VictorJuiz/thesis huggingface dataset:
Metabolic Feedback Control through H3K4 Demethylation
Keywords: Chromatin
Epigenetics
Histone demethylation
JARID1
Metabolism
Mitochondria

There are many known pathways by which gene expression responds to the environment. Signaling through transcription factors and chromatin modifiers is well established for regulating cell development, differentiation and cellular identity. In this thesis I describe an additional layer of regulation – a metabolic one. I find that perturbations in the steady state levels of a particular metabolite are associated with measurable changes in the activity of a chromatin modifying enzyme and lead to alterations in gene expression. Specifically, demethylation of histone H3 on lysine 4 (H3K4) by the evolutionarily conserved JARID1 family protein, Jhd2, can respond to the intermediary metabolite α-ketoglutarate (αKG). Under respiring growth conditions, wherein production of αKG increases, Jhd2-mediated regulation orchestrates a transcriptional response that then represses mitochondrial respiration in a homeostatic manner. Further characterization of the sole budding yeast homolog, Jhd2, reveals that the demethylase responds to mitochondrially or nutritionally derived αKG to accomplish global H3K4me3 demethylation and repression of mitochondrial respiration on a transcriptional and physiological level, specifically by controlling the tricarboxylic acid (TCA) cycle and electron transport chain (ETC). In concordance with several studies that have previously established a role for mitochondrial respiration in regulation of lifespan in varied organisms, I find that Jhd2 limits yeast replicative lifespan and respiratory growth. In contrast to the limited role of H3K4 demethylation under standard fermenting conditions, I describe additional roles for Jhd2 in regulating transcriptional and metabolic quiescence during the cell differentiation program of yeast gametogenesis, also known as sporulation. The contexts of increased cellular respiration and yeast sporulation represent physiological scenarios of S. cerevisiae alternative to the more typically investigated highly proliferative fermentative cells. The role of H3K4me dynamics and, specifically, of the JARID1 family is well established for its involvement in cellular differentiation and oncogenesis in animal models and humans by yet uncharacterized mechanisms. The work described herein sheds light on the function of JARID1 demethylases and illuminates their central role in regulating mitochondrial respiration in response to differentiation cues. These findings provide insights into candidate mechanisms by which JARID1 enzymes may regulate cellular physiology in humans and impact oncogenesis.
Science-Market Analogies: A Philosophical Examination
Keywords: economic epistemology
economics of science
social epistemology

Many philosophers have made analogies between science and the market, or between scientists and entrepreneurs. These analogies are used to buttress claims about how science ought to be organized: that science ought to be administered or regulated, or that science must be autonomous. This dissertation examines and evaluates market analogies, and ways in which the changing organization of science reflects those analogies. In the first chapter I examine Michael Polanyi's dispute with John Desmond Bernal over whether science ought to be centrally controlled, and I argue that Polanyi's account of spontaneous order in science fails. In the second I compare Philip Kitcher's model of scientist-entrepreneurs with the general equilibrium model of Arrow and Debreu and conclude that Kitcher's model lacks crucial features of the latter. In the third chapter I examine Alan Walstad's Austrian account of science and argue that his analogy fails because citations fail to fulfill all of the important functions of money in the traditional economy. In the fourth chapter I evaluate science from the perspective of the Efficient Market Hypothesis (EMH) and conclude that science is not epistemically efficient in the way that the EMH claims markets are, and then I examine ways in which science might be made more epistemically efficient through the use of prediction markets. In the final chapter I consider how, through commodification, science is becoming more like the market, and I show that this change in the organization of science allows for increased scientific collaboration, but also facilitates the commercialization of science and all of its associated dangers.
Molecular Determinants of Metastasis in Pediatric Cancers
Keywords: Drug Discovery
Gene Expression
Metastasis
Neuroblastoma
Osteosarcoma
Signaling

Metastasis is the spread of cancer cells from the primary site to other organs in the body. Although metastasis is responsible for 90% of all cancer-related deaths, the molecular mechanisms involved and tools to study metastasis are not well established in pediatric solid tumours. Two such tumours are osteosarcoma (OS) and neuroblastoma (NB), in which metastatic disease predicts poor survival (
Heterogeneous Runtime Support for Partitioned Global Address Space Programming on FPGAs
Keywords: Accelerators
FPGAs
Heterogeneous
Parallel Computing
PGAS

We are presenting THeGASNet, a framework to provide remote memory communication and synchronization in heterogeneous, distributed systems composed of software components and FPGA components. It is intended as a runtime layer to support higher-level languages and libraries that implement the Partitioned Global Address Space(PGAS) model. PGAS is a shared memory parallel programming model intended for high-productivity programming of distributed, cluster-like systems. THeGASNet provides a communication abstraction with a common API for both software and hardware components, thereby facilitating easier migration of performance-critical application portions to reconfigurable computing hardware. To demonstrate the development flow, we have implemented three applications representing common distributed application characteristics, starting with software-only solutions and using the common API to efficiently move selected parts into FPGA hardware. Based on the accumulated experience, we illustrate why PGAS is a good model to program heterogeneous systems using FPGAs, define minimum infrastructure requirements and outline a vision for continued exploration of heterogeneous PGAS programming.
Crisis Foster Care in an Age of HIV and AIDS: Experiences of the Queen Mothers of Manya Klo, Ghana
Keywords: Medical Anthropology

Older women in communities ravaged by HIV and AIDS in sub-Saharan Africa have been hailed as constituting the most effective response to the growing number of orphans, which has overwhelmed the customary mechanisms of support. Over 80 percent of orphans in Ghana are fostered by women, because an orphan’s kinship networks - and particularly the female members of the networks - are expected to assume responsibility for her/him. Unfortunately, in the Manya Klo Traditional Area of Ghana, AIDS, poverty and other factors have weakened kinship support and cooperation, resulting in patchy external responses to physically frail and economically disempowered traditional female leaders (queen mothers) acting as caregivers. Most of the existing research about orphan care has focused exclusively on the woman-child dyad, thereby obscuring other forms of care. In particular, the “grandmother-led household” has become a self-fulfilling truism that has blinded researchers to other relationships of care. Moreover, the analyses of the situation of orphans are based on frameworks that ignore orphans' perspectives and the social context in which fostering is negotiated. In this study, I employ mixed methods to analyze an orphan care project run by the Manya Krobo Queen Mothers Association (MKQMA) and address three issues: (1) What is the socio-economic and cultural context in which queen mothers foster orphans? In particular, how do queen mothers’ positions as traditional leaders, HIV and AIDS, poverty, and external assistance programs (state and NGO) all shape the organization of orphan care? (2) What are the challenges for depending on the Queen Mothers Association to support orphans? (3) How are orphans’ needs identified and described (from the perspectives of the caregiver, the orphans and those who assist them). In particular, can community-derived measures of childcare rather than the current measures typically used in international development and children’s projects provide better indices of the needs of children after losing a parent?
Towards a Poetics of Bafflement: the Politics of Elsewhere in Contemporary Black Diaspora Visual Practice (1990-Present)
Keywords: aesthetics
black diaspora
humanism
queer theory
racial slavery
visuality

Towards a Poetics of Bafflement asserts that blackness baffles—confuses and frustrates—the order of knowledge that deems black subjectivities as pathological. This dissertation argues for the importance of the psychic and affective spaces that emerge in the work of contemporary black women and queer artists. A poetics of bafflement is foregrounded by racial slavery and diaspora formations that inform contemporary racial antagonisms. The visual work of Deana Lawson, Zanele Muholi, and Mickalene Thomas, if read through a poetics of bafflement, engages blackness differently and conceptualizes new possibilities for world making. Black artists have long since occupied spaces of creative and critical thinking about aesthetics, race, and the politics of vision, which inform contemporary social, historical, and cultural climates. Multiculturalism and subsequent post-race concepts are inadequate in thinking about alternative possibilities of world making as they suggest racism and anti-black sentiment are somehow no longer prevalent. Multiculturalism’s claim of diversity negates the continued logics of anti-black sentiment, whereas post-racial suggests a time and place in history where race no longer informs political, economic, and socio-cultural experiences. Black cultural production continues to be at the crossroads of these debates. The complex interplay between race anxieties and the politics of contemporary visual culture remains opaque, even as it proliferates. Deana Lawson, Zanele Muholi, and Mickalene Thomas are among a generation of artists who have gained a certain level of North American and European recognition. Common to many of these artists is a concern with the limits of form and genre, particularly in relation to the photographic image, the queer body and the undoing of gender, and ruminations on desire and the erotic. Towards a Poetics of Bafflement responds to the absence of affect studies in addressing racial slavery—and, specifically, bafflement’s imprint on the present.
Stochastic Optimization Approaches for Performance-based Contract Evaluation
Keywords: Design of Experiments
Maintenance
Performance-based Contracting
Real Options
Reliability Engineering
Stochastic Programming

Performance-based contracting (PBC) is a relatively new type of contracting promising to deliver higher capital equipment performance and better align the interests of customers and suppliers. In PBC, unlike traditional contracting, the customer pays the supplier for the performance of the asset, not for the resources used in the maintenance services. This dissertation applies stochastic optimization approaches for PBC evaluation to investigate the contractual elements quantitatively and help the contractual parties in three distinct ways. Firstly, we use stochastic programming with simple recourse on the side of the customer. We consider scenario-based stochastic programming models for capital equipment consisting of a single component to evaluate PBC alternatives. The model measures the deviation of implied operational availability and realized operational availability within a limited budget. The readiness risk of contracts is also computed by determining conditional value-at-risk to provide insight for the customer. Secondly, we evaluate PBC from the supplier's standpoint using real options theory. We use approximation scheme to decide the best time to replace the asset. The supplier's objective is to maximize his revenue by determining the optimal asset replacement time in the face of uncertainty in asset performance. Asset performance is assumed to follow a stochastic process, and we use stochastic dynamic programming to calculate the option price. Finally, we address the problem of PBC evaluation by considering a principal-agent model for structuring PBC along with two other common types of contracts: fixed-cost and cost-plus contracts. We apply stochastic mathematical programming with equilibrium constraints to evaluate the combination of contracts. The risk of cost uncertainty is incorporated into the model to relieve the impact of extreme and unexpected events that may happen in practice. With these three models, the dissertation demonstrates how PBC evaluation can be conducted by considering uncertainty in asset performance and contract parameters; it shows how each party can achieve the best outcome.
Why Don’t We Do Something? The Societal Problematization of “Homelessness” and the Relationship between Discursive Framing and Social Change
Keywords: activism
advocacy
history of Canadian homelessness
homelessness
social constructionism
social problem studies

Despite decades of public support for ending homelessness, there is little evidence that homelessness has decreased in Canada. Instead, Canadian communities continue to respond to rising numbers of people without homes through emergency response measures that do little to prevent or end the problem. In sharp contrast, research has documented that homelessness is not inevitable and can be addressed with relatively insignificant government financing. Canada has the ability to end this problem. The question is: why don’t we? This study explores Canada’s political response to this issue by tracing the social construction of “homelessness” since its emergence in the 1980s. Drawing on social problem theory, this interpretive study uses a grounded theory approach to explore the construction of this problem by homelessness advocates and the Canadian media. Triangulating this data with social policy and key events, this study proposes a stage model to explain the “career” of this social problem. This research constitutes the first comprehensive study of the development of homelessness as a social problem in Canada. Results of the study suggest that homelessness has progressed through six stages in Canada and currently stands at a crossroads between institutionalization and transformation. Over the history of this problem, understandings of this issue have shifted from an emergency/disaster framework to an economic, bureaucratic, and scientific framework. Shifts in homelessness advocacy have been crucial to this transformation and are reflected in the development of two distinct “waves” of homelessness advocacy over the course of this problem’s history. This study argues that the differences between these waves are structurally produced through each wave’s divergent class-based experiences of early twenty-first century social and political changes. This study also offers the largest historical analysis of Canadian newspapers’ coverage of homelessness to date. Analysis revealed that newspaper coverage peaked in 1999 and has since declined. Findings suggest that Canadian reporters have frequently depoliticized and individualized this issue in class-based ways, while often failing to elucidate the connections between homelessness and Canada’s economic and social policies. This thesis concludes with an analysis of the contributions of this study to social problem studies, homelessness research, and social work.
Quantum Spin Liquids in Kitaev and Kagome Systems
Keywords: Spin Liquids
Topological Order

Quantum spin liquids, systems in which quantum fluctuations prevent the magnetic ordering of the spin degrees of freedom down to zero temperature, have been the source of much recent theoretical and experimental interest. These systems are characterised by their long ranged entangled states, preserve symmetries down to zero Kelvin, and have been shown to exhibit fascinating properties such as a topological ground state degeneracy and fractionalised spin excitations. In this thesis, we study several of these phases. The first, Kitaev spin liquids, appear in strongly spin-orbit coupled systems, where the SU(2) spin symmetry is broken. Within our mean field approach, we study the quantum phase transition from the gapless Z 2 spin liquid to a magnetically ordered phase within the Heisenberg-Kitaev model. Beyond the mean field theory, we argue that the gauge structure of the spin liquid plays a crucial role in this transition, leading to a confinement of spinons and the generation of magnetic order. We also discuss the three-dimensional iridate compounds, where the Kitaev spin liquid phase has topologically protected bulk and surface excitations. We next discuss spin liquids appearing on the geometrically frustrated kagome lattice. First, we consider non-Kramers spin liquids, in which the spin structure of the theory is protected by lattice, rather than time-reversal, symmetry. As a result, more phases are allowed, which have different properties than those which transform as Kramers doublets. In addition, these may have positive experimental signatures in the Raman scattering intensity, offering a clear path to detect such a state. Finally, we examine possible spin liquid phases on a breathing kagome lattice, where we find a stable Z2 spin liquid to be the ground state. This may help to guide future numerical studies of the kagome lattice Heisenberg model, and may also be relevant to DQVOF, a recently discovered spin liquid candidate compound.
Extracellular Matrix-mediated Lung Epithelial Cell Differentiation
Keywords: Development
Epithelial cells
Lung
Regenerative Medicine
Stem cells
Tissue Engineering

Differentiation of functional lung epithelial cells from pluripotent stem cells holds the potential for applications in regenerative medicine. However efficient differentiation to proximal and distal lung epithelial cell populations remains a challenging task. The three-dimensional extracellular matrix scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. The development of matrices that can recapitulate the in vivo environment is key for directing lung lineage-specific differentiation. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native matrix alone using decellularized adult lung scaffolds. The decellularization procedure was optimized and the scaffolds generated were carefully characterized to ensure complete removal of resident cells and preservation of the ECM. Lung scaffolds were recellularized with mouse and rat embryonic stem cell-derived endoderm and maintained for up to three weeks of culture at air liquid interface, in defined, serum-free medium conditions. Recellularization of lung scaffolds with endodermal cells resulted in differentiation to early NKX2-1+/SOX2+ proximal lung progenitor cells and a heterogeneous basal epithelial cell population, within seven days of culture. Extended culture resulted in robust differentiation to mature airway epithelia, complete with FOXJ1+/TUBB4A+ ciliated cells and SCGB1A1+ secretory club cells, with morphological and functional similarities to native airways. Differentiated day 21 cells contained beating ciliated cells in culture and exhibited functional CFTR protein expression. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans (HSPG) and its bound factors on the ECM. This work demonstrates the importance of a 3-dimensional matrix environment and the role of site-specific cues for directing differentiation of pluripotent stem cells to lung epithelial cells. This is a valuable step towards uncovering ECM-mediated signaling during lung specification and offers a platform for modeling lung development and airway-related diseases using pluripotent stem cells.
Distinguishing the Role of the c-myb Proto-Oncogene in Mouse Models of Cardiovascular Disease
Keywords: atherosclerosis
blood pressure
c-myb
differentiation
progenitor cells
restenosis

Despite considerable advances in our understanding of disease processes, cardiovascular diseases remain the top cause of mortality and morbidity in society today. Investigating the molecular and cellular mechanisms involved in the pathogenesis of these diseases to discover new therapeutic targets is of utmost importance. While much is known about the specific roles of transcription factor c-myb in leukocytes, comparatively little is known about c-myb in the context of cardiovascular disease. c-myb regulates vascular smooth muscle cell (VSMC) differentiation from embryonic stem cells, as well as the proliferation of mature VSMCs. The literature points toward several areas of opportunity to examine the role of c-myb in cardiovascular biology: first, to examine the role of c-myb in the regulation of adult vessel-resident VSMC progenitor cell proliferation and differentiation in response to vessel injury and the molecular mechanisms involved in c-myb-mediated VSMC differentiation. Second, while transgenic models manipulating c-myb have yielded significant insight in regards to homeostasis of the immune system, little is known about a role for c-myb in the regulation of baseline function of the cardiovascular system. While c-myb regulates VSMC differentiation and pathological VSMC proliferation, it is not known if it regulates VSMC contractile function and vascular contractility, and more generally, blood pressure homeostasis. Lastly, this dissertation examines the involvement of c-myb in experimental atherosclerosis, a disease model involving both leukocytes and vessel-resident cells such as VSMCs. Therefore, work of this dissertation aims to elucidate the role of c-myb in these areas and thus further the collective understanding of the mechanisms involved in cardiovascular pathophysiology.
Barometric Books: The Atmosphere in Nineteenth-century English and French Novels
Keywords: Almanacs
Atmosphere
Print culture
Sound studies

“Barometric Books: The Atmosphere in Nineteenth-Century English and French Novels” examines how popular print culture mediates representations of the atmosphere in nineteenth-century English and French novels that were published within a twenty-five year span. Charlotte Brontë’s Jane Eyre (1847) and Villette (1853), Elizabeth Gaskell’s North and South (1854), Charles Dickens’s Hard Times (1854), and Jules Verne’s Vingt Mille Lieues sous les mers (1869-70) were informed by documents, such as almanacs and serials, that define the atmosphere in terms of its ubiquitous fluidity. Explained as an overarching liquid presence, the atmosphere becomes the primary medium of existence. It is invested with the capacity to unite humans to their environment, to each other, and to sensory experiences. As the nineteenth century progresses, the atmosphere’s literary representation shifts. Its chemical composition is simultaneously altered by unprecedented industrial development, and its perception changes following developments in meteorology, a newfound science that emerges at the midpoint of the century. Over the course of these transformations, the atmosphere’s planetary presence erodes—once perceived as an invisible fluid shared by every living thing on Earth, the atmosphere is gradually transformed into a commodity, its finitude forgotten and its permeating presence thrust to the background. This project recuperates popular and ephemeral print materials. In doing so, “Barometric Books: The Atmosphere in Nineteenth-Century English and French Novels” shows how current resistance to the idea of climate change is informed by a shift that fundamentally altered how the atmosphere is represented in literature.