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Plant homeodomain finger protein 6 (PHF6) is a chromatin adaptor protein structurally defined by its two zinc-knuckle-atypical PHD (ZaP) domains. This structural configuration mediates its interaction with dsDNA, miRNA, the nucleosome remodeling and deacetylase (NuRD) complex and regulators of rDNA transcription (Upstream binding factor (UBF) and RNA polymerase-associated factor 1 complex (Paf1C)), ultimately facilitating its role as a chromatin adaptor protein and regulator of gene expression. Mutations in the gene are implicated in Börjeson–Forssman–Lehmann syndrome (BFLS), a rare X-linked intellectual disability disorder characterized by large ears, truncal obesity, and long tapering fingers. BFLS is primarily caused by missense and nonsense mutations while deletions, frameshifts and mutations disrupting the structural integrity of the ZaP domains have been described in T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) patients. To provide more insight into PHF6 and BFLS, we have generated a Phf6 transgenic mouse line with a patient-related nonsense mutation (R342X). We show that the mutation drastically reduced Phf6 transcript levels and produced a truncated protein at very low levels in the developing brain. Mice were born at normal Mendelian ratios but mutant mice were significantly smaller than control littermates. Volumetric analysis of the brain via high resolution MRI revealed increased sizes of the amygdala, periaqueductal gray, and hypothalamus, and decreased volumes within the striatum, hippocampus and cerebellum. Studies of the pituitary gland revealed a postnatal defect in the growth of the anterior pituitary but not the posterior or intermediate regions. This change was reflected in altered expression levels of several hormones in the hypothalamic-pituitary-adrenal axis. Preliminary behavioral tests highlighted deficits in the anxiety and depression response of the mutant mice. Additional studies to fully characterize these mice are ongoing.
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The Upper Niger Basins (UNB) and the Inner Niger Delta (IND) are integral parts of the Niger River Basin, which flows through 10 countries and constitutes the third longest river in Africa. Natural climate variability and human interventions are two major factors affecting the hydrological regime in the UNB and IND. This study focuses on the later factor, by assessing the hydrological impacts of key existing and planned manmade structures and irrigation schemes in the UNB: the Sélingué (existing dam in Mali), four variants of the Fomi/Moussako dam (planned in Guinea), and Office du Niger (irrigation scheme located in Mali). The Fomi /Moussako dam will be located in the headwaters of the UNB and therefore, is expected to alter the hydrological regime in large parts of the watershed. Expected impacts include a reduction of the flood peak which will adversely affect critical ecosystems in the IND, and higher flows directly downstream of the dams in the dry season to sustain irrigation. These higher flows will, however, be consumed by Office du Niger irrigation scheme, leading to possible severe water shortages downstream of the irrigation scheme and in the IND. This is likely to affect the Malian economy and the poorest parts of its population, as the IND is crucial for the socio-economic and ecological preservation and development of the population surrounding it. The hydrological impacts of the dams and the irrigation scheme were evaluated in this study by developing a model of the IND and UNB using SWAT (Soil and Water Assessment Tool). After the model was calibrated, the effects of the dams and the irrigation scheme on selected flow statistics (mean and standard deviation) were determined at fourteen hydrological stations. In general, the results have shown that (1) the Fomi/Moussako dam will noticeably reduce the downstream high flows, and reduce the average flow; (2) if the Fomi/Moussako dam was to be built, the alternatives with the least storage volume (Moussako 388.5') will have the least impacts on the downstream flows. To assist in related decision making for various users, a Decision Support System (DSS) was also developed. The goal of the DSS is to help users analyze the effects of dams and irrigation on the flow regime by performing a comparative analysis (presence and absence of dams and irrigation in the river). A number of potential adaptation measures were also proposed.
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Violence against Indigenous women is a major public health concern worldwide and Canada is no exception. Multiple forms of violence inform the broader context of violence against Indigenous women. Nurses are likely to encounter Indigenous women in a variety of settings, but evidence suggests that nurses may lack understandings of violence. This thesis explored the following question: How does extant qualitative research conducted in Canada, contribute to understanding the health and wellbeing of First Nations, Métis and Inuit (Indigenous) women who have experienced violence? During the development of this thesis, significant gaps were highlighted including underrepresentation of Inuit women in the literature, limited focus on health promotion, and lack of methodological approaches to systematic reviews that were participatory and inclusive of the community. Therefore, a secondary aim of this thesis was to privilege perspectives of Inuit women and their communities, by developing a study protocol for a collaborative and community centered approach to reviewing and assessing the extant literature. A configurative and inductive approach based on thematic synthesis was used to systematically search, retrieve, analyze and synthesize extant literature. Post-colonial feminist theory and intersectionality were used as theoretical lenses to emphasize intersections between multiple forms of violence and locate the problem within the broader context of colonization and oppression. Sixteen studies were included in this review, fifteen qualitative and one mixed methods study. Four themes with subthemes emerged based on analysis and synthesis of findings in the included studies: 1) ruptured connections between family and home, 2) that emptiness… my spirit being removed, 3) seeking help and feeling unheard, and 4) a core no one can touch. These themes represent interconnected pathways that influenced health among Indigenous women, and have implications for healthy public policy, clinical practice, and nursing education.
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Although the concept of fractional calculus was known for centuries, it was not considered in engineering due to the lack of implementation tools and acceptable performance of integer order models and control. However, recently, engineers and researchers started to investigate the potentially high performance of fractional calculus in various fields among which are acoustics, conservation of mass, diffusion equation and specifically in this thesis control theory. The intention of this thesis is to analyze the relative performance of fractional versus integer order PID controller for a quadcopter. Initially, the dynamics of the quadcopter is presented with additional consideration of the ground effect and torque saturation. Then, are introduced the concept of fractional calculus and the mathematical tools to be used for modeling fractional order controller. Finally, the performance of the fractional order controller is evaluated by comparing it to an integer order controller.
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Agriculturalists in Lebanon are exposed to a wide range of vulnerability factors that have direct impacts on farmers’ livelihoods. To evaluate the effects of those factors and the livelihood challenges they breed, this research analyses how two agricultural activities shape farmer livelihood vulnerability, namely urban agriculture and fruit and vegetable value chains. First, I analyze how vulnerability factors influence urban agriculturalist livelihoods and assess if urban agriculture is an adequate solution to lower their livelihood vulnerability. Second, I analyse how various actors partaking in fruit and vegetable value chains are exposed to different vulnerability factors and how this impacts their individual livelihoods. Conceptually, the urban agriculture component of this research builds from the vulnerability framework and sustainable livelihoods approaches scholarships. The agricultural value chain section engages with literatures centered on the vulnerability framework, sustainable livelihoods approaches and value chain analysis. This thesis concludes that the main vulnerability factors associated with urban agriculture relate to physical, financial and human capitals, and that urban agriculture is not an adequate tool to reduce the livelihood vulnerability of urban agriculturalists. I also conclude that social, financial and human capital barriers significantly affect agricultural value chains actors’ livelihoods. Overall, the vulnerability of the different actors is linked to their socioeconomic status, which dictates the amount of human capital they possess, thus their ability to adapt to changing conditions and external stressors. I posit that human capital is key to both urban agriculture and agricultural value chains, as this asset dictates the vulnerability of individual livelihoods and Lebanese agriculturalists’ ability to sustain their livelihoods.
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With the significant improvement in IoT technology and smart devices, data collection and distributed computation have led a foundation for Mobile crowd-sensing (MCS). MCS utilizes the capabilities of embedded sensors in smart devices for gathering data. MCS benefits both data provider (participant/user), and data requester, i.e. data providers via incentives/rewards, data requesters by delivering required data. Apart from the benefits gained through acquiring data, confronting challenges such as participant privacy, data trustworthiness, malicious attacks (from illegitimate users) need to be addressed to build robust and reliable data solicitation. In addition to that, it is necessary to consider user motivation and user preference, comfort during its engagement in crowd-sensing. User preferences/constraints can be due to privacy concerns in terms of location, the sensitivity of data or energy usage and many more. With this in mind, the main contributions of the thesis can be listed as follows. 1) We design user selective trustworthy data acquisition frameworks. We introduce a variety of user selection criteria to form participant communities based on participants reliability and income. To evaluate the trustworthiness of our selective reputation-based data acquisition, we consider malicious users in the environment and calculate the total rewards given to malicious users. Simulations results show that community formation based on the acquired income of participants ended up with a substantial loss to the cloud platform as well as participants. Contrary to that, reputation-based community formation has shown nearly equal platform utility (profit), negligible loss of user utility compared to benchmark Non-selective data acquisition with 7% malicious probability. 2) Moreover, we attempt to enable users to modify (allow/deny access to) their builtin sensor set according to their comfort levels. We formulate three comfort levels high (only allow access to sensors that would not directly reveal personal identity such as accelerometer, light sensor, etc.), moderate (obstruct access to sensitive data, e.g. camera), zero comfort (allow access to all users). We introduce Static modification, where users pre-arrange their sensor set before the start of data collection. Our feasibility study shows that pre-arrangement of the sensor set favours user comfort, user utility at the cost of loss in platform utility and performs better than selective reputation-based recruitment for the considered settings. 3) We apply Adaptive sensor modification on top of pre-arrangement of sensor set through which participants are authorized to re-arrange their sensor availability based on reliability scores. Simulation results show that the Adaptive comfort-aware approach performed better than static in terms of platform utility and achieved comparatively better user comfort with reasonable loss in user utility.
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This dissertation focuses on the works of Henry David Thoreau, Invisible Man by Ralph Ellison, and a wide variety of Jonathan Lethem’s stories. Situating my argument within the nascent field of solitude studies, I argue that solitude has so far been incorrectly defined. It is not loneliness, not alienation or isolation, disenfranchisement, ennui or detachment. I say that solitude is harder to define, and I go further to claim that attempts to define solitude are doomed to fail because of the very nature of solitary practice. Solitude is a praxis through which these authors resist various totalizing narratives that seek to delimit or control bodies. I suggest that solitude as we know it owes its life to Thoreau, but that our understanding of Thoreau’s solitude has been coloured by misinterpretations or misattributions. The hermit’s teachings reject the idea that solitude can be defined by space, time, or friendship. Solitude can be inhibited or promoted by these states, but it is never singularly caused by them. Solitary practice exists on the threshold. Thoreau as a writer had boots on the ground during the beginnings of the industrialization of the American prison system we know today; the insights he was able to glean from seeing firsthand the development of solitary confinement are especially relevant to our encounter with contemporary America. Almost all critics agree that a study of solitude must begin with Thoreau, but almost all of them immediately lose sight of the three main things Thoreau was attempting to do: resist historical hegemony, refuse ‘progress’ a voice, and remind people that however political a discussion, real bodies and real people were victims. Several important contexts inform this study, but the main discussion touches on issues surrounding gentrification, incarceration, trauma and loss, and how writing confronts the unimaginable. In each section of this dissertation I emphasize especially the ontological dimension of solitude—its undeniable body—and the way writing itself can be used to disrupt or confront narrative hegemonies that seek to control or limit. I examine Thoreau’s idea of the threshold, his development of a theory of solitary practice, Ellison’s conscription of solitude as a mode of resistance against dispossessive narratives of historical progress, and Lethem’s beautifully haunting commentaries on individual and national trauma. I situate my discussion of solitude against a number of exigent contemporary issues, especially trauma and prisonhood. The American obsession with incarceration creates and perpetuates traumas both individual and national. I map Thoreauvian solitude against the modernist anti-historicist novel Invisible Man and conclude the discussion by seeing how Jonathan Lethem’s novels, especially those written after 9/11, can further explain and expand our understanding of contemporary solitudes. My argument is not developmental or chronological, other than for convenience. My purpose is not to show that things change over time; however, I do demonstrate the continuities of solitude across the past two centuries. Instead, I am engaged by the idea that solitude is a useful and versatile framework for understanding how authors might resist the prisonization or supermaxing of American culture. These authors, disparate as they might be, are all fascinated by solitude. I ask a series of questions I believe have been overlooked in contemporary Americanist studies of solitude: what happens to solitary bodies; what is going on with incarceration in America; how does solitude help us understand trauma; how does solitude affect writing?
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Despite the rich knowledge surrounding risk factors for malaria, the spatial processes of malaria transmission and vector control interventions are underexplored. This thesis aims 1) to describe the spatial variation of risk factor effects on malaria infection, and 2) to determine the presence and range of any community effect from malaria vector control interventions. Data from a cluster-randomized control trial in Tanzania were analyzed to determine the geographically-weighted odds of malaria infection in children at trial baseline and post-intervention. The spatial range of intervention effects on malaria infection was estimated post-intervention using semivariance models. Spatial heterogeneities in malaria infection and each covariate under study were found. The median effective semivariance range of intervention effects was approximately 1200 meters, suggesting the presence of a community effect that may cause contamination between trial clusters. Trials should consider these spatial effects when examining interventions and ensure that clusters are adequately insulated from contamination.
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Dans le cadre de cette thèse, nous nous intéressons aux représentations de la sorcière dans la littérature d’inspiration historique à partir des années 1970. Nous analysons la construction de cette figure protéiforme et les métamorphoses qu’elle connaît dans l’imaginaire social lors des dernières décennies du XXe siècle. Plus précisément, nous examinons les différentes facettes de la sorcière, telles qu’elles apparaissent dans quatre romans francophones d’inspiration historique, en relation avec les discours historiques, féministes et postcoloniaux, et les autres productions culturelles de la même période. En étudiant les interactions entre les représentations de la sorcière et d’autres œuvres, travaux et tendances de l’époque, notre thèse met en lumière les problématiques abordées à travers cette figure dans les textes littéraires. La figure de la sorcière reprend notamment des enjeux qui marquent les dernières décennies du XXe siècle, tels la place des femmes et des cultures minoritaires dans la société, la représentation du corps féminin, le recul des religions traditionnelles et l’écriture de l’Histoire. Au moyen des approches sociocritique et intertextuelle, nous explorons ces enjeux et analysons la façon dont les œuvres développent ou prolongent ces réflexions en abordant la figure de la sorcière. De manière à pouvoir tracer l’évolution de la figure et des questions qui lui sont liées, la thèse est divisée en trois parties, représentant chacune une décennie distincte. Après un préambule brossant un tableau de l’imaginaire de la sorcière au début des années 1970, une première partie se concentre sur la construction de la figure de la sorcière dans les romans Les Enfants du sabbat d’Anne Hébert et La Fontaine obscure de Raymond Jean, parus lors de la décennie 1970. Une deuxième partie, centrée sur la décennie 1980, se penche sur le roman Moi, Tituba sorcière... de Maryse Condé. Enfin, une troisième partie s’intéresse au roman Instruments des ténèbres de Nancy Huston, publié pendant les années 1990. En combinant différentes approches, cette thèse tend à mieux comprendre la fonction de la sorcière dans la littérature et les idées qui lui sont associées dans l’imaginaire social à partir de 1970.
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Broadly speaking, the work herein discussed encompasses the development of biomolecular assays for biomarker detection. Specific to the assays in this thesis is the design of reaction schemes that consider the unique requirements of one class of single-molecule sensors in particular: solid-state nanopores formed using a novel fabrication and conditioning technique discovered during this research at the University of Ottawa. We present three unique assays for the detection of different biomolecular targets. The first uses a class of DNA origami structures termed nanoswitches to translate the presence of a short segment of single-stranded DNA Zika virus biomarker to a large configurational change in a double-stranded DNA scaffold. The signal amplification inherent in this topological change allowed us to a achieve a high degree of specificity for detecting a small nucleic acid target by requiring two separate binding events. Furthermore, through careful design of the configurational change, the number of topological states that a solid-state nanopore can sense is limited, providing unambiguous signals in ionic current recordings. Quantification of the Zika gene was performed by sensing the relative amounts of nanoswitches in looped and linear configurations from only hundreds of individual molecules. We then explored the sensitivity of solid-state nanopores for detecting small molecular features along short DNA scaffolds. Leveraging the ability of our nanopores to detect the presence of these protrusions, we present results in which ATP, a molecule significantly too small to be directly detected by the nanopore sensor, initiated an aptamer-based DNA displacement reaction to form a protrusion along scaffolds, producing measurable changes in ionic current signatures in nanopore recordings. Finally, we present an assay in which a microRNA, a biomarker linked to various cancers, was detected through the conjugation of two probes, each of which contained a binding site to different segments of the microRNA. In addition to examining different probe set structures for optimal performance, our two-probe design aimed to improve specificity over conventional single-probe-based assays which only require one recognition step, while still providing unambiguous signals due to the greater-than-doubling in molecular complex size upon conjugation. Furthermore, the use of two individual small probes, rather than one large nanoswitch, increased the resolution with which we could differentiate microRNA concentrations. The assay enabled the quantification of six concentrations of microRNA spanning a single order of magnitude, in only several hundred events, and allowed us to take advantage of the reduced cost, material and labour, as well as increased nanopore capture rates, associated with small assembled molecules.
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