thus, represses expression. This also causes long genes to be more bound and repressed by HP1a. Moreover, I show that buffering of monosomic regions is a weak but significant response to loss of chromosomal copy numbers, and that this is mediated via a general mechanism which mainly acts on differentially expressed genes, where the effect becomes stronger for long genes. I also show that POF is the factor which compensates for copy number loss of chromosome 4.

Structural steel design standards recognize lateral torsional buckling as a failure mode governing the capacity of long span unsupported beams with wide flange cross-sections. Standard solutions start with the closed form solution of the Vlasov thin-walled beam theory for the case of a simply supported beam under uniform moments, and modify the solution to accommodate various moment distributions through moment gradient expressions. The Vlasov theory solution is based on the assumption that cross-sectional distortional effects have a negligible effect on the predicted elastic critical moment. The present study systematically examines the validity of the Vlasov assumption related to cross-section distortion through a parametric study. A series of elastic shell finite element eigen-value buckling analyses is conducted on simply supported beams subject to uniform moments, linear moments and mid span point loads as well as cantilevers subject to top flange loading acting at the tip. Cross-sectional dimensions are selected to represent structural steel cross-section geometries used in practice. Particular attention is paid to model end connection details commonly used in practice involving moment connections with two pairs of stiffeners, simply supported ends with a pair of transverse stiffeners, simply supported ends with cleat angle details, and built in fixation at cantilever roots. The critical moments obtained from the FEA are compared to those based on conventional critical moment equations in various Standards and published solutions. The effects of web slenderness, flange slenderness, web height to flange width ratio, and span to height ratios on the critical moment ratio are systematically quantified. For some combinations of section geometries and connection details, it is shown that present solutions derived from the Vlasov theory can overestimate the lateral torsional buckling resistance for beams.

The strain on modern electrical power systems has led to an ever-increasing utilization of new information and communication technologies (ICT) to improve their efficiency and reliability. Wide area monitoring and control (WAMC) systems offer many opportunities to improve the real-time situational awareness in the power system. These systems are essen-tially SCADA systems but with continuous streaming of measurement data from the power system. The quality of WAMC systems and the applications running on top of them are heavily, but not exclusively, dependent on the underlying non-functional quality of the ICT systems. From an ICT perspective, the real-time nature of WAMC systems makes them susceptible to variations in the quality of the supporting ICT systems. The non-functional qualities studied as part of this research are performance, interoperability and cyber security. To analyze the performance of WAMC ICT systems, WAMC applications were identified, and their requirements were elicited. Furthermore, simulation models capturing typical utility communication infrastructure architectures were implemented. The simulation studies were carried out to identify and characterize the latency in these systems and its impact on data quality in terms of the data loss. While performance is a major and desirable quality, other non-functional qualities such as interoperability and cyber security have a significant impact on the usefulness of the sys-tem. To analyze these non-functional qualities, an enterprise architecture (EA) based framework for the modeling and analysis of interoperability and cyber security, specialized for WAMC systems, is proposed. The framework also captures the impact of cyber security on the interoperability of WAMC systems. Finally, a prototype WAMC system was imple-mented to allow the validation of the proposed EA based framework. The prototype is based on existing and adopted open-source frameworks and libraries. The research described in this thesis makes several contributions. The work is a systematic approach for the analysis of the non-functional quality of WAMC ICT systems as a basis for establishing the suitability of ICT system architectures to support WAMC applications. This analysis is accomplished by first analyzing the impact of communication architectures for WAMC systems on the latency. Second, the impact of these latencies on the data quali-ty, specifically data currency (end to end delay of the phasor measurements) and data in-completeness (i.e., the percentage of phasor measurements lost in the communication), is analyzed. The research also provides a framework for interoperability and cyber security analysis based on a probabilistic Monte Carlo enterprise architecture method. Additionally, the framework captures the possible impact of cyber security on the interoperability of WAMC data flows. A final result of the research is a test bed where WAMC applications can be deployed and ICT architectures tested in a controlled but realistic environment. / <p>QC 20130218</p>

International regulations target a global reduction of carbon dioxide (CO2) emissions through the allocation of national reduction targets and the definition of mechanisms to achieve these targets. One of these mechanisms is international emissions trading, these trading programs have been the targets of widespread criticism since they were introduced into the policy-making arena. The point of departure in this study has been that the trading raises questions about morality, since it implies signals, which legitimates pollution. The main purpose with this study has been to find out if emissions trading systems can be morally justified with the method of wide reflective equilibrium. From the study it was found that the moral intuition; it is wrong to pollute the environment, and perform activities, which legitimates pollution, finds support from the different theories within environmental ethics and Kantian ethics. But, it was also found that there are a number of background theories, such as neo-classical economic thinking, liberalism, and utilitarianism, that supports the notion of emissions trading. The paper argues that even though the concept of CO2-emissions trading raises moral questions it can be morally defended on the basis of rationality. When the theory about specification is applied to the concept of emissions trading it is possible to reach a situation were a wide reflective equilibrium is achieved.

Collaborative tagging is a simple and effective method for organizing and sharing web resources using human created metadata. It has arisen out of the need for an efficient method of personal organization, as the number of digital resources in everyday lives increases. While tagging has become a proven organization scheme through its popularity and widespread use on the Web, little is known about its implications and how it may effectively be applied in different situations. This is due to the fact that tagging has evolved through several iterations of use on social software websites, rather than through a scientific or an engineering design process. The research presented in this thesis, through investigations in the domain of e-learning, seeks to understand more about the scientific nature of collaborative tagging through a number of human subject studies. While broad in scope, touching on issues in human computer interaction, knowledge representation, Web system architecture, e-learning, metadata, and information visualization, this thesis focuses on how collaborative tagging can supplement the growing metadata requirements of e-learning. I conclude by looking at how the findings may be used in future research, through using information based in the emergent social networks of social software, to automatically adapt to the needs of individual users.

The objective of this research is to demonstrate the feasibility of the implementation of wideband RF CMOS PLLs with high spectral purity using deep sub-micron technologies. To achieve wide frequency coverage, this dissertation proposed a 45-nm SOI-CMOS RF PLL with a wide frequency range to support multiple standards. The PLL has small parasitic capacitance with the help of a SOI technology, increasing the frequency tuning range of a capacitor bank. A designed and fabricated chip demonstrates the PLL supporting almost all cellular standards with a single PLL. This dissertation also proposed a third order sample-hold loop filter with two MOS switches for high spectral purity. Sample-hold operation improves in-band and out-of-band phase noise performance simultaneously in RF PLLs. By controlling the size of the MOS switches and control time, the nonideal effects of the MOS switches are minimized. The sample-hold loop filter is implemented within a 45-nm RF PLL and the performance is evaluated. Thus, this research provides a solution for wideband CMOS frequency synthesizers for multi-band, multi-mode, and multiple-standard applications in deep sub-micron technologies.

En donnant accès à la théorie de la géométrie projective sous l'angle des médias interactifs, le projet Perspective théâtrale sur la géométrie projective permet une expérience unique d'apprentissage et de communication en ligne. De la formulation des objectifs à la maquette, il a fallu s'approprier les contenus, les catégoriser, les diviser, les relier, les structurer. Ce mémoire fait état de la démarche de structuration des ressources médiatisées d'un cours de géométrie projective et d'une pièce de théâtre sur la vie du mathématicien créateur de cette théorie, puis de la diffusion de ces contenus sur la Toile, par baladodiffusion ou en mode présentiel, en ayant recours au Web collaboratif et sémantique. Ces nouveaux contextes d'échange permettent de passer outre les contraintes de distance, de temps et de disponibilités des personnes intéressées, tout en transmettant des informations à jour sur un sujet et en faisant participer activement les utilisateurs à façonner et partager leur expérience d'apprentissage. L'information sémantique attachée à chacune des unités médiatiques permet une appropriation des contenus sous de multiples facettes: linéairement, constructivement, artistiquement. Une ontologie ajoute une enveloppe conjonctive aux contenus, donnant une structure de navigation cohérente. Cette ontologie permet à la fois de gérer les différentes ressources multimédias du projet, de construire le portail les diffusant et d'offrir aux usagers des interfaces interactives pour les manipuler. Des créateurs aux usagers, tous manipulent et profitent de la structure de l'ontologie et des ressources qui la composent. Brain Cuts, un éditeur de courts métrages, est un exemple d'outil permettant aux usagers d'agréger eux-mêmes les ressources multimédias du cours. Les nouveaux outils qu'apporte l'avènement du Web sémantique aideront peut-être à construire un écosystème de connaissances (Knowledge Ecosystem) sur la Toile. Ce projet sert de plateforme expérimentale à ces nouveaux moyens interactifs en éducation. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Médias interactifs, Toile, Web, Web sémantique, Ontologie, Téléapprentissage, Théâtre, Mathématiques, Géométrie projective, Gestion des connaissances.

Ce mémoire traite de cette question : qu'ont en commun sacré et communication? Rien à priori ne permet de penser qu'ils entretiennent un rapport de parenté, ni même de résonance. Pourtant, les moyens de communication véhiculent des idéologies, ces manières de penser le monde qui s'imposent comme seules légitimes. Or, ces modes de communication agissent eux-mêmes selon des paramètres précis qui orientent les manières de recevoir et d'émettre. C'est qu'ils sont aussi représentatifs des valeurs culturelles, des désirs et craintes des individus. Plus spécifiquement, la tendance consensuelle actuelle tend à penser Internet comme un formidable outil de démocratisation de l'information et de ce fait, laisse peu de place au doute. Ce discours dominant semble symptomatique d'une adhésion aveugle à un système auquel on voue un véritable culte qui serait, du coup, sacralisé. Qu'est-ce alors que le sacré et le processus de sacralisation? Le premier chapitre s'emploie à relier les définitions d'auteurs permettant de dégager des traits prégnants du sacré et de le distinguer du religieux. De cette base conceptuelle émane le constat qu'il y aurait un besoin primordial de sacré à la fois riche et complexe. Ainsi, que les traces du sacré se lisent aisément dans les ordres spirituels, moraux, imaginaires, politiques et dans les questions qui mobilisent l'humain, l'humanité et ce, individuellement et collectivement. Au deuxième chapitre, le Web est directement mis en cause et à contribution. C'est alors qu'une parenté entre certaines caractéristiques d'Internet, d'une part, et du religieux, d'autre part, sert de levier à une compréhension accrue des phénomènes de ritualisation et de sacralisation. Ainsi les outils et usages induits renvoient constamment à une désacralisation-sacralisation, processus qui éclaire certains paradoxes, non sans incidence sur les enjeux sociaux, politiques et économiques. Parmi ceux-ci, le sacrifice peut participer à rendre sacrés les us et conventions. Conséquemment, le troisième chapitre adopte un point de vue sociopolitique qui met en relief l'instrumentalisation du Web à des fins politiques de même que les responsabilités incombant aux individus qui, par ailleurs, jouent un rôle majeur dans l'évolution des communications. Par là, dans le quatrième chapitre, sont explorées les voies d'évitement consenties et souhaitables dans le contexte actuel (mondialisation, multiculturalisme, éclatement des pratiques). Et ce, en déconstruisant le sacré véhiculé à travers ce que communiquent les questions environnementales, la postmodernité, le déclin des humanités dans l'enseignement, et enfin en illustrant quelques cas tangibles de transgression. De cet ensemble se dégagent certains grands thèmes du sacré, à même la religiosité fanatique patente d'Internet. Loin de nous être étranger, le sacré en matière de communication est à l'œuvre, dans ses variations et déviations, autant dans un registre familier que dans ce qui peut déterminer la condition humaine. À partir de ce constat, le désir de mouvement collectif et les aspirations individuelles ne peuvent qu'être réitérés par les quêtes d'éléments qui nous approchent d'un sacré parfois paradoxal mais semble-t-il, toujours essentiel. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Sacré, communication, Web, Internet, religieux, mythe, sacralisation, désacralisation, vie privée, humanité, politique, société.

A multi-period optimal energy planning program for Ontario has been developed in mixed-integer non-linear programming using General Algebraic Modeling System, GAMS. The program applies both time-dependent and time-independent constraints. These include, but not limited to, construction time, fluctuation of fuel prices, and CO2 emission reduction target. It also offer flexibility of fuel balancing and fuel switching of the existing boilers and option purchasing of Carbon credit if the reduction target is not achievable. The objective function incorporates all these constraints as well as minimizes over all the cost of electricity and meets the projected electricity demand over the 30 years horizon. A number of Ontario study cases are performed utilizing this 30 years model. These cases include a number of CO2 emission reduction target from 6% to 75% below that of 1990 levels by 2014, doubling of natural gas over the forecasted price in 2020, an arbitrary year. A study case in appliance with the Environmental Protection Act where no new or existing coal-fired power stations are available after 2014, as well as study cases where no new nuclear power stations are available. The overall cost of the electricity for different CO2 emission reduction targets increases linearly with slope of ~ 5. The fuel switching, fuel balancing for coal stations, and retrofitting of the carbon capture and storage are the main strategy in order to keep the cost of electricity relative low and satisfy the CO2 emission constraints. Nuclear power is an essential supply technology to the fleet especially when CO2 emission is concerned. An additional 248 Mt of CO2 emission is observed over the reference case when no new nuclear supply is offered. Eliminating all coal technologies by 2014 in accordance to the Environmental Protection Act may also reduce the CO2 emission with less additional expenditure normally associated with the emission reduction processes. This however also reduces the energy port folio diversity, forcing the system to depend on a smaller group of supply technologies and decreasing the reliability of the system overall. These results help us better understand the factors affecting the fleet’s structure. It may also help plan the energy direction of Ontario and perhaps serve as an example for other provinces, territories, states, and even countries.