VictorJuiz/thesis huggingface dataset:
Nanog Regulates Chromatin Organization in Mouse Stem Cells
Keywords: chromatin
nanog
electron spectroscopic imaging
stem cell

Mouse embryonic stem cells (ESCs) are known to possess an “open” global chromatin architecture characterized by dispersed chromatin fibres throughout the nucleus. This is in contrast to differentiated cell types, where chromatin generally congregates into numerous compact domains. Core transcription factors in ESCs regulate many genes involved in maintaining pluripotency and previous research has hinted a connection between these factors and chromatin organization. My hypothesis is that Nanog, one of the core transcription factors, functions in maintaining an “open” chromatin organization in mouse ESCs. In this study, the chromatin organization in ESCs expressing varying levels of Nanog was examined at the sub-micron level through electron spectroscopic imaging. An inverse correlation was identified between Nanog expression level and the chromatin fibre density in constitutive heterochromatic regions. Furthermore, global chromatin in the more differentiated epiblast stem cells became less compact upon Nanog overexpression. Altogether, these findings support the idea that Nanog plays a role in maintaining dispersed chromatin in mouse ESCs.
Explicit Legal Protections for Transgendered Canadians: Why it is Necessary and How it Might be Done
Keywords: Law
Transgender

Explicit legal protections for trans individuals are necessary in Canadian human rights and antidiscrimination jurisprudence. The current grounds of protection against discrimination that trans individuals must rely upon (i.e., sexual orientation discrimination, disability discrimination and sex discrimination) insufficiently recognize trans individuals and the trans discrimination they face. I propose that a multi-level framework of explicit legal protections is required to address these insufficiencies. This framework includes the recognition of an analogous ground of Gender Identity and Gender Expression under the Charter, amendments to human rights legislation incorporating trans protections into prohibited grounds of discrimination at federal and provincial levels, and finally explicit recognition of trans individuals and trans discrimination in legal arguments and in litigation. This framework will allow for mutual reinforcement at multiple levels and promote development of trans specific jurisprudence. With such explicit legal protections in place trans individuals will be better protected against trans discrimination in Canada.
Lymphatic Drainage from the Mouse Eye and the Effect of Latanoprost
Keywords: lymphatics
mouse
eye
quantum dots
in vivo imaging
latanoprost

Glaucoma is a leading cause of world blindness, often associated with elevated eye pressure. Current glaucoma treatments aim to lower eye pressure by improving aqueous humor outflow from the eye. Ocular lymphatics have been demonstrated to contribute to aqueous humor outflow in human and sheep. It is not known whether any glaucoma drugs target this lymphatic drainage. The mouse is a valuable model with similar aqueous humor dynamics and pharmacology as human. Using in vivo hyperspectral fluorescence imaging combined with intracameral quantum dot injection, we identified an ocular lymphatic drainage in mouse. Immunofluorescence and confocal microscopy revealed lymphatic channels in the ciliary body, sclera, and orbit that may be responsible for this lymphatic drainage. We showed that latanoprost, a prostaglandin F2&alpha; analog widely used to treat glaucoma, increases this ocular lymphatic drainage. Our findings provide the framework for future development of novel glaucoma drugs that stimulate the ocular lymphatic drainage.
Factors Associated with Clinicians’ Recommendation for Return to Work in Patients with Work-related Shoulder and Elbow Injury
Keywords: Return to Work
Clinicians' recommendation
Work Related Injury
Sholder and Elbow
WSIB
MCS score
Mental Health
SF-36 Score

Background: RTW after work-related injuries is a multifactorial process. Factors affecting clinicians to make RTW-recommendations for patients with WRSEI have not been studied in the literature. Purpose: We investigated the associations between group of factors chosen from different domains (Personal/Environmental) and clinicians’ RTW-recommendations for patients with WRSEI. Methods: Study design was cross-sectional. Data were collected from self-reported surveys and clinical charts of 130 adult workers (not working at the time of visit and referred to WSIB-Shoulder & Elbow Specialty Clinic-Toronto) with chronic (≥6-months) injuries. Results: Population mean age was 43.5-years. 52% were female. The average time-since-injury was 20.4-months (45%>12-months). 70% received RTW-recommendations (regular/modified-job). 30% received a No-RTW-recommendation. 42% had education≥college-level. 18% had heavy (>20kg) job-demands. Higher MCS-scores had a significant association (p=0.0003) with clinicians’ RTW-recommendations. Conclusion: In patients with chronic WRSEI(s), poor general health-status and high disability, workers with better mental-health were more likely to receive a RTW-recommendation by clinicians.
Development of a Novel Imaging Methodology for Quantitative Analysis of the Mouse Cortical Vasculature
Keywords: Medical
Biophysics

This thesis describes a novel imaging methodology for visualization and quantitative analysis of the vascular topology of different cortical regions of the mouse brain in 3D. The brain is perfused with a fluorescent contrast agent, and rendered fully transparent via optical clearing. This procedure enables images through the whole cortical depth to be obtained with a 2-photon microscope without sectioning. The Allen Reference Atlas (ARA) (Lein et al., 2007) is registered to the 2-photon data for delineation of the cortical regions. Quantitative metrics are then extracted from the different regions using an automatic vessel segmentation algorithm. These metrics are compared with those obtained by other investigators to validate this technique, and are found to be in agreement. Since this methodology possesses the resolution to visualize vessels of all sizes, and provides reasonable estimates of quantitative parameters, it shows strong potential for quantitative analysis of normal and abnormal cortical vascular architecture.
Intermittent Water Supplies: Where and Why they are Currently used and Why their Future use Should be Curtailed
Keywords: Intermittent Water Supply

Though water is the most essential element of life in most developing countries clean drinking water is supplied intermittently to consumers. Municipalities are often under the impression that intermittent supply is an ideal measure to conserve water. With over a billion people grappling with deteriorating infrastructure and water scarcity, it is impossible to neglect the effects of intermittent supply. It is essential to examine the origin of the problem, quantify the effects or consequences and then provide feasible solutions. Hence, this thesis provides a comprehensive review of the existing condition of water supply systems in developing countries but more importantly, examines the causes of the intermittency and highlights the significant economic incentive that could be achieved by maintaining a continuous supply system. Finally the thesis concludes with a series of feasible solutions including short-term and long-term plans that would assist in a complete migration towards 24-hour supply.
Crosstalk between VEGF and BMP9 Signalling in the Context of Preeclampsia
Keywords: Preelcmapsia
soluble endoglin
endothelin-1
VEGF

Preeclampsia is a pregnancy related disorder, characterized by proteinuria and hypertension. The pathogenesis of preeclampsia is poorly understood; however, two proteins, called sFlt-1 and sEng, were found to be highly elevated in the maternal plasma weeks prior to the onset of clinical symptoms. sFlt-1 and sEng are thought to inhibit VEGF and TGF-β receptor signalling respectively. In order to elucidate how these proteins may contribute to preeclampsia, we looked at their ability to affect the secretion of endothelin-1 (ET-1), a powerful vasoconstrictor, shown to be dysregulated in preeclampsia. We found that both TGF-β1 and BMP9, a recently described ligand for sEng, induce ET-1 secretion through Smad1/5/8 and p38 pathways. Moreover, we report that sEng and VEGF can efficiently block ET-1 secretion, induced by BMP9. We propose that the balance between VEGF and BMP9 signalling is disturbed during preeclampsia, leading to excessive release of ET-1, which in turn may cause hypertension.
Evaluation of the Accuracy of NaviDent, a Novel Dynamic Computer-guided Navigation System for Placing Dental Implants
Keywords: implant dentistry
implant surgery
guided surgery
computer-aided
computer-guided
navigation
surgical guide

Objectives: To evaluate and compare an experimental surgical navigation system (ESNS) in implant placement accuracy to static planning and transfer systems. Material and Methods: Partially edentulous, surgical typodonts were used to simulate prosthetically-driven osteotomies in preclinical setting. After cbCT acquisition the DICOM files were used to reverse plan and fabricate surgical guides. Manual placement, three static guiding systems and ESNS were compared. Eight osteotomies per jaw were transferred to 10 typodonts in five series, resulting in 400 osteotomies by 3 operators, each modality. Lateral, vertical, total and angular deviations were measured and compared. Results: Computer-assisted systems were comparable and provided superior precision laterally and in angulation, but not vertically; implants placed in free-end positions were less accurate. Conclusions: All computer-aided methods showed less than 2 mm or 5 degrees error on average, which needs to be considered in clinical practice.
Hostile Takeovers and Corporate Purpose: The Role of Poison Pills in Ontario Securities Law
Keywords: corporate law
hostile takeovers
poison pills

This paper examines the Ontario Securities Commission's regulation of poison pills as well as several proposals to reform the current regulatory regime. In particular, the paper argues that regulation and reforms should be viewed within the context of two fundamental, normative questions that underlie much of corporate law: what is the purpose of the corporation, and who should determine whether these goals are being met. After outlining several competing theories, the paper explains why a corporate model based on the shareholder-centric, wealth maximization theory is best suited for hostile takeover situations. Additionally, the paper argues that a structural bid reform that would require hostile bidders to include minimum tender conditions and additional opportunities for target company shareholders to tender following a successful bid would provide the best way to incorporate this corporate model into Ontario securities regulation.
Legal Absurdities and Wartime Atrocities: Lawfare, Exception, and the Nisour Square Massacre
Keywords: Iraq war, Nisour Square, Lawfare, Legal Geography, State of Exception, PMSC, PMC, private security contractors

According to the United States Department of Defense (DOD), as of 2013 there were over 12,000 DOD contractors supporting the U.S. mission in Iraq (DASD, 2013). This thesis explores the laws and legal systems that operate to keep contractors, and the companies that employ them, resistant to legal oversight. I ground my analysis in the 2007 Nisour Square massacre, exploring how every attempt to prosecute those responsible was doomed due to Blackwater’s legal position of being American-headquartered, hired by the State Department, privately owned, and operating in Iraq. I conclude that the legal indeterminacy of the US deployed security contractor normalizes violence towards Iraqi civilians while simultaneously downloading the risk and responsibility associated with the US war efforts onto the shoulders of individual contractors. Moreover, I suggest that this legal indeterminacy is of particular interest to geographers as it arises, in part, out of overlapping legal systems, jurisdictions, and authorities.
A Cluster Randomized Controlled Trial of Prenatal Education to Improve the Use of Pain Management Strategies during Infant Immunization
Keywords: pain management
infant
analgesic
immunization

Background: Unmitigated immunization pain in infants has the potential to impact long-term health outcomes. Teaching parents in the prenatal period may increase utilization of pain management (PM) strategies in clinical practice. Objective: To assess the efficaciousness of teaching parents in the prenatal environment and its impact on the number of analgesic PM strategies utilized during the 2-month immunization appointment. Methods: This partially blinded cluster randomized controlled trial enrolled mothers from prenatal classes at Mount Sinai Hospital. Classes were randomized to receive a presentation on either immunization PM or general immunization information. Results: One hundred and ninety-seven mothers from 28 classes participated in this study. There was a statistically significant increase (p<0.01) in the use of one or more analgesic interventions in the group that received a presentation on immunization PM compared to those who received general immunization information. Conclusions: Prenatal classes are a suitable environment to educate parents about immunization PM.
Effects of Dopamine Antagonists on Gambling Reinforcement and the Impact of Prior Exposure in Pathological Gamblers and Controls
Keywords: dopamine
d1 receptor
d2 receptor
pathological gambling
haloperidol
fluphenazine
novelty

This study sought to determine the roles of D1 and D2 receptors in mediating gambling reinforcement in pathological gamblers and controls (n=24/group), and the influence of reward novelty on these effects. Subjects received D2 antagonist, haloperidol (3mg), or D1-D2 antagonist, fluphenazine (3mg) in a placebo-controlled, counterbalanced, two-session design. Incentive motivation and hedonic impact were assessed before and after a 15-min slot machine game. Haloperidol tended to increase pre-game motivation but reduce the priming effect of the slot machine, while fluphenazine increased positive mood ratings but reduced motivation to gamble. Haloperidol effects were stronger when it was received on the first session, while fluphenazine had stronger effects after prior drug-free exposure. Results suggest D1 signaling is central to reward expectancy and motivation to gamble, and that moderate stimulation increases positive affect while reducing motivation to gamble. D1 blockade may also enhance reinforcement of a familiar task by interfering with reward expectancy.
Unsettling the Currency of Caring: Promoting Health and Wellness at the Frontlines of Welfare State Withdrawal in Toronto
Keywords: community organizers
Welfare State Withdrawal
Neoliberal restructuring
Funding and Philanthropy
stress and burnout
non-profit industrial complex
health and wellness

What does the prevalence of stress and burnout in community-based work reveal about the impacts of welfare state withdrawal? Drawing on the experiences of frontline community organizers in Toronto, this research argues that welfare state withdrawal is subsidized by a ‘Currency of Caring’ whereby frontline community organizers are expected to fill gaps in the social safety net, working to a point of burnout if necessary, because they care. This research investigates how funders operating within this context can promote health and wellness in community-based work. Broadly, research findings provide insights into how neoliberalism and welfare state withdrawal shape frontline community work in ways that exacerbate stress and burnout, and impede systemic change efforts. In addition, research findings describe the limitations and possibilities for funders to be allies in collective change efforts by being invested in the health and wellness of frontline community organizers.
Design and Development of a Contactless Planar Capacitive Sensor
Keywords: capacitive sensor
respiration monitoring

The measurement of vital signs is a risk-free, inexpensive, and reproducible clinical practice that enables identification of physiological deterioration of patients before an adverse event occurs. However, studies show that manual clinical measurements of respiratory rate are intermittent, biased, and inaccurate. Therefore, a contactless planar capacitive sensor was developed and evaluated against a clinical reference method. Results show that the sensor is accurate (i.e. strong agreement with an average ICC value of 0.99 and an average BSI coefficient of 2.76 < 4 breaths/min clinical threshold) and unbiased (i.e. average mean difference of -0.02 breaths/min). The sensor has promise for respiratory rate monitoring of bedridden patients even during shallow breathing. Future work includes addressing technology limitations, conducting a clinical pilot with a diverse patient population, and exploring potential in sleep quality assessment.
Lipid Accumulation in CD11c-expressing Intimal Myeloid Cells Induces Chemokine Production Required for Leukocyte Recruitment to Early Atherosclerotic Lesions
Keywords: Atheroscleorsis
Leukocyte Recruitment
Intimal Myeloid Cells
CD11c
Lipid Accumulation
Chemokines

Monocyte recruitment promotes the accumulation of myeloid foam cells in early atherosclerotic plaques. However, initial foam cells form prior to increased monocyte recruitment in hypercholesterolemic Ldlr-/- mice. These initial foam cells are derived from myeloid cells residing in the normal intima, and express integrin alphaX (CD11c). The goal of this thesis was to assess the role of initial foam cells in atherogenesis. The approach was to delete these cells by diphtheria toxin-induced apoptosis in Ldlr-/- bone marrow chimeras. Depletion of CD11c+ leukocytes resulted in significant reductions of intimal lipid accumulation, monocyte recruitment, intimal chemokine expression, but not endothelial cell adhesion molecule expression, at 10 and 21 days of hypercholesterolemia. These data suggest that lipid uptake by resident intimal CD11c-expressing myeloid cells during the earliest stages of atherosclerosis promotes chemokine production that is required for increased monocyte recruitment.
Controlled Conjugation of [Cu,Zn] Superoxide Dismutase: An Active Tetramer
Keywords: Superoxide Dismutase
Bioconjugation

While the catalytically powerful [Cu,Zn] superoxide dismutase (SOD1) possesses great potential as a therapeutic, unfavorable properties in circulation limit its use in clinical medicine. The small, water soluble dimer is rapidly excreted by the kidney. Previous initiatives have been used to increase the mass of the enzyme (PEGylation, liposome encapsulation). This has resulted in highly heterogeneous mixtures of modified SOD1, which are difficult to characterize. Furthermore, these modified proteins have utilized foreign material that has shown to elicit an inflammatory response. We developed an improved strategy that creates a homogenous high molecular weight SOD1 based on combinations of the protein itself. This was accomplished through the addition of a site-specific, azide functionalized cross-linker to unmodified SOD1, followed by the conjugation of SOD dimers using CuAAC and a bis-alkyne linker to form a 64 kDa SOD tetramer. The final product, bis-SOD, presents the fully catalytic activity of the combined proteins.
Spiritual Journal Keeping: An Ethnographic Study of Content, Materials, Practice, and Structure
Keywords: ethnography
information studies
information behaviour
journal keeping
spirituality
catholicism

This thesis reports the findings of an exploratory, ethnographic study of the spiritual journal keeping practices of Catholic university students at the 'Harbour House,' a Catholic student centre and parish operating on the campus of a large, Canadian university. Guided by the question,'How and why do Catholic students keep journals to document their spiritual lives?' it examines journal keeping in the context of Catholic spirituality, the relationships students have with their journals as spiritual documents, and the representations of information found in spiritual journals. Findings are organized under the themes of Content, Materials, Practice, and Structure, and demonstrate that spiritual journal keeping is a deeply personal activity that involves a variety of unique and individualized information practices and behaviours, developed and used in order to better navigate a vast and mysterious spiritual path, and to work towards spiritual growth.
Robust Facility Location under Demand Location Uncertainty
Keywords: optimization
facility location
healthcare operations

In this thesis, we generalize a set of facility location models within a two-stage robust optimization framework by assuming each demand is only known to lie within a continuous and bounded uncertainty region. Our approach involves discretizing each uncertainty region into a set of finite scenarios, each of which represents a potential location where the demand may be realized. We show that the gap between the optimal values of the theorized continuous uncertainty problem and our discretized model can be bounded by a function of the granularity of the discretization. We then propose a solution technique based on row-and-column generation, and compare its performance with existing solution methods. Lastly, we apply our robust location models to the problem of ambulance positioning using cardiac arrest location data from the City of Toronto, and show that hedging against demand location uncertainty may help decrease EMS response times to cardiac arrest emergencies.
Induction of Tolerance: Mechanisms and Implications for Clinical Transplantation
Keywords: Transplantation
Tolerance

Therapies that promote tolerance will improve outcomes in solid organ transplantation by eliminating the need for long-term immunosuppression. This thesis investigates two possible tolerance induction mechanisms: rapamycin induced expression of regulatory T cells and re-education of the immune system using syngeneic hematopoietic stem cell transplantation. Fibrinogen-like protein 2, a effector molecule of regulatory T cells, was also determined as a key mediator in the tolerance induction pathway as depletion of fibrinogen-like protein 2 lead to allograft rejection. The feasibility of using syngeneic hematopoietic stem cells for inducing allograft tolerance was studied by setting up a murine heart and bone marrow transplant model. Syngeneic T-depleted bone marrow transplantation resulted in a slight prolongation of the graft survival time compared to the animals reconstituted with total bone marrow cells. We provide compelling evidence to suggest that fibrinogen-like protein 2 and syngeneic hematopoietic stem cells can possibly be used to induce transplantation tolerance.
Arrays of Silicon P-i-N Nanowires for Antenna-enhanced and Polarisation Sensitive Detection of Light
Keywords: Nanowires
Silicon
Optical sensor

A novel antenna effect is demonstrated in arrays of 500, 200 and 100 silicon nanowires embedded in silicon dioxide. The gratings are analyzed using spectral and polarisation resolved photocurrent microscopy. Resonant enhancements in the electric field and photocurrent response are observed at multiple wavelengths corresponding to coupling of incident radiation into the grating's multiple-scattering electromagnetic modes. The photoresponse retains the sinusoidal polarisation anisotropy expected in single nanowires. The resonances are modeled using electromagnetic scattering theory and show excellent agreement with measurement. An experimental quality factor of Q=10 was measured for the gratings, exceeding that of a single wire, but lower than expected from theory. The difference is ascribed to the finite length of the wires and their termination at ohmic contacts. Strategies to improve Q are discussed, and a grating is presented to resonantly enhance light detection at red, green and blue wavelengths for application as a colour imaging sensor.