<p>The disease process giving rise to cancer involves the consecutive accumulation of genetic or genomic alterations impacting the normal regulation of cellular functions. In cases of hereditary cancers, this process may be stepwise, with a shared initiating lesion leading to common subsequent alterations. However, in many non-hereditary forms of cancer the initiating and subsequent alterations giving rise to the tumor can vary substantially from individual to individual, and multiple molecularly distinct subsets of the disease can exist within histopathologically similar tumors. This molecular heterogeneity between patients hinders the ability to identify which alterations are responsible for tumor development and subsequent maintenance, and confounds the ability to effectively treat patients as response to a particular therapeutic intervention may be highly dependent on the molecular composition of the disease.</p><p>To further our understanding of the molecular alterations associated with tumorigenesis, we analyzed aggressive brain cancer, glioblastoma (GBM), samples for which multiple types of genome-wide information was available. We utilized a series of in vitro or clinically derived gene expression signatures by comparing gene expression of samples based on whether a particular cellular signaling pathway was known to be active or inactive. Using these signatures for cellular signaling deregulation, we examined the association between various genomic alterations and the relative activity of each pathway, identifying alterations that were enriched within patients that harbored similar profiles of pathway activation. These analyses lead to the identification of numerous previously uncharacterized alterations in GBM, including the identification of a ubiquitin-like gene, UBL3, that was associated not only with pathway signaling, but was also associated with poor patient outcome, as well as response of GBM xenograft models to treatment with standard of care therapeutic agents.</p><p>Further, given that the challenges involved in analyzing clinical samples include development methods for timely analysis of genomic data, we have described a framework to utilize these genomic signatures in a prospective setting by incorporating a non-overlapping reference dataset of similar tumor samples. This methodology allows the examination of pathway signaling, as captured by the signature, to be run in real-time when only a single patient sample is analyzed, and has a high degree of fidelity to the results generated from retrospective analysis across multiple tumor types. Together these studies have provided a novel framework for identification of significant genomic alterations that impact pathway signaling, as well as moving providing the mechanisms to analyze genomic signatures in a robust manner that accounts for the challenges associated with the prospective clinical setting.</p> / Dissertation

Masters of Commerce / Despite having a significant agri-food sector, South Africa is faced with strong food security issues related to high inequalities and the legacy of the apartheid regime. The South African food system finds itself at risk of alienating the majority of its citizens from realizing their right to access food granted by the South African Constitution (1996) Section 27(1)(b). Increasing poverty, unemployment and poor governance are making it harder for ordinary South African citizens to put safe and nutritious food on the table. Part of the food security issue in South Africa is that there is an inefficiency in public policies. It can be explained by the extreme segmentation of public action between departments and also by the limitations and ineffectiveness of decentralization resulting in little to no involvement from local governments. Like most socio-economic issues, the effects of food insecurity are first experienced on the ground at the local level where municipalities are at the forefront. The absence of effective policy around food security and food systems at the local level in South Africa leaves room for research on improved local food governance. Municipalities should be best suited to understand the consequences of food insecurity and could therefore use some of their constitutional mandate which provides some room for manoeuvre with regard to food issues. The aim of this study is to raise awareness of food security issues at the municipal level and to identify ways to facilitate engagement by municipalities. Its main objective was to adopt a foresight approach, using scenarios with local actors, and to understand how it can help improve the engagement of municipalities and citizens in the food security debate and take possible action. This research has made use of an existing collaboration between the Centre of Excellence in Food Security (CoE-FS) and the South African Local Government Association (SALGA) developed in the Western Cape. The collaboration focuses on the understanding of the food policy space in South Africa, the results of existing policies, and how the co-production of knowledge between stakeholders, notably at the local level, can contribute to policy improvement.

Le marché des systèmes photovoltaïques a connu une forte croissance cette dernière décennie soutenue par des actions politiques favorables dans un contexte de transition énergétique. Pourtant, malgré ces conditions bénéfiques, le marché mondial du PV a paradoxalement traversé une période chaotique rencontrant des problèmes de surproduction, une crise industrielle et des différends commerciaux durable entre pays. Cette thèse part de ces problématiques et tente de comprendre les politiques publiques PV et les impacts sur la dynamique des technologies et des marchés. Afin de préciser ces questions, une approche systémique est utilisée pour fournir une compréhension correcte des mécanismes généraux des politiques publiques PV. Une vue d’ensemble systémique concrète de ces mécanismes est construite sur la base d’analyses théoriques et historiques en définissant les variables clés et le contexte. Une analyse rétrospective utilisant des mappings construits pour l’occasion est conduite afin de cerner les limites et défis critiques du secteur PV ainsi que les facteurs de risque. Cette thèse montre également la façon dont la nature du contexte politique change en liaison avec la dynamique du secteur PV. La thèse met en évidence que la dynamique nationale a été brisée par l’entrée de la Chine sur le secteur PV. La thèse propose au final des orientations stratégiques pour le développement du PV selon deux dimensions, nationale et internationale. Au niveau national, la thèse s’intéresse à l’autoconsommation PV en tant que manière naturelle d’utiliser l’énergie PV dans le système électrique. Cette analyse implique un changement de nature des politiques PV dans le futur. Pour terminer, afin de résoudre la crise industrielle actuelle, la thèse présente des possibilités d’actions internationales en collaboration pour créer une nouvelle demande PV dans le contexte international en recherchant des bénéfices économiques et environnementaux au niveau mondial. / Solar PV systems have experienced strong market growth over the last decade supported by favorable political reactions in the energy transition context. However, despite these favorable conditions, paradoxically, the global PV market recently went through a chaotic time encountering the overproduction issue, the industry crisis and the long-lasting trade disputes. This thesis started from these problematics to understand the PV public policies and the impacts on dynamics of technology systems and markets. In order to define those issues, a systemic approach is taken to provide an accurate comprehension of the overall mechanisms of PV public policies. The concrete systemic vision of PV policy mechanisms is constructed based on theoretical and historical analysis by defining key variables and the context. A retrospective analysis using the proposed mapping tools is conducted to understand critical limits and challenges of PV development and to identify risks factors in the sector. This thesis also demonstrates how the nature of policy context changes in combined with the dynamic feature of the PV sector. Our analysis highlights the nationwide PV policy dynamics was broken with the arrival of China in the PV sector. This thesis eventually proposes strategic orientations of PV development at the two dimensions from both national and international perspectives. At the national level, this thesis discusses on PV self-consumption as the natural way of PV power use in the electricity system. This analysis implies a change in the nature of PV policies in the future. Next, as a response to the current global industry crisis, the thesis proposes opportunities of international collaborative actions to create new PV demand in the international context in pursuit of global economic and environmental benefits.