VictorJuiz/thesis huggingface dataset:
Identifying Associations between Vascular Risk Factors and Measures of Brain Health using Multimodal Magnetic Resonance Imaging

Recent epidemiological evidence indicates that vascular risk factors (VRFs) play a significant role in cognitive decline that can contribute to the onset of dementia among older adults. The link between VRFs and dementia is supported by common neurological findings of structural deficits, cerebrovascular dysfunction and amyloid accumulation in both conditions. Despite the growing literature on VRFs and the brain, there are still many unanswered questions about their roles in pathoetiology and best imaging methods for detecting neurological effects of VRFs. The main goal of this thesis was to characterize the effect of increasing number of VRFs on brain health. Measures of structural brain integrity and cerebrovascular health were acquired using non-invasive magnetic resonance imaging (MRI). The first study of this thesis identified regions of impaired vascular reactivity and thinning of the cortical mantle in older adults with type 2 diabetes and hypertension compared to hypertension only. The next two studies focused on the associations between VRFs and brain health in two common neurodegenerative conditions: older adults with small vessel disease and older adults with mild cognitive impairment. In adults with white matter hyperintensities, a hallmark of small vessel disease, higher VRF number was associated with lower vascular reactivity in cognitively relevant regions. In older adults with mild cognitive impairment, increasing VRF number was correlated with cortical thinning in regions implicated in Alzheimer's Disease. Together, findings of this thesis highlight an association between increasing VRF number and exacerbated brain health in otherwise healthy older adults and individuals with comorbid neurodegenerative disorders. To conclude, the implications of these findings for clinical practices are discussed with focus on proper VRF management as well as the need to properly account for VRFs in neuroimaging studies.

Keywords: cerebrovascular disease
Magnetic resonance imaging
structural imaging
vascular reactivity
vascular risk factors
Advisor: MacIntosh, Bradley J
Evaluation of BDNF, Calcium Homeostasis and Cell Growth in Two Putative Disease Reporter Models of Bipolar Disorder

The pathophysiology of bipolar disorder (BD) involves aberrant functioning at the molecular and cellular levels, including alterations in the BD biomarkers brain-derived neurotrophic factor (BDNF) and intracellular calcium homeostasis (ICH). However, disease- and cell-type relevant models for the examination of the disturbances in BD have been limited. To this end, I sought to explore the validity and utility of the B Cell Lymphoblast Cell Line (BLCL) and Olfactory Neural Precursor (ONP) cell models in the study of BD pathophysiology, focusing on the pathophysiological significance of BDNF and ICH. BDNF protein expression was examined in BLCLs derived from lithium-responsive BD subjects, their unaffected relatives, and healthy controls (HC). In the neurally-relevant ONP cell lines, cell viability, cell proliferation, BDNF expression and basal intracellular calcium ([Cai2+]B) levels, as a marker of ICH, were determined. This thesis work demonstrated lower BDNF levels in BLCLs derived from BD subjects compared to both their unaffected relatives and HC. BDNF levels in both treatment groups were also significantly decreased after cellular lithium treatment. After confirming that ONPs could be differentiated along a neural lineage, I then demonstrated that cell number is increased in ONPs in response to lithium treatment, and that ONPs derived from BD subjects have increased cell survival. Finally, in both treatment groups, BDNF protein and mRNA levels from ONPs decreased from 24 hour to 7 days, while lithium treatment resulted in a modest but significantly increased [Cai2+]B. These results suggest an important role that lithium, due to its impact on cell proliferation, may have on neurogenesis. More importantly, increased ONP cell survival in BD supports a pathophysiological mechanism in BD, possibly affecting neurogenesis. Furthermore, the ONP model emerges as a disease- and cell type-relevant platform to examine the mechanistic and genetic basis underlying these abnormalities. These findings support the use of ONPs as a promising model for neuropsychiatric drug discovery.

Keywords: BDNF
Bipolar Disorder
Calcium Homeostasis
Cell Growth
Olfactory Precursor
Stem Cells
Advisor: Warsh, Jerry J
Exploring Many Body Interactions with Raman Spectroscopy

Many-body interactions are cornerstones of contemporary solid state physics research. Especially, phonon related interactions such as phonon-phonon coupling, spin-phonon coupling and electron-phonon coupling constantly present new challenges. To study phonon related many-body interactions, temperature dependent Raman spectroscopy is employed. Firstly, a new design and construction of a Raman microscope aimed at high collection eciency, positional and thermal stability is discussed. The application of the home-built Raman microscope is shown in the context of two types of novel materials; Cr2Ge2Te6 (spin-phonon coupling) and Bi2Te3-xSex (phonon-phonon coupling). Cr2Ge2Te6 is one of the rare class of ferromagnetic semiconductors and recent thermal transport studies suggest the spin and lattice are strongly coupled in its cousin compound Cr2Si2Te6. In this work, the spin-phonon coupling in Cr2Ge2Te6 has been revealed in multiple ways: we observed a split of two phonon modes due to the breaking of time reversal symmetry; the anomalous hardening of an additional three modes; and a dramatic enhancement of the phonon lifetimes. It is well-known that the phonon-phonon interaction plays a signicant role in determining the thermal transport properties of thermoelectrics. A comprehensive study of the phonon dynamics of Bi2Te3-xSex has been performed. We found that the unusual temperature dependence of dierent phonon modes originates from both cubic and quartic anharmonicity. These results are consistent with the resonance bonding mechanism, suggesting that the resonance bonding may be a common feature for conventional thermoelectrics. In the Raman spectra of Bi2Te2Se, the origin of the extra Raman feature has been debated for decades. Through a temperature dependent Raman study, we were able to prove the feature is generated by a Te-Se antisite induced local mode. The anomalous linewidth of the local mode as well as the anharmonic behavior were explained through a statistical analysis. Then, a wavelet transform and data clustering based spike-removal algorithm is proposed to resolve the erroneous spikes caused by cosmic rays in Raman spectra. Data sets from real measurements were analyzed to demonstrate the capability of the algorithm. Finally, the results of a minor project are presented. Thin lms of the high dielectric material SrTiO3 grown via a new method on silicon(100) are studied by ellipsometry. The results suggest that two layers of SrTiO3 are formed during the growth.

Keywords: Anharmonicity
Many body interaction
Raman
Spin-phonon coupling
Wavelet
Advisor: Burch, Kenneth S.
Crosstalk between CX3CL1 and the Cytoskeleton during Vascular Inflammation

The ability of the cortical actin cytoskeleton to regulate the lateral diffusion of plasma membrane molecules is a fundamental guiding principle underlying many cellular processes. By creating and stabilizing diffusional barriers, the cytoskeleton can precisely regulate the association or dissociation of molecules in both time and space, ultimately dictating the signalling output of a cell. In this dissertation, I explore how modulation of the cortical actin cytoskeleton contributes to two critical aspects of vascular inflammation. Initially in Chapter 2, I focus specifically on endothelial cells and the unique transmembrane chemokine, CX3CL1, which is strongly implicated in the recruitment of leukocytes to the vascular intima and the progression of atherosclerosis. I document a novel cytoskeletal regulatory mechanism that limits the interactions between CX3CL1 and the membrane-associated protease ADAM10, thereby controlling the proteolytic release of soluble chemokine. Moreover, I discuss the implications of this mechanism in the recruitment of leukocytes during atherosclerosis, as well as the implications for membrane protease-substrate interactions in general. In Chapter 3, I explore how the proteolytically released, soluble species of CX3CL1 can subsequently influence the macrophage cytoskeleton and feed-forward to enhance the lateral diffusion and clustering of the scavenger receptor CD36. Consequently, CD36 more readily engages and internalizes cholesterol-rich, oxidized low-density lipoproteins, leading to the accumulation of cholesterol esters within macrophages, and thus, the acceleration of foam cell formation. These findings reveal a novel function of chemokines in priming macrophages for the engagement of multivalent ligand. Taken together, the body of work described in this dissertation emphasizes the role of the cytoskeleton in tuning cellular responses and demonstrates how cytoskeletal dysregulation can contribute to the progression of inflammation.

Keywords: Atherosclerosis
Cytoskeleton
Receptors
Signal integration
Single-molecule imaging
Vascular inflammation
Advisor: Robinson, Lisa
Eco-labeling and the Conditions for Rigorous and Credible Transnational Governance

Eco-labeling schemes now exist in nearly every country on Earth and are gaining traction with some of the world’s largest companies. However the rigour and credibility of these schemes varies widely. Whereas some eco-labeling organizations (ELOs) adhere to best practices designed to increase the likelihood that their schemes will be rigorous and credible, others do not. In this dissertation, I explain variation in the level of adherence to best practices amongst transnational eco-labeling organizations using a two-phased mixed-method research design. In the first phase, I build and analyze an original dataset comprising information on the policies and practices of 123 transnational ELOs. In the second phase, I build on my statistical findings by further investigating both deductive and abductive hypotheses in the context of two representative case studies, sustainable aquaculture and carbon labeling. My central argument is that who an eco-labeling organization targets for governance holds a strong relationship to its propensity to follow best practices. Specifically, ELOs that “aim big” – meaning those that target a large proportion of a relevant global market – are more likely to follow best practices than those with narrower ambitions. “Aiming big” subjects ELOs to heightened critical scrutiny, increases demand for democratic legitimacy, and over time, augments their organizational capacity. These three conditions, in turn, drive attention to best practices and help create rigorous and credible eco-labels with a better chance of meeting environmental objectives. This dissertation contributes in several ways to scholarship on private authority and global governance. First, it suggests that renewed scholarly attention be directed towards the targets of governance, since pressure towards procedural rigour often comes from the governed community and not the owners of a governance scheme. Second, it argues that there is no unitary pathway to rigorous and credible governance; different causal mechanisms and multiple behavioral logics are operative in steering ELOs towards increased best practice adherence. Lastly, it holds implications for policy by suggesting that ELOs should purposively seek global presence and target large businesses when seeking to maximize their environmental impacts.

Keywords: Best practices
Credibility
Eco-labeling
Environmental governance
Transnational governance
Advisor: Bernstein, Steven
Identification of Genetic Polymorphisms that Promote Autoimmunity on New Zealand Black (NZB) Chromosome 1 and their Mechanisms of Action

Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of autoantibodies and the development of an immune complex-mediated glomerulonephritis (GN). The New Zealand Black (NZB) mouse is considered to be an excellent model of SLE. Identification of susceptibility loci and the mechanisms through which they act to produce autoimmunity has been greatly aided by the study of congenic mouse strains, in which homozygous intervals containing these loci have been introduced onto a non-autoimmune B6 genetic background. Genetic loci on NZB chromosome (c) 1 lead to antinuclear antibody (ANA) production and glomerulonephritis (GN). Previously our laboratory showed that mice with a homozygous NZB 70 to 100 cM c1 interval introgressed onto the B6 background develop fatal GN. Using a series of congenic mice with shorter NZB c1 intervals, the laboratory has demonstrated that there are at least three lupus susceptibility loci located within this region that are sufficient to lead to high titer anti-nuclear auto-antibody production and severe life-threatening GN. In this thesis I have sought to further characterize the cellular abnormalities and identify the genetic polymorphisms that produce the phenotype in c1(70-100)mice. In the second chapter, I have characterized the immune functional defects associated with the severity of disease in a series of sub-congenic mice with shorter intervals derived from this mouse strain. I showed that the severity of renal disease parallels expansion of Th1, Th17, and Tfh pro-inflammatory cell subsets. I also demonstrate that expansion of these cell subsets results from altered T cell and dendritic cell functional abnormalities, which is a consequence of interactions between at least 3 independent genetic loci. Next, I sought to identify the genetic polymorphism that leads to altered dendritic cell function in NZB chromosome 1 congenic mice. In chapter 3, I provide evidence suggesting that a polymorphism in EAT-2 leads to reduced levels of expression of this molecule in NZB c1 congenic mice, resulting in increased levels of cytokine secretion by myeloid DC that support expansion of pathogenic T cell subsets.

Keywords: autoimmunity
Dendritic cells
Genetic
Lupus
Mouse model
T cells
Advisor: Wither, Joan
Rethinking 'Historical Mysticism' in the Age of Russian Realism

The events of the 1850s and the early 1860s, including the Emancipation of the serfs (1861) and the Millennium celebration of Russia (1862), became a turning point in the cultural relationship between educated society and the narod. Following a wave of disturbances in the Russian countryside at that time, some Russian intellectuals came to perceive the narod as a protagonist in the political, social and cultural life of the Empire. These disturbances also revealed the narod’s tendency to interpret historical developments through a certain mythological framework. This dissertation argues that the public attention to the narod in the aftermath of these events raised educated society’s awareness of the political attitudes and historical thinking of the narod expressed though its mythology. I discuss how historians, writers and journalists such as Sergei Solovyov, Daniil Mordovtsev, Fyodor Dostoevsky, Mikhail Saltykov-Shchedrin, Mikhail Pogodin, and Lev Tolstoy reimagined and redefined the narod through its penchant for mysticism. For these thinkers, understanding the narod, its beliefs and ideals, and how it conceptualized history became a prerequisite for shaping the image of the national and ideological nucleus of the Russian Empire. Chapter I of this dissertation examines how, under which historical circumstances, and why the interest in popular mythology among educated society emerged in the two reform decades (the 1850s-1860s); what it revealed about the political views of the narod, and how politics shaped it; which specific aspects of it were frequently utilized and discussed in the print media and to what end; and how a new debate with the concept of the narod and folk mysticism as its center of gravity evolved in Russia. Chapter II discusses Lev Tolstoy’s approach to folk mysticism in his novel War and Peace. I argue that the novelist makes a commune of peasants, whose actions and choices are driven by profound mythological beliefs, an agent of a single collective will. Chapter III demonstrates how in his A History of a Town, Mikhail Saltykov-Shchedrin problematizes mythological beliefs that inform collective behaviour of the narod, considering them to be a stumbling block for the narod’s own historical development and that of the country. Chapter IV discusses how the mythological framework of the narrative of The Possessed by Fyodor Dostoevsky absorbs a popular eschatological vision and becomes instrumental for the writer to express his social critique of modernity. This study demonstrates how in their literary works, the three authors show the existence of the narod not on the cultural periphery of the Russian Empire, but within the socio-political landscape, linking the narod’s moral image to its sacred beliefs and ideals. At the same time I argue that each of them utilizes popular mythology as an allegorical language to communicate his social and political ideas.

Keywords: Dostoevsky
popular mythology
Saltykov-Shchedrin
the narod
The Russian Empire
Tolstoy
Advisor: Orwin, Donna
Precarious Work in Montreal: Women, Urban Space, and Time

This dissertation examines the impact of precarious work on women in Montreal. Precariousness is increasingly common in Quebec, where women are overrepresented in part-time, temporary, and self-employed work. Based on three years of fieldwork, the thesis argues that while many women experience precariousness in the labour market, they do not experience it in the same ways. The neighbourhoods in which women live significantly shape their lives at work and home. Building critically on the literature on precariousness and social class, my research theorizes precarious workers as members of the working class, not as a marginalized social class outside it. Specifically, the dissertation asks how urban space influences precarious work and how time pressures impact experiences of work and home. First, while noting that precarious workers across industries (e.g. art, teaching, service) face housing pressures similar to those experienced by other members of the working class, the research shows that precarious women workers living in central neighbourhoods are especially at risk of being displaced by the middle-class. Second, the project brings important attention to paid and unpaid domestic work. Most research in the field of “time-use” at work focuses on sectors outside the home, even though women have long performed unwaged housework and many women continue to undertake paid employment or self-employment in the home. The dissertation demonstrates the ways in which women’s workloads have increased in the sphere of the home, diminishing their physical health and rendering them more precarious. Third, with reference to women who continue to perform large amounts of unpaid work, the research considers the relevance of historical and contemporary debates around the relationship between paid and unpaid labour, illustrating how women’s wages are negatively impacted by this unpaid work. This dissertation brings together the social dimensions of gender, race, social class, and urban space. In so doing, the project contributes a multi-scalar analysis to antiracist feminist political economy and reaffirms the importance of social class within feminist geography. Bridging these two broader traditions – political economy and economic geography – the project provides a critical framework for understanding the specificities of precarious work for women in Montreal.

Keywords: class
gender
Montreal
precarious work
race
Advisor: Goonewardena, Kanishka
Musical Assemblies: How Early Christian Music Functioned as a Rhetorical Topos, a Mechanism of Recruitment, and a Fundamental Marker of an Emerging Christian Identity

This dissertation examines the various ways in which early Christ-followers incorporated music into their religious discourse and ritual practice. Scholars have primarily focused on two particular areas of inquiry: the cultural and religious 'origins' of early Christian music and the history of music within the context of church liturgy. Music, however, played a much greater role within Christian assemblies than simply existing as part of religious liturgy. I contend that music helped shape an emerging Christian identity within early Christ-following assemblies and collective singing became a vital component in defining in-group and out-group boundaries. Early Christian writings also demonstrate that hymn compositions were used as pedagogical tools, rhetorical devices, and mechanisms of recruitment to attract new members. I begin by examining Greco-Roman and Jewish primary source materials that reference or describe the nature of musical practice in antiquity in order to contextualize my study of musical references in early Christian texts. The next section utilizes recent developments in cognitive science to illustrate the importance of collective singing in establishing a group identity, creating cohesive social bonds, and evoking particular emotional responses. I apply this methodological approach, along with a socio-historical lens, to a variety of early Christian texts in order to argue that collective singing functioned as a critical medium in which early Christian authorities formulated their identity and defined the boundaries of 'correct' and 'incorrect' religious thought and practice. The melodies and lyrics used by some assemblies functioned as a rhetorical medium to denounce out-group theologies and practices while simultaneously operating as an instrument of recruitment. This study concludes that collective singing played a previously unidentified role in the success of early Christianity as a social movement through mechanisms of identity formation, social bonding, and recruitment of new members.

Keywords: Cognitive Science of Religion
Heresy
Identity
Liturgical History
Orthodoxy
Recruitment
Advisor: Kloppenborg, John S