VictorJuiz/thesis huggingface dataset:
Detection of Apoptosis using Magnetic Resonance Imaging: Relaxation in the Presence of Gadolinium and Magnetization Transfer Studies

Imaging techniques provide a method for non-invasive longitudinal monitoring of cancer therapies, but common metrics such as tumour size are late markers and do not indicate heterogeneity of response. Apoptotic cell death is an earlier marker of tumour response and produces molecular and cellular-level changes (macromolecular breakdown, membrane changes and cell shrinkage) that may be detectable by magnetic resonance imaging (MRI). Previous studies using conventional MRI methods have shown little sensitivity to apoptosis. In this thesis it is hypothesized that, using an extracellular contrast agent to affect the MRI property of relaxation for extracellular water preferentially, parameters related to water in the intracellular and extracellular environments and the exchange between them can be obtained and will be sensitive to apoptosis. It is also hypothesized that membrane changes and macromolecular breakdown are detectable by the technique of magnetization transfer. Measurements of relaxation in the presence of contrast agent in vitro demonstrated a decrease in extracellular water fraction and an increase in the rate of water exchange across the plasma membrane during apoptosis. In vivo, this method was complicated by the difficulty of delivering contrast agent to the tumour, but regions with good delivery showed correlation between high water exchange rates from MRI and apoptosis in histology. Magnetization transfer studies indicated only small changes in vitro during apoptosis and these were largely related to changes in the free water, so this method was not investigated further. Further work is required to determine the tumour lines where the water exchange methods may be applied reliably. Nevertheless, the method of measuring water exchange presented in this thesis can be performed in a clinically-feasible amount of time (~20 minutes). It therefore has potential in detecting apoptosis and predicting therapy response. It also emphasizes the role of water exchange in conventional MRI relaxation experiments.

Keywords: MRI
apoptosis
cancer therapy response
water exchange
magnetization transfer
relaxation
Advisor: Stanisz, Greg
Natural and Cultural Landscape Evolution during the Late Holocene in North Central Guatemalan Lowlands and Highlands

Paleoecology has been only in recent decades applied to Mesoamerica; this thesis provides new records of paleoenvironmental changes in Guatemala. Paleoecological reconstructions are developed based mainly on pollen in the Lachuá lowlands and Purulhá highlands of the Las Verapaces Region. For the first time, quantitative vegetation and climate analyses are developed, and plant indicator taxa from vegetation belts are identified. Changes in vegetation are explained partially by elevation and climatic parameters, topography, drainage divides, and biogeography. Pollen rain and indicator plant taxa from vegetation belts were linked through a first modern pollen rain analysis based on bryophyte polsters and surface sediments. The latter contain fewer forest-interior plant taxa in both locations, and in the highlands, they contain higher local pollen content than in the lowlands. These calibrations aided vegetation reconstructions based on fossil pollen in sediment records from the Lachuá and Purulhá regions. Reconstructions for the last ~2000 years before present (BP) were developed based on fossil pollen from cores P-4 on a floodplain in Purulhá, and L-3, a wetland in Lachuá. Core P-4 suggests that Mayan populations developed a system of agricultural terraces in a former paleolake-swamp environment, which was abandoned at the time of the Spanish Conquest (~400 BP). Core L-3 indicates the abandonment of Mayan “Forest Gardens” at the time of the early Postclassic. These gardens likely prevailed during the Classic period (~300-1100 yrs BP) at the outskirts of the ancient city of Salinas de los Nueve Cerros. Following abandonment, forest recovery took place for about 800 yrs. Cultural factors are found to be more important in determining vegetation dynamics in this region, since no clear evidence of climate forcing was found. The P-4 and L-3 cores provide likely evidence that Mayan populations were, contrary to other evidence, innovative landscape managers. Scenarios in the Las Verapaces Region have been drastically modified in recent times (e.g. after the European Conquest), as suggested by pollen evidence in the top of both P-4 and L-3 cores, possibly due mostly to modern large scale natural resources exploitation, which represent environmental threats greater than any seen in the last ca. 2000 years.

Keywords: Lachua
Purulha
Salinas de los Nueve Cerros
Cahabon River
pollen
LOI
Mayan Forest Garden
Agricultural terraces
Mesoamerica
Advisor: Cowling, Sharon A.
Finkelstein, Sarah A.
Occupational Exposures and the Co-occurrence of Work-related Skin and Respiratory Symptoms

Occupational skin and respiratory symptoms, and disease, are common problems. Workers can develop new disease or aggravate existing disease as a result of exposures at work. Many workers are exposed to chemicals that can cause both respiratory and skin responses and there is evidence that some workers experience symptoms in both systems. There is also evidence that skin exposure may lead to sensitization and the development of respiratory disease. There is very little research that has examined both airborne and skin exposures together with lung and skin outcomes. The purpose of this thesis was to further investigate the relationships between occupational exposures, skin symptoms and disease, and respiratory symptoms and disease. Four studies were undertaken to improve our understanding of these complex relationships. Results from a study of clinical patch test data determined that seven of the ten most common occupational contact allergens are also capable of causing occupational asthma and that these common occupational exposures may not be recognized as sensitizers in common reference materials. Exposure-response relationships for skin symptoms were modeled in bakery workers and auto body shop workers using historical data; significant exposure-response relationships were found for auto body workers. In two separate studies of concurrent skin and respiratory symptoms, workers did report concurrent skin and respiratory symptoms. In predictive models, subjects reporting a history of eczema were more likely to report concurrent skin and respiratory symptoms. Overall, the results from this thesis provide more evidence that the skin and respiratory systems are associated. This body of work suggests that: (1) several common occupational exposures can cause disease in both the skin and respiratory system; (2) a portion of workers report both skin and respiratory symptoms; and (3) exposure-response relationships do exist for skin symptoms, both work-related and non-work-related. Future studies need to gather detailed information about exposure and response in both systems in order to better determine the role of exposure(s) in the development of skin and respiratory symptoms. Improved understanding of these relationships will allow for more targeted and effective exposure prevention strategies and will ultimately reduce the burden of occupational disease.

Keywords: Respiratory symptoms
Skin symptoms
Occupational exposures
Advisor: Holness, Dorothy Linn
Are The[se] Kids Alright?: States of Incarceration and Subordination in the Learning and Lived Experiences of Youth in a Juvenile Detention Facility

This study examines the dynamics and implications of trans-spatial subordination in/across the lived experiences of six incarcerated participant youths in a secure custody facility for juveniles in Louisiana. Five male teenagers (four African American, one White) and one female teenager (African American) discuss the limitations, harassment, and confinement in various aspects of their lives and speak about the impact on their expectations for the future. The author employs several methodologies in order to develop a multimedia, multifaceted representation of their lives. The narratives elicited through interviews provide the bulk of the data as the participants describe this perpetual subordination. The photographs, resulting from the implementation of a visual ethnographic methodology, provide images that serve as catalysts for introspection and analysis of significance in the mundane and routine, particularly as they apply to the carceral facilities, structures, and policies themselves. Film viewing and discussion offer an array of depictions of youth and criminality to which the youths responded, granting a simultaneous peek at how these marginalized youths viewed themselves and how mainstream media productions depict them. After a particularly provoking viewing session of an animated film, the author expands the preliminary boundaries of the work beyond cells and the walls of the prison. The expanding focus examines subordinating elements in their lives with their families and in their neighbourhoods. The challenges, harassment, and obstacles experienced in their communities continued in their schools and during their encounters with law enforcement, the latter of which often led directly to imprisonment. Finally, the youths reflected on the confining subordination that existed in the facilities, the product of the combination of: their discomfort with the surveillant structure, their perceived arbitrariness of privilege, and the lack of any relevant education. They also identified opportunities for voicing their opinions and recognized the relative safety of this facility compared to others. As the participants conceptualized their futures and articulated their relatively narrow and often ambiguous hopes, the sobering influence of such perpetual subordination is evident. The author closes with a discussion of the study’s importance to future research with marginalized youth in a society of increasing surveillance and security as well as implications for teacher education.

Keywords: subordination
incarcerated youth
educational access
visual ethnography
narrative
Advisor: Cooper, Karyn
More than a Metabolite: An Evaluation of the Potential Role of L-serine-O-phosphate as the Endogenous Agonist for the Group III Metabotropic Glutamate Receptors

The Group III metabotropic glutamate receptors (mGluR) are located presynaptically on axon terminals and act as autoreceptors and heteroreceptors by inhibiting neurotransmitter release. Much has been learned about these receptors through exogenous application of L-serine-O-phosphate (L-SOP), an endogenous amino acid derivative and known activator of the Group III mGluRs. We hypothesized that L-SOP is the endogenous co-agonist at the high affinity Group III mGluR, mGluR4. We found the EC50 of L-SOP at mGluR4 was 0.5 μM, and determined that the concentration of L-SOP in whole brain was approximately 5 μM. An immunocytochemical survey revealed that cells containing the enzymatic machinery necessary for L-SOP synthesis and metabolism were observed in two brain regions known to express mGluR4, namely, cerebellum and hippocampus. In the cerebellum, the L-SOP synthetic and metabolic enzymes were found in Bergmann glia and Purkinje cells, two cells which form a tripartite synapse with parallel fiber axon terminals where the mGluR4 subtype is exclusively expressed at high levels. In the hippocampus, the L-SOP metabolic enzyme was detected in young neurons emanating from the neurogenic subventricular zone. Attempts to raise endogenous levels of L-SOP by crippling the L-SOP metabolizing enzyme (phosphoserine phosphatase), over-expressing the L-SOP synthesizing enzyme (phosphoserine aminotransferase), or through dietary protein restriction, to study the effects on neurotransmission and neurodevelopment in the central nervous system (CNS) were unsuccessful, suggesting that the production of L-SOP remains stable despite manipulation of the synthetic and metabolic enzymes. Finally, the ability of L-SOP to modulate glutamate release from presynaptic terminals was examined in cerebellar synaptosomes. Co-incident activation of presynaptic mGluR4 and presynaptic GABAA receptors facilitated glutamate release, suggesting that simultaneous activation of parallel fibers and Bergmann glia may serve to enhance synaptic transmission. This observation expands the traditional view of Group III mGluRs acting solely as inhibitory autoreceptors. Taken together, these results provide compelling evidence to support the hypothesis that L-SOP is the endogenous agonist at mGluR4, and possibly other Group III mGluRs.

Keywords: Bergmann Glia
metabotropic glutamate receptors
L-serine-O-phosphate
L-serine
Cerebellum
Parallel fiber
GABA-A
mGluR4
L-SOP
Glutamatergic neurotransmission
Advisor: Hampson, David R.
Mining User-generated Content for Insights

The proliferation of social media, such as blogs, micro-blogs and social networks, has led to a plethora of readily available user-generated content. The latter offers a unique, uncensored window into emerging stories and events, ranging from politics and revolutions to product perception and the zeitgeist. Importantly, structured information is available for user-generated content, by dint of its metadata, or can be surfaced via recently commoditized information extraction tools. This wealth of information, in the form of real-world entities and facts mentioned in a document, author demographics, and so on, provides exciting opportunities for mining insights from this content. Capitalizing upon these, we develop Grapevine, an online system that distills information from the social media collective on a daily basis, and facilitates its interactive exploration. To further this goal, we address important research problems, which are also of independent interest. The sheer scale of the data being processed, necessitates that our solutions be highly efficient. We propose efficient techniques for mining important stories, on a per-user-demographic basis, based on named entity co-occurrences in user-generated content. Building upon these, we propose efficient techniques for identifying emerging stories as-they-happen, by identifying dense structures in an evolving entity graph. To facilitate the exploration of these stories, we propose efficient techniques for filtering them, based on users’ textual descriptions of the entities involved. These gathered insights need to be presented to users in a useful manner, via a diverse set of representative documents; we thus propose efficient techniques for addressing this problem. Recommending related stories to users is important for navigation purposes. As the way in which these are related to the story being explored is not always clear, we propose efficient techniques for generating recommendation explanations via entity relatedness queries.

Keywords: algorithms
data mining
information retrieval
user-generated content
Advisor: Koudas, Nick
A Qualitative Study of the Process of Acculturation and Coping for South Asian Muslim Immigrants Living in the Greater Toronto Area (GTA)

The present study explores the nature of coping mechanisms among South Asian Muslim immigrants living in the Greater Toronto Area (GTA) who have been living in Canada between three to five years and experienced acculturation challenges and depression. Thirteen immigrants (seven females and six males) were interviewed to share their stories of personal experiences of settlement and acculturation in Canada. These interviews were analyzed using the grounded theory approach to develop themes and sub-themes to understand and interpret the data. The findings reveal that the research participants experienced a number of acculturation challenges (feeling different, feeling excluded, disruption in the family and material differences) which led to depression. During the course of their depression participants experienced certain events which became turning points in their lives, subsequently motivating them to change the way in which they live. They sought out particular kinds of support and coping mechanisms which helped them to settle, integrate and belong to the Canadian culture. The midlevel grounded theory that has emerged from participants’ responses is discussed. Recommendations are made to inform mental health professionals to incorporate these coping mechanisms in delivering culturally sensitive services to the target population. Study implications for theory, psychotherapy, counselling and other mental health practices and future research in the area of settlement and adaption of newcomers in Canada are discussed.

Keywords: acculturation
South Asians
Muslims
immigrants
depression
coping
Advisor: Moodley, Roy
Development of an Endothelial Cell Niche in Three-dimensional Hydrogels

Three-dimensional (3D) tissue models have significantly improved our understanding of structure/function relationships and promise to lead to new advances in regenerative medicine. However, despite the expanding diversity of 3D tissue fabrication methods, in vitro approaches for functional assessments have been relatively limited. Herein, we describe the guidance of primary endothelial cells (ECs) in an agarose hydrogel scaffold that is chemically patterned with an immobilized concentration gradient of vascular endothelial growth factor 165 (VEGF165) using multiphoton laser patterning of VEGF165. This is the first demonstration of this patterning technology to immobilize proteins; and the first demonstration of immobilized VEGF165 to guide endothelial cell growth and differentiation in 3D environments. It is particularly compelling that this 3D hydrogels provide an excellent biomimetic environment for stem cell niche, thereby offering a new approach to study stem cell biology. In this thesis, we focused on the retinal stem cell niche, investigating cellular interactions between retinal stem and progenitor cells (RSPCs) and endothelial cells (ECs). By using this 3D in vitro model, we demonstrated the synergistic interactions between RSPCs and ECs wherein RSPCs migrated into 3D gels only in the presence of ECs and RSPCs stabilized EC tubular-like formations. Moreover, we characterized the contact-mediated effects of ECs on RSPC fate in terms of proliferation and differentiation.

Keywords: tissue engineering
3D hydrogels
Endothelial Cell
Retinal Stem and Progenitor Cell
Advisor: Shoichet, Molly
GATA4 Represses Formation of Glioblastoma Multiforme

The GATA transcription factors consist of six family members that bind the consensus DNA binding element W-GATA-R, and are poorly characterized in the central nervous system (CNS). In this thesis we identify GATA4 to be expressed in the neurons and glia of normal murine and human embryonic and adult CNS with significant loss in Glioblastoma Multiforme (GBM). GBM is the most common and lethal primary brain tumour and exhibits multiple molecular aberrations. Here we report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumour suppressor gene. Although GATA4 was expressed in normal brain, loss of GATA4 was observed in GBM operative samples and was a negative survival prognostic marker. GATA4 loss occurred through promoter hypermethylation or novel somatic mutations. Loss of GATA4 in normal human astrocytes promoted high-grade astrocytoma formation, in cooperation with other relevant genetic alterations such as activated Ras or loss of TP53. Loss of GATA4 with activated Ras in normal astrocytes promoted a progenitor like phenotype, formation of neurospheres and the ability to differentiate into astrocytes, neurons and oligodendrocytes. Re-expression of GATA4 in human GBM cell lines, primary cultures and brain tumour initiating cells suppressed tumour growth in vitro and in vivo through direct activation of the cell cycle inhibitor P21CIP1, independent of TP53. Re-expression of GATA4 also conferred sensitivity of GBM cells to temozolomide, a DNA alkylating agent currently used in GBM therapy. This sensitivity was independent of MGMT, the DNA repair enzyme often implicated in temozolomide resistance. Instead GATA4 reduced expression of APNG, a DNA repair enzyme poorly characterized in GBM mediated temozolomide resistance. Identification and validation of GATA4 as a tumour suppressor gene and its downstream targets in GBM may yield promising novel therapeutic strategies.

Keywords: GATA4
Glioblastoma Multiforme
Advisor: Guha, Abhijit
Mahatma Gandhi and Martin Luther King, Jr. in the 21st Century: The Pedagogical Possibilities and Limitations for Transformative Education

The current trend of global violence and their impact on families and communities as well as the field of university education is scary for a society that is struggling with this false sense of apathy and complacency. How did the ordinary people get seduced to the idea that there is no way out of this global assault? How then do we extricate ourselves from this “tortured consciousness” (Asante, 2007) and this false sense of “nihilism” (West, 1994) and recoup this “incommensurable loss” (Simmons, 2010) to global violence? Even more crucial, where is the place of education in retrieving this incommensurable loss while providing hope and possibility for a better future? Provoked by the desire to have answers to these questions, the dissertation relies on the knowledge and experiences of twenty qualitatively selected university activists and existing literature to critically examine the non-violent praxes of Gandhi and King, Jr. and their pedagogical implications for transformative university education. The dissertation further draws on the knowledge of Frantz Fanon and Malcolm X to bring complex and nuanced readings to violence and non-violence. The dissertation notes that violence and non-violence are not mutually exclusive as already known. The dissertation also notes that while resistive violence may be justified, it does not necessarily guarantee true transformation, reconciliation, and healing. Instead, love, humility, truth, dialogue, non-violent direct action, discipline, and spirituality are salient in achieving true transformation in university activism. The dissertation further observes that educational activism is more than walking on the street with placards to protest against institutional violence. Sometimes, the secret activism that is done strategically within the corridors of power can achieve more far-reaching results than the open protest against power on the street. The dissertation concludes with six key non-violent strategies that can help in social and political mobilization of university students for transformative university education.

Keywords: Non-Violence
Violence
Pedagogy
Ahimsa
Satyagraha
Mahatma Gandhi
Martin Luther King Jr
Frantz Fanon
Antiracism
Anti-colonialism
Love
Spirituality
Advisor: Dei, George Jerry Sefa