VictorJuiz/thesis huggingface dataset:
Innate Immune Response Polarization and Treatment Potential in a Pre-clinical Model of Dry Age-related Macular Degeneration
Keywords: Age-related macular degeneration
Fundus autofluorescence
Geographic atrophy
Macrophage polarization
Retinal pigment epithelium

Age-related Macular Degeneration (AMD) is the leading cause of blindness in the Western world, depriving older individuals of their central vision and their autonomy. At present, no treatments exist for dry AMD, nor are there animal models that reproduce the complex clinical fundus autofluorescence (FAF) findings of end-stage blinding complications, such as geographic atrophy (GA) - patches of tissue loss of the RPE and overlying neuroretina. The objective of this study was to characterize the immune response and macrophage polarization in a rodent model of GA using clinically relevant imaging modalities, and determine whether modulation of this response would alter atrophy progression. We administered sodium iodate to Sprague Dawley rats to induce loss of the RPE and subsequently the photoreceptors, resulting in retinal atrophy, and monitored the changes using a clinical confocal scanning laser ophthalmoscope (cSLO). Using the FAF channel typically employed for patients in the clinic, we have characterized five stages of atrophy progression that occurs over the period of acute RPE loss and chronic tissue response. This was further observed with our newly developed Delayed Near-Infrared Analysis (DNIRA) technique in the near-infrared channel. This novel finding also led us to detect macrophages in the areas of bright FAF, and using modified DNIRA techniques we have been able to identify and track macrophages directly in vivo. By using inflammatory markers and quantitative PCR for polarized macrophage phenotypes on retinal and eyecup tissue samples, we identified that inflammatory M1 macrophages can be detected during the stages of atrophy progression, and that the overall tissue profile is heavily skewed towards M1 polarization. By employing intraocular gadolinium chloride and subsequently an M1-blocking drug bindarit to prevent the macrophage response, we have shown that atrophy can be prevented and that the in vivo and tissue phenotypes can be virtually normalized if inflammation is blocked. On the other hand, by further propagating the inflammatory response by combining NaIO3 with nitroglycerin, the atrophy is expanded, which can also be subsequently blocked by bindarit. These unprecedented findings have strong implications for translation to the clinical setting for the diagnosis, monitoring and treatment of late stage dry AMD.
Glutamatergic mechanisms in behavioural sensitization to ethanol
Keywords: Addiction
Ethanol
Glutamate
Locomotor activity
NMDA receptor
Sensitization

Repeated exposure to ethanol (EtOH) in mice produces behavioural sensitization. However, not all mice sensitize to EtOH and in any cohort high-sensitizers (HS) can readily be distinguished from low-sensitizers (LS). The neural mechanisms mediating vulnerability and resistance to EtOH sensitization remain unclear. Given the prominent role of glutamate in neuroplasticity, we examined whether this system might explain the variable response to EtOH. In the first set of experiments, we measured nucleus accumbens (NAc) glutamate levels in LS and HS mice following an EtOH challenge two weeks after sensitization development. EtOH-induced glutamate release in the NAc was present in HS mice and use of a glutamate release blocker prevented the expression of sensitization. To ascertain whether NAc glutamate was also elevated in HS mice during the development of sensitization, we measured levels after the 1st and 5th EtOH injection and found them unchanged in HS mice. These results suggest that NAc glutamate may not be necessary for the development of EtOH sensitization, but it appears essential for the expression of a sensitized response. iii We next studied the role of NMDARs in EtOH sensitization. LS mice demonstrated elevated NMDAR subunit gene expression across the brain compared to HS and saline-treated mice. However, NMDAR antagonism with MK-801 and CGS 19755 did not interfere with EtOH sensitization, indicating perhaps that NMDARs may not be crucial to sensitization. A final goal was to examine whether LS and HS mice differ in the expression of the plasticity markers pCREB, Bdnf, trkB, and Arc, and if they show structural changes in NAc neurons. HS mice showed increased pCREB expression in the NAc. LS mice showed reduced trkB and Bdnf expression across the brain, however inhibition of BDNF-TrkB signaling had no effect on EtOH sensitization. LS mice also presented greater stubby spine density in the NAc and increased Arc mRNA in several brain areas when compared to saline controls and HS mice. Taken together, these results demonstrate variation in the glutamate system between LS and HS mice. This thesis discusses these differences and how they may contribute to individual differences in sensitization response.
Investigation of Thermal, Mechanical, and Tribological Behaviour of Biobased-resin-crosslinked, Sisal-fibre-reinforced Epoxy Composites
Keywords: Bio cross-linking agent
Dry sliding wear
Epoxy composite
Phenalkamine
Polymer Tribology

The wide-reaching potential demands for exchanging petroleum-derived raw materials with renewable plant-based ones in the production of valuable polymeric materials and composites are quite substantial from the collective and ecological viewpoints. Hence, cheap renewable sources has profoundly drawn attention by many investigators for polymer composite processing. Among them, biobased resin and natural fibres are likely to be the ideal alternative feedstock, derived from plant sources, are found in abundance in the world.The significant feature of these types of materials is that they can be designed and tailored to meet diverse requirements.The actual challenge exists in finding applications, which would use adequately large amounts of these materials allowing biodegradable polymers to compete economically in the market.Absence of materialsâ s mechanical and tribological characterization have created an awareness to accomplish this crucial objective. In order to comprehend the feasibility of biobased materials incorporation in polymer composite processing for structural and tribological application , this thesis work elucidates the study of friction and wear characteristics of epoxy matrix and composites made out of biobased crosslinking agent and natural fibre available profusely in plants. An epoxy resin was cross-linked with synthetic and bio-based cross-linking agents, and the effects of this cross-linking on the resinâ s mechanical and tribological properties were investigated.The determined concentration of biobased crosslinking agent was optimized by comparing epoxy network tensile strength properties. The effect of crosslinker concentration, reinforcement agent was studied under dry sliding.The dry-sliding wear resistance property of bio-based cross-linker-cured, sisal fibre reinforced epoxy network was found to be superior, due to enhanced flexibility. The functional groups, nature of curing and degradation of epoxy resin with different crosslinking agent was studied through Fourier transform infrared spectroscopy and thermograviemetric analysis technique. The wear tracks were quantified with scanning electron microscope and optical microscope.The numerical analysis of the dry sliding wear testing process further confirmed the experimental findings as they related to the effects of normal load on the specific wear rate of composites. An empirical relationship between wear behavior and mechanical properties of epoxy network was established.
Automated Brain Mapping to Evaluate the Relationship between Neurodegeneration, Cerebral Small Vessel Disease and Structural Covariance Network Disruption in Alzheimer's Disease
Keywords: Alzheimer's disease
Brain Networks
Covariance-based connectomics
Magnetic Resonance Imaging
Small Vessel Disease
Structural covariance

Humans are currently living longer than any other period in history. However, gains in life expectancy do not portend a commensurate increase in quality of life years, particularly in persons with dementia. This is pertinent as the number of persons suffering from Alzheimerâ s disease (AD) is expected to double to over a million within a generation in Canada. The pathological underpinnings of AD remain unclear but are thought to target large-scale brain systems. It is posited that disease of the brainâ s small blood vessels may contribute to AD progression by disrupting structural brain networks that subserve complex cognitive routines. Therefore, the overarching aim of this dissertation is to determine the contribution of cerebral small vessel disease (SVD) versus coexistent neurodegeneration to brain network disruption in AD. The first part of this thesis presents and validates a state-of-the-art automated hippocampal segmentation technique for magnetic resonance imaging to accurately measure neurodegenerative status in mixed disease samples. The second part of this thesis assesses the relationship between hippocampal volume, SVD burden and grey matter cortico- and subneocortico-cortical network hub disruption. Finally, we extend these findings by introducing a method we call covariance-based connectomics to characterize how cortex-wide polysynaptic (grey-white matter) systems are disrupted in relation to SVD and neurodegenerative markers in AD versus age-matched controls. In summary, this thesis presents innovative human brain mapping techniques and the application of these methods to explore the relationship between SVD and AD in vivo. The SVD-signature of network disruption in AD is elucidated, and evidence is presented which supports the idea that SVD is differentially associated with neural network degradation in older adults and persons with mild AD.
Pre-operative Functional Magnetic Resonance Imaging: Application to Tumour Resection by Awake Craniotomy
Keywords: awake craniotomy
direct cortical stimulation
functional magnetic resonance imaging
glioma
language mapping
reliability

The management of brain tumours in eloquent areas remains challenging. Surgical intervention is currently the primary method of treatment, with the surgeon attempting to maximize tumour resection while simultaneously sparing healthy cortex. Pre-operative and intra-operative brain mapping techniques are capable of localizing eloquent cortex, and are thus employed to facilitate the surgical decisions. Although direct cortical stimulation (DCS) remains the gold standard intra-operative brain mapping technique, non-invasive imaging tools like functional magnetic resonance imaging (fMRI) have become increasingly popular at the pre-operative planning stage. In this thesis, technical work has been done to improve, characterize, and provide perspective on appropriate usage of pre-operative fMRI in brain tumour surgery. The thesis encompasses three specific research studies. The first, entitled “A novel tablet computer platform for advanced language mapping during awake craniotomy procedures”, describes the development of a platform that enables behavioural testing to be standardized with respect to pre-operative fMRI, and enables sophisticated testing paradigms to be administered during DCS. The testing platform is demonstrated to provide improved language mapping capabilities over current practice. The second project, entitled “Reliability of task-based fMRI for pre-operative planning: a test-retest study in brain tumour patients and healthy controls”, shows the impact of disease and technical factors on the reproducibility of fMRI activation maps. Reliability of fMRI data is shown to be comparable in low-grade glioma (LGG) patients and healthy controls, but poorer in high-grade glioma (HGG) patients. More reliable activation patterns are demonstrated for motor tasks than for language tasks. The third project explores “Sources of variation influencing concordance between functional MRI and direct cortical stimulation in neurosurgery”. This work shows the substantial extent of false positive (FP) activations that are present in fMRI results compared to DCS, the inverse relationship between fMRI sensitivity and specificity with changing statistical threshold, and that concordance is improved when behavioural tasks are standardized across fMRI and DCS. Collectively, this thesis supports that pre-operative fMRI is a suitable adjunct to DCS for surgical decision-making. The experimental findings demonstrate that the reproducibility of fMRI data and its concordance with DCS are generally good, though directly related to the quality of fMRI activation maps. Actions can be taken to optimize fMRI data quality with good understanding of the clinical and technical factors that are influential, such that neurosurgeons can interpret activation maps more reliably.
Heidegger's Nietzsche: European Modernity and the Philosophy of the Future
Keywords: Heidegger
Hermeneutics
History of Political Thought
Nietzsche
Ontology
Political Philosophy

The dissertation offers a study of two key figures in the history of political philosophy. By way of a textual interpretation of Martin Heidegger’s reading of Friedrich Nietzsche, it attempts to draw renewed attention to the question of ontology in the history of political thought. The discussion unfolds in the context of an epochal change and transition in European culture that in Heidegger’s interpretation of Nietzsche is in the process of teleological “fulfillment.” The text examines the sources of this potentially transformative event, with special emphasis on the contrast between the modern predominance of Cartesian inter-subjectivity and a manner of thought that dwells in the philosophical anthropology of classical Greek culture. The dissertation partakes in the Platonic-Aristotelian tradition of studying political science from architectonic perspectives, thereby highlighting the key comparative importance of philosophical “vision.” In that spirit, the thesis proposes to study an encounter between Heidegger and Nietzsche at the interstice between hermeneutics and contemporary political theory.
Understanding and Practice of Teaching Reading in Content Areas in Upper Elementary Classes in Suburban Public Schools in Cambodia
Keywords: Comparative and international studies in teacher education
Student centered and teacher centered approaches
Teachers' perspectives on teaching reading
Teaching practices in Cambodia
Teaching reading in content areas
Teaching reading in upper elementary classes

In Cambodia, little research has been done on how teachers teach reading in their content-area classes. Teachers’ perspectives of and knowledge and skills in teaching reading are essential links as to how well they instruct their students and how well their students learn. This qualitative case study explores teachers’ instructional strategies in teaching reading in content areas in Cambodia, using a series of teacher interviews combined with lesson observations. Although teacher-training experiences impact teachers’ understandings of reading and their selection of instructional strategies, the findings of this study suggest that Cambodian teachers have neither become familiar with reading strategies nor learned specific methods for teaching reading in content areas. Even though student-centered approaches are utilized to teach reading in content areas, these teachers did not implement them consistently and effectively, preferring traditional teacher-centered approaches and rote memorization. Other factors that influence teachers’ attitudes, beliefs, and choice of instructional strategies are also explored. More importantly, key perspectives that explain the teachers’ perspectives on teaching reading, issues and challenges they encounter, and curricular roles they adopt or could develop are identified in each analysis in the findings chapter. Thus, this study has implications regarding the improvement of: teacher education programs, reading curricula, teaching reading in content areas, and pre/in-service teacher development.
Polish Catholic Priests in Canada and Ireland: Migration, Leadership, and the Mobility of Strangers
Keywords: Georg Simmel
Lived Religion
Migration Theory
Polish Priests
Religious Leaders
Transnationalism

Scholars investigating the relationship between migration and religion have tended to focus on the role of churches and the experiences of lay immigrants when conceptualizing assimilation and transnationalism. While the role of religious leaders has received some attention, scholars have rarely considered clerics a migrant population worth examining. In this study I draw on 30 in-depth interviews with Polish Catholic priests in Canada and Ireland, ethnographic research, and content analysis of Catholic Church documents in order to investigate the experiences and narratives of clerics in terms of their own personal migrations and the role they took on in their own ethnic communities and beyond. I find that leaving Poland enabled the priests to reflect on their on Polish identity, embrace pluralism, and embody the universalism of the Catholic Church that emphasizes shared faith rather than socially constructed categories of race, ethnicity, culture, gender, etcetera. I conceptualize the migrant priest as a Simmelian stranger who interacts with a diverse group of migrants, while at the same time undergoing similar processes of assimilation and transnationalism. A Simmelian lens is useful, I argue, because it draws our attention to the simultaneity of these processes, encourages us to consider the individual experiences of priests rather than focusing solely on church structures or immigrant communities, and gives us the language to talk about different ‘strangers’ at different stages of their migration. Moreover, this project underscores the importance of context and local migration histories. Specifically, while the highly integrated Polish community in Canada meant that priests there had to shed their cultural/ethnic identity so as to fit into other communities, the priests in Ireland, where the Polish community was less settled and perhaps not there for the long term, had to balance maintaining their Polish identity with a readiness to work in other communities. It is my hope that this research illustrates the utility and malleability of classical theory for migration and religion scholars and that the focus on the narratives of priests stimulates more discussion on the experiences of individuals and their “lived religion” which occurs outside of structures in everyday life.
NCS-1 Dependent Learning Bonus and Behavior Outputs of Self-directed Exploration
Keywords: Exploration
Hippocampus
Learning and memory
NCS-1
Novel environments
Ultrasonic vocalizations

Animals explore a new environment and learn about their surroundings. â Explorationâ refers to all activities that increase the information obtained from an animal. For this study, I determined a molecule that mediates self-directed exploration, with a particular focus on rearing behavior and vocalization. Rearing can be either self-directed exploration or escape-oriented exploration. Self-directed exploration can be driven by the desire to gather information about environments while escape-oriented exploration can be driven by fear or anxiety. To differentiate between these two concepts, I compared rearing and other behaviors in three different conditions 1) novel dim (safe environment), which induces exploration based rearing; 2) novel bright (fearful environment), which elicits fear driven rearing; and 3) familiar environment as a control. First, I characterized the effects on two distinct types of environment in exploratory behavior and its effect on learning. From this, I determined that self-directed exploration enhances spatial learning while escape-oriented exploration does not produce a learning bonus. Second, I found that NCS-1 is involved in exploration, as well as learning and memory, by testing mice with reduced levels of Ncs1 by point mutation and also siRNA injection. Finally, I illustrated other behavior outputs and neural substrate activities, which co-occurred during either self-directed or escape-oriented exploration. I found that high-frequency ultrasonic vocalizations occurred during self-directed exploration while low-frequency calls were emitted during escape-oriented exploration. Also, with immediate early gene imaging techniques, I found hippocampus and nucleus accumbens activation in self-directed exploration. This study is the first comprehensive molecular analysis of learning bonus in self-directed exploration. These results may be beneficial for studying underlying mechanisms of neuropsychiatric disease, and also reveal therapeutic targets for them.
Corporate Board Health and Safety Governance Committees: Do They Make Any Difference?
Keywords: Board
Canada
Corporations
Governance
Health
Safety

A three phase mixed methods study (records research, survey, case analysis) was undertaken to develop understanding of board of director health and safety governance committees (â BHSCsâ ) amongst large market capitalization Canadian public companies, and ascertain their impact on company health and safety performance outcomes. This goal was deconstructed into a series of 12 research questions. The study determined that as of 2010, 58 companies with market capitalizations of $1.5 billion or higher (out of 146) had BHSCs. Forty percent had BHSCs dating back to 2001, and 60% formed BHSCs between 2002 and 2010. Factors accounting for the emergence of BHSCs included legislative changes, liability concerns, risk reduction objectives, corporate social responsibility pressures, emulation of peers, and industry sector guidelines and standards. Approximately 2/3rds of the companies with BHSCs were in mining or oil and gas. Most companies with BHSCs published descriptive information on their structures and processes in annual sustainability reports, and / or in filings with securities regulators. Using those sources it was possible to characterize patterns over the 2001-2010 period in the evolution of BHSC mandates, terms of reference, member composition and characteristics, levels of activity, and governance practices. Information was also available for many companies on occupational health and safety program evolution and injury rates for all or portions of the period 2002-2014. A conceptual framework consistent with available empirical research and theory was created to describe mechanisms whereby BHSCs could be instrumental in the achievement of improvements in company injury rates. Evidence for the existence and operation of those mechanisms was obtained via review of company data, survey responses, and case analyses of three specific companies. The study found evidence of BHSC instrumentality in company health and safety performance improvements, and that the conceptual framework presents a plausible model of this phenomenon.