VictorJuiz/thesis huggingface dataset:
Hydrological, Biogeochemical and Landscape Controls on Mercury Distribution and Mobility in a Boreal Shield Soil Landscape

Mercury (Hg)-contaminated freshwater fisheries are a global toxicological concern. Previous research suggests that the slow release of Hg in runoff from upland soils may delay the recovery of Hg-contaminated aquatic systems. Four complementary studies were undertaken in a small boreal Shield headwater catchment as part of the Mercury Experiment to Assess Atmospheric Loading in Canada and the U.S. (METAALICUS) to assess the controls on the retention and release of historically-deposited Hg (ambient Hg) and newly-deposited (spike Hg) in the soil landscape. In the first study, hydrometric and GIS-based methods were used to quantify thresholds in terrestrial water storage and their relationship to observed rainfall-runoff response. It was found that event-scale hydrologic response displayed a threshold relationship with antecedent storage in the terminal depression and predictions of event runoff improved when storage excesses from upslope depressions were explicitly routed through the catchment. In the second study, it was shown that the dominant source of ambient Hg to the lake was likely derived from shallow soil-water flowing through the lower, well-humified organic soil horizon. Throughout the catchment, ambient Hg to soil organic carbon (SOC) ratios increased with depth and the experimentally-applied spike Hg was concentrated in the surface litter layer, suggesting that the vertical redistribution of Hg in the soil profile is a function of the rate of decomposition of SOC. In the third study, canopy type was found to be a good predictor of ambient Hg and spike Hg stocks in the lower organic horizon, while drainage conditions were not, suggesting that vertical fluxes of Hg dominate over lateral fluxes in topographically-complex landscapes. Lastly, it was shown that catchment discharge, antecedent depression storage and antecedent precipitation were the best predictors of dissolved organic carbon (DOC), ambient Hg and spike Hg concentrations in catchment runoff. A comparison of DOC, ambient Hg and spike Hg dynamics for two storm events showed that distinct shifts occurred in the concentration-discharge relationship as a result of differences in antecedent moisture conditions. Combined, the results of the four studies demonstrate the need to incorporate hydrological, biogeochemical and landscape controls into predictive models of terrestrial-aquatic Hg export.

Keywords: catchment hydrology
mercury biogeochemistry
Advisor: Branfireun, Brian
Circuit Performance Verification and Optimization in the Presence of Variability

The continued scaling of digital integrated circuits has led to an increasingly larger impact of process, supply voltage, and temperature (PVT) variations. The effect of these variations on logic cell and interconnect delays has introduced challenges to both circuit performance (timing)verification and optimization. In order for us to fully take advantage of the benefits of technology scaling, it is essential that ``variation-aware''techniques for performance verification and optimization be developed and used in modern design flows. In this thesis such techniques for both performance verification and optimization are presented. First, we present a fast method for finding the worst-case slacks over all process and environmental corners. This method uses the standard set of PVT corners available in industry, and provides large runtime gains while maintaining a high degree of accuracy. After that, we propose an efficient block-based parameterized timing analysis technique that can accurately capture circuit delays at every point in the parameter space, by reporting all paths that can become critical. This method employs parameterized static timing analysis (PSTA) variability models, and allows one to easily examine local robustness to parameters in different regions of the parameter space. Next, we introduce an optimization method that alters clock network lines so that a circuit meets its timing constraints at all PVT settings under PSTA variability models. This is formulated as a Linear Program (LP), which is based on a clock skew optimization formulation, and as a result it can be solved efficiently. Finally, we present a method that uses characterized, pre-silicon, PSTA variational timing models to identify speedpaths that can best explain the observed delay measurements during silicon debug. This is a crucial step, required for both ``fixing'' failing paths and for accurate learning from silicon data.

Keywords: Digital Circuit Performance, Process Variations, Computer-Aided Design
Advisor: Najm, Farid N.
Global Analysis of Gene Expression in the Developing Brain of Gtf2ird1-/- Mice

Williams-Beuren Syndrome (WBS) is an autosomal dominant neurodevelopmental disorder caused by hemizygous deletion of a 1.5 Mb region on chromosome 7q11.23. Symptoms are numerous and include behavioural and cognitive components. One of the deleted genes, GTF2IRD1, a putative transcription factor, has been implicated in the neurological features of WBS by studying patients with atypical deletions of 7q11.23. Gtf2ird1-targeted mice have features consistent with the WBS phenotype, namely reduced innate fear and increased sociability. To identify neural targets of GTF2IRD1, microarray analyses were performed comparing gene expression in whole brains of Gtf2ird1-/- and wildtype (WT) mice at embryonic day 15.5 and at birth. Overall, the changes in gene expression in the mutant mice were not striking, with most falling in the range of 0.3 to 2 fold. qRT-PCR was used to verify the expression levels of candidate genes and examination of verified genes revealed that most were located on chromosome 5, within 50 Mb of Gtf2ird1. Expression of these candidate genes in Gtf2ird1-/- mice was found to be the same as in WT 129S1/SvImJ mice, indicating the differences were the result of flanking chromosomal material from the, 129-derived, R1 ES cells from which the Gtf2ird1-/- mice were generated, and that expression differences were unrelated to Gtf2ird1 dosage. Further analysis found that while many genes showed decreased expression using primers targeting the 3’ UTR, expression of upstream exons was not affected. Transcripts using alternative polyadenylation sites were identified using 3’ RACE, and qRT-PCR showed that expression of different 3’ UTR isoforms can occur in a strain specific manner. Expression analysis of previously identified GTF2IRD1 targets also failed to demonstrate an in vivo effect. In summary, I was unable to find any in vivo neuronal targets of this putative transcription factor, despite its robust expression in the developing rodent brain.

Keywords: Williams-Beuren syndrome
Gtf2ird1
Advisor: Osborne, Lucy
Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies

The overall aim of my thesis is to gain insight into the cellular and molecular basis of the hierarchical organization of the human blood system, and how these normal development processes are subverted into leukemogenesis. To date, the major cellular classes that comprise human blood remain ill defined as rigorous clonal analysis required to define the self-renewal and lineage potential of single cells has not yet been performed. Here, identification CD49f as a novel marker of human HSC led to the ability to transplant single human HSC in NOD-scid IL2Rgc-/- mice. Loss of CD49f and Thy1 uniquely demarcated multi-potent progenitors (MPP) from HSC. The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision during lineage restriction from HSC. The validity of this model in the mouse has been questioned; however, little is known about the lineage potential of human progenitors. By clonally mapping the developmental potential of seven progenitor classes from neonatal cord blood and adult bone marrow, human multi-lymphoid progenitors (MLP) were identified as a distinct population of Thy1-/loCD45RA+ cells in the CD34+CD38- stem cell compartment that can give rise to all lymphoid cell types, as well as monocytes, macrophages and dendritic cells. This indicates that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. While non-genetic mechanisms govern cell-fate commitment and lineage specification, hematopoietic malignancies are often initiated by aberrant gene rearrangements that can subvert normal cellular processes. Full transformation requires the accumulation of multiple genetic lesions. Most tumours exhibit dramatic genetic heterogeneity downstream of the initiating oncogenic event and are composed of pockets of genetically distinct clonal subpopulations. However little is known of how diversity evolves or the impact diversity has on functional properties. Here, using xenografting and DNA copy number alteration (CNA) profiling of human BCR-ABL1 lymphoblastic leukaemia, it was demonstrated that genetic diversity occurs in functionally defined leukaemia-initiating cells (L-IC) and that many diagnostic patient samples contain multiple genetically distinct L-IC subclones. Reconstructing the subclonal genetic ancestry of several samples by CNA profiling demonstrated a branching multi-clonal evolution model of leukaemogenesis, rather than linear succession. For some patient samples, the predominant diagnostic clone repopulated xenografts, while in others it was outcompeted by minor subclones. Reconstitution with the predominant diagnosis clone was associated with more aggressive growth properties in xenografts, deletion of CDKN2A/B, and a trend to poor patient outcome. Our findings link clonal diversity with L-IC function and underscore the importance of developing therapies that eradicate all intratumoural subclones.

Keywords: hematopoiesis
leukemia
Advisor: Dick, John E.
Holistic Education: The Flow and Pulse of Learning

Situated in the holistic education field, this research explores the mind/body experiences of six youth who remained in a drama group from the time they were children to their late adolescence. In the first phase of this research these participants reflected on their experiences of the imagination, thought and felt sensation as they engaged in meditation and mind/body warm-up exercises during the drama years. The participants applied their understanding of mind/body awareness to a question posed by Vivian Darroch-Lozwoski; what happens when we attend to nature feelingly? Over the course of one year, the youth explored the above question, individually and collectively through dreaming, reveries, the imagination, experiences of energy and as they wandered in nature. The inquiry directly addresses the existential, ontological and epistemological implications of holistic mind/body development and outlines approaches for gentling the mind and body to nature.

Keywords: Holistic Education
Eco-Spirituality
Depth Psychology
Youth
Phenomenology
Advisor: Miller, John P.
Cognitive Abilities Underlying the Bilingual Advantage in Set Shifting

Prior research has demonstrated that bilinguals outperform monolinguals on tasks requiring set shifting – that is, the ability to shift between different ways of thinking about an object or situation. For example, bilingual children have been shown to outperform monolingual controls on false-belief tasks and on the Dimensional Change Card Sort (DCCS) task. The present study aimed (a) to examine whether the bilingual advantage in false-belief and DCCS tasks can be replicated when accounting for languages/cultures and socio-economic status and (b) to determine whether inhibitory control, metarepresentation, and/or working memory underlie the advantage, if any exists. Three language groups (24 English monolingual, 24 French monolingual, and 24 English-French bilingual preschoolers) were tested on the following tasks: false-belief (FB) tasks, the DCCS task, an inhibitory control task (Stroop task), a metarepresentation task (Identity Statements task), a working memory task (Backward Word Span), and receptive language proficiency tests. Socio-economic status was measured through a parental questionnaire containing questions about parental income and education. Results showed that the three language groups were equivalent on socio-economic measures. Despite having significantly lower language proficiency scores, bilinguals’ raw scores on FB and DCCS tasks did not differ from monolinguals’ raw scores. After statistically controlling for language proficiency and age, bilinguals had significantly higher FB scores, but did not differ from monolinguals on DCCS scores. Analyses were then performed to determine whether inhibitory control, metarepresentation, and/or working memory help bilinguals “do more” in FB “with less” language proficiency. Working memory emerged as the likely candidate that compensates for the negative effect of bilingual children’s low language proficiency on FB performance because, after controlling for age and language proficiency, it was the only cognitive ability that fulfilled both criteria: (a) its measure correlated significantly with FB and (b) there was a bilingual advantage over both monolingual groups in the measure. A mediation analysis confirmed that the working memory measure significantly mediates the relation between bilingual status and FB while controlling for age and language proficiency. Both components of the working memory measure – that is, understanding of task instructions and maintenance/manipulation capacity – mediate this relation.

Keywords: bilingualism
theory of mind
executive functioning
working memory
Advisor: Astington, Janet
Development of Novel Cell Fate Control Gene Therapy for Applications in Cancer and Immune Disorders

Cellular therapies rely on the delivery of therapeutic cells into patients, but their safety can be compromised by the manipulation of cells ex vivo or their placement outside of their natural context in vivo. Cell Fate Control Gene Therapy (CFCGT) offers the possibility of establishing pharmacological controls over gene-modified cells (GMCs) with regards to their proliferation, differentiation, or function. In its simplest form, 'suicide' gene therapy (SGT), stable introduction of a 'suicide' gene that can activate a non-toxic prodrug establishes control over the survival of GMCs. Current SGT modalities are sub-optimal in clinical setting. To overcome the many limitation of current strategies, we have developed a next-generation CFCGT approach based on the active site-engineered variants of human deoxyCytidine Kinase (dCK), which enable robust activation of multiple Nucleoside Analogue (NA)-based prodrugs, act early in the pathway enabling rapid accumulation of activated NAs in target cells, and also provide the capabilities for the direct imaging of GMCs. Stable introduction of dCK variants into target cells by means of Lentiviral (LV) gene transfer significantly increases their sensitivity to multiple prodrugs. Our dCK variant with only two active site amino acid substitutions is expected to be non-immunogenic yet capable of specifically activating deoxythymidine- and deoxyuridine-based NAs that are not substrates for the wild-type enzyme, such as bromovinyldeoxyuridine (BVdU) and L-deoxythymidine (LdT). We show here that dCK can be used for controlling the survival of GMCs, in cell lines and primary cells in vitro and in a murine xenogeneic transplant models in vivo. To characterize dCK/prodrug-mediated killing mechanisms in GMCs, we have examined the levels of active metabolites in cells and the cellular pathways they antagonize. We describe here the experimental basis for the application of this novel CFCGT in bone marrow transplantation for management of Graft-versus-Host Disease (GvHD) and in enhancing chemotherapy in direct treatment of tumors. In summary, we have developed a novel and robust strategy for effective CFCGT that addresses the many shortcomings of existing modalities. Future studies will validate this novel system in a variety of primary cells and animal disease models, including models of hematopoietic transplantation and ES/iPS-based cell therapies.

Keywords: Gene Therapy
Cell Therapy
Lentiviral Vectors
GvHD
Allogeneic Transplantation
Cancer
Immunology
Advisor: Medin, Jeffrey A.
Climate Change in the Canadian Boreal Forest: The Effect of Warming, Frost Events, Cloud Cover and CO2 Fertilization on Conifer Tree Rings

Anthropogenic climate change is expected to dramatically affect boreal forests, not only through warming effects, but through changes in seasonal and diurnal temperature patterns, precipitation, cloud-cover, and direct effects of rising CO2. My doctoral research examines the impact of these changes on dominant boreal forest conifer species, using dendrochronological methods. Through my analysis of white spruce (Picea glauca) and lodgepole pine (Pinus contorta) tree rings across five Yukon Territory sites, I found that white spruce growth is showing growth declines in response to all three measured climate changes, with negative correlations between tree ring increment and spring and summer temperature, spring frost events, and growing season cloud cover. Lodgepole pine populations exhibited growth enhancement with increasing spring maximum daily temperatures, but generally neutral responses to warming summers, higher frost event frequency and increased cloud cover. To evaluate the effect of rising CO2 on boreal forest growth, I examined three representative managed forest stands across Canada, first building a model of climate effects, and examining temporal trends in the residual growth patterns. I found evidence for CO2 fertilization in Ontario black spruce (Picea mariana) and Manitoba white spruce populations, particularly at younger ages, but no growth enhancement in Yukon lodgepole pine. These results taken together suggest that Yukon white spruce may suffer pronounced growth declines under continued climate change, but more eastern spruce populations may be better able to benefit from increased carbon availability. Yukon lodgepole pine populations are less vulnerable to the impacts of climate change, but are also unlikely to exhibit significant growth increases in response to increasing temperature, frost events, cloud cover or rising CO2. The results from this thesis have important implications for future management of the Canadian boreal forest under progressive climate change.

Keywords: Canada
climate change
boreal forest
dendrochronology
Advisor: Thomas, Sean C.
Abiotic Conditions in Contrasting Environments: An Examination of Precambrian Shield Lotic Communities

The inherent complexity of the natural world has long been a central theme in ecological research, as the patterns and processes that govern ecosystems can operate at multiple spatial and temporal scales. It is clear that to develop general ecological frameworks, we must consider many different factors at different scales, and incorporate ideas from other disciplines. This thesis touches on several of these ideas, first through an analysis of literature, and then with field research examining the role of broad-scale abiotic factors on lotic systems. To determine how integrated aquatic science is currently understood among different researchers, I provide an analysis on communication and exchange of ideas among various subfields in aquatic science. I show that there are clear divisions within the aquatic science literature, suggesting that there is progress to be made on the integration of methods and ideas. Next, I examine the impact of a large-scale geological feature, the Canadian Precambrian Shield, on abiotic conditions in lotic systems, and how these conditions in turn influence the species assemblages of aquatic organisms. This is addressed with both historical survey data, as well as contemporary data, and as a whole, incorporates ideas concerning the relative influence of regional versus local factors, the importance of historical factors on species distributions, and the relationship between the abiotic environment and biological communities. These analyses show that there are distinct fish and macroinvertebrate communities in Shield lotic systems compared to those found in nearby off-Shield sites, indicating that the Shield is an important broad-scale factor influencing local biological communities. This finding, in conjunction with previous knowledge on the influence of historical factors, provides further insight on the structuring of lotic fish and macroinvertebrate communities in Ontario.

Keywords: community ecology
fish
macroinvertebrates
Precambrian Shield
Ontario
Advisor: Jackson, Donald Andrew
Race, Resistance and Co-optation in the Canadian Labour Movement: Effecting an Equity Agenda like Race Matters

The purpose of this research project was to analyze the dialectic of co-optation/domestication and resistance as manifested in the experience of racialized Canadian trade unionists. The seven research participants are racialized rank-and-file members, elected or appointed leaders, retired trade unionists, as well as staff of trade unions and other labour organizations. In spite of the struggle of racialized peoples for racial justice or firm anti-racism policies and programmes in their labour unions, there is a dearth of research on the racialized trade union members against racism, the actual condition under which they struggle, the particular ways that union institutional structures domesticate these struggles, and/or the countervailing actions by racialized members to realize anti-racist organizational goals. While the overt and vulgar forms of racism is no longer the dominant mode of expression in today’s labour movement, its systemic and institutional presence is just as debilitating for racial trade union members. This research has uncovered the manner in which the electoral process and machinery, elected and appointed political positions, staff jobs and formal constituency groups, and affirmative action or equity representational structures in labour unions and other labour organizations are used as sites of domestication or co-optation of some racialized trade unionists by the White-led labour bureaucratic structures and the forces in defense of whiteness. However, racialized trade union members also participate in struggles to resist racist domination. Among some of tools used to advance anti-racism are the creation of support networks, transgressive challenges to the entrenched leadership through elections, formation of constituency advocacy outside of the structure of the union and discrete forms of resistance. The participants in the research shared their stories of the way that race and gender condition the experiences of racialized women in the labour movement. The racialized interviewees were critical of the inadequacy of labour education programmes in dealing effectively with racism and offer solutions to make them relevant to the racial justice agenda. This study of race, resistance and co-optation in the labour movement has made contributions to the fields of critical race theory, labour and critical race feminism and labour studies.

Keywords: racism and organized labour
organizational resistance and cooptation
race and gender
labour education
Canadian labour movement
race, power and trade unions
white privilege and labour unions
racialized women and trade unions
Advisor: Quarter, Jack