VictorJuiz/thesis huggingface dataset:
Explaining Multiculturalism's Survival: Electoral Outcomes, Policy Design, and Veto Players

Multiculturalism, by which I mean the recognition and accommodation of cultural minorities borne out of individual and familial immigration, is a political project of the old political left, one that is logically inconsistent with the ideological positions of the political right. Due to this inconsistency, we should therefore expect multiculturalism to retreat following an ideological shift to the right in national level politics. However, this study shows that this does not always happen: sometimes multiculturalism survives an ideological shift to the right. This study argues that the likelihood of multiculturalism surviving an ideological shift to the right in national level politics is affected by electoral outcomes, by policy design and by the actions of critical veto players. More precisely, it argues that multiculturalism is more likely to survive an ideological shift to the right in national level politics when (1) parties of the political right secure enough votes in national level elections to govern but not to decide unilaterally (i.e. when they fail to form a minimum winning coalition), (2) failing that, when multiculturalism policies have been written into formal rules, have multiple stakeholders, or are ‘locked-in’ and therefore immune to the vagaries of electoral competition and (3) if multiculturalism policies are either de-institutionalized, have a single stakeholder, or are ‘open’ to re-examination, when critical veto players intercede to maintain the status quo despite strong partisan opposition to multiculturalism. Ironically, when the fate of multiculturalism rests in the hands of veto players their decisions to maintain the status quo seems to have little if anything to do with a genuine belief in the recognition and accommodation of cultural minorities. This study’s hypothesis of multiculturalism’s survival is developed through a step-by-step comparison of recent policy developments in three immigrant-receiving countries: Canada, Britain, and the United States. These countries share three things in common. Firstly, they were all part of a vanguard of immigrant receiving countries that turned towards multiculturalism during the latter half of the 20th century. Secondly, they have each recently experienced an ideological shift to the right in national level politics resulting from the electoral victories of center-right political parties. Thirdly, each of these cases demonstrates that multiculturalism has survived, albeit to varying degrees and in different ways, following an ideological shift to the right in national level politics. Due to these similarities, we can control for a stimulus that should have, all things being equal, entailed multiculturalism’s retreat across the three cases and, in so doing, identify the factors that provide the basis for a plausible explanation of multiculturalism’s survival.

Keywords: Comparative Politics
Electoral Outcomes
Multiculturalism
Policy Design
Public Policy
Veto Players
Advisor: Bertrand, Jacques
Tumour-suppressive and -promoting functions of Sufu in Sonic Hedgehog subgroup of medulloblastoma

Medulloblastoma (MB) is the most common malignant childhood brain tumor. Approximately 30% of MBs arise due to aberrant activity of the Sonic Hedgehog (SHH) signaling pathway. In SHH MBs, GLI proteins, particularly the major transcriptional activator GLI2, are highly expressed. In 60% of human SHH MBs, mutations in transmembrane signaling proteins PTCH1 and SMO are believed to unleash GLI activity. The exact roles of the intracellular GLI regulator SUFU in MB tumorigenesis remain poorly understood. SUFU mutations are identified in ~30% of infant SHH MBs which represent the most difficult-to-treat subgroup, because radiation and non-specific chemotherapy are both extremely harmful to infants and young children. Limited progress to date is due to the lack of faithful preclinical models and a poor molecular understanding of infant SHH MB. Strikingly, despite the Gli-inhibitory functions of Sufu, I found that loss of Sufu alone is insufficient to drive MB tumorigenesis in mice due to unsustained Gli activity. I showed that Sufu and Spop, an adaptor of E3 ubiquitin ligase, play central roles in suppressing MB tumorigenesis in mice through regulation of Gli2 protein stability. Using genetic mutants of Sufu and Spop, I established a novel preclinical mouse model of infant SHH MB with aggressive early-onset tumour formation. Through ChIP-Seq and RNA-Seq analyses, I identified more than 800 putative direct transcriptional targets of Gli2 in the Sufu;Spop infant MB mouse model, representing the first comprehensive dataset of Gli2 target genes. This study provides important insight to the molecular understanding of the transcriptional events underlying SHH MB tumorigenesis and reveals potential new therapeutic targets. I also found that loss of Sufu in Ptch1/Smo MB models leads to significantly prolonged survival, reduced Gli2 protein, and low overall pathway activity. Thus, Sufu acts positively to promote MB formation in Ptch1/Smo MB models, and represents a potential therapeutic target for MBs harboring PTCH1/SMO mutations.

Keywords: brain cancer
ChIP-Seq
Gli
hedgehog signaling
Medulloblastoma
Sufu
Advisor: Hui, Chi-chung
Microfluidic Platforms for Cell Encapsulation in Biomimetic Hydrogels

This thesis aims at studies of cell encapsulation and growth in hydrogel materials used as artificial extracellular matrices using microfluidic platforms. In the first project, I proposed and developed a method to overcome the challenge in the generation of microgels from highly viscous polymer solutions. I explored the application of the ‘‘direct injection’’ method for the preparation of microgels by adding a highly concentrated polymer solution or a gelling agent directly to the precursor droplets flowing through microchannels. I show that, the direct injection method can be used for microgel preparation from concentrated polymer solutions. The application of this method expands the range of polymers used for MF generation of microgels. In the second project, I describe the preparation of temperature-responsive nanofibrillar hydrogels from rod-shaped cellulose nanocrystals (CNCs) functionalized with a copolymer of N-isopropylacrylamide and N,N′-dimethylaminoethyl methacrylate. The composition of the copolymer was tuned to achieve gelation of the suspension of copolymer-functionalized CNCs at 37 °C in cell culture medium and gel dissociation upon cooling it to room temperature. The mechanical properties and the structure of the hydrogel were controlled by changing copolymer composition and the CNC-to-copolymer mass ratio. The thermoreversible gels were used for the encapsulation and culture of fibroblasts and T cells and showed low cytotoxicity. In the third project, I developed a microfluidic platform for the generation of two-dimensional (2D) arrays of micrometer-size cell-laden hydrogel modules (HMs) for cell encapsulation and culture. Fibroblast cells (NIH 3T3) and non-adherent T cells (EL4) encapsulated in HMs showed high viability and proliferation. The platform was used for real-time studies of the effect of spatial constraints and structural and mechanical properties of HMs on cell growth, both on the level of individual cells. In the fourth project, I developed a microfluidic platform to generate 2D arrays of multicellular cancer spheroids (MCSs) in hydrogels formed by chemically modified hyaluronic acid (HA). I analyzed the properties of MCSs encapsulated in HA hydrogels, discussed important factors to consider in their preparation and showed potential advantages of the MF platform for fundamental studies in cancer cell biology and drug screening. This work requires further optimization and development.

Keywords: 2D arrays
Extracellular matrix
Hydrogel
Microfluidics
Multicellular cancer spheroids
Nanofibrillar gel
Advisor: Kumacheva, Eugenia
Delineating Transforming Mechanisms of the C19MC OncomiR Cluster in Embryonal Brain Tumours

Central nervous system-primitive neuroectodermal tumours (CNS-PNET) represent a distinctly aggressive and clinically heterogeneous class of embryonal brain tumours with poorly understood biology. Previously, our lab discovered that a highly aggressive CNS-PNET subgroup (Group 1/C19MC-altered) is distinguished by C19MC amplification/TTYH1-C19MC gene fusions and high expression of the RNA binding protein, LIN28. Together with prior observations that C19MC alters human neural stem cell growth phenotypes, these findings suggest C19MC as a critical modulator of neural differentiation. However, the molecular mechanisms by which C19MC OncomiRs alter neural differentiation and mediate transformation are unclear. My thesis project investigated the hypothesis that the C19MC OncomiR cluster drives tumourigenesis by inhibiting critical neural differentiation pathways to promote multipotent cell states. My studies demonstrate that C19MC OncomiRs enhance cell cycle progression and neural proliferation through additive inhibitory effects on cell cycle checkpoint regulators p21, p27 and RBL2. Furthermore, my studies show C19MC upregulates the de novo DNA methyltransferase DNMT3B via inhibition of RBL2, leading to distinct methylation signatures. Most significantly, my studies discovered a novel hybrid super-enhancer resulting from TTYH1-C19MC fusion that powerfully drives a C19MC/LIN28 feedback circuit to regulate expression of DNMT3A and DNMT3B and promote a primitive-neural epigenetic state. Collectively, my results point to C19MC and LIN28 as major oncogenic drivers in Group 1/C19MC-altered embryonal brain tumours.

Keywords: Brain tumours
C19MC
Cell cycle
Epigenetics
LIN28
Neural differentiation
Advisor: Huang, Annie
The Production and Use of Administrative Documents in Somerset from Glanvill to Magna Carta

The Production and Use of Administrative Documents in Somerset from Glanvill to Magna Carta Robin Sutherland-Harris Doctor of Philosophy Centre for Medieval Studies University of Toronto 2016 Abstract This thesis studies how various kinds of administrative documents were produced and used through the late twelfth and early thirteenth centuries within the geographical and administrative territory bounded by the shire of Somerset and the diocese of Bath and Wells. Documents were increasingly part of administration in medieval England at all levels, from royal government to the local land market, from archbishops to cathedral canons. Parallel to the growing importance of administrative texts, an increasingly regularized body of administrative personnel also emerged during the twelfth and thirteenth centuries. This thesis is therefore situated in the intersection of a flourishing documentary culture and a burgeoning administrative class. Theoretical frameworks provided by scholarship on the partial shift from memory to the written word, on textual communities, and on pragmatic literacy inform the analysis throughout. Focussing on the production and use of administrative documents over a short time period and in a specific region makes it possible to approach them in detail and at multiple levels. At the level of the institution, both the diocese of Bath and Wells and the monastery of Glastonbury made use of administrative documents while in conflict with one another. At the level of the individual, the archdeacons of the diocese found a range of administrative roles in royal government, in which they relied on pragmatic literacies tailored to their individual circumstances. At the level of the documents themselves, connections between surviving charter originals reveal the articulation of large-scale changes in documentary and administrative culture in the uneven small-scale nuances of scribal and chancery production. Each chapter examines documentary culture and pragmatic literacy in the local context, exposing bureaucratic rather than literary or religious reading communities. Rather than the high-culture focus adopted by most studies of medieval literacy, the emphasis here is on the more wide-spread and practically engaged world of administrative bodies, personnel, and documents; this allows a â core sampleâ of evidence from a local temporal and geographical microcosm to be tested against our understanding of macrocosmic changes in the uses of texts and the roles of literacy in the medieval west.

Keywords: Administrative history
Charters and diplomatics
Medieval England
Advisor: Gervers, Michael
Genetic Analysis of Tumor Progression in the Mouse Mammary Gland

Genetic alterations that cooperate with TP53 mutation in breast cancer (BC) are largely unknown. Using a dominant-negative Trp53LSL-R270H/+ mouse strain, I found Trp53 alteration cooperates with Her2/Neu over-expression, but not with hemizygous deletion of Gata3, Runx1, or Nf1. To identify other genes cooperating with mutant Trp53, I completed a Sleeping Beauty (SB) mutagenesis screen in mice. This identified known cooperators such as Met, and other candidates such as Notch1. Cooperation between activated Notch1 and Trp53LSL-R270H/+ was validated in vivo. In addition to coding mutations, chromosomal copy number changes are also important in BC. To identify genes that contribute to mammary tumorigenesis upon copy number alteration, I compared genes targeted by transposons in SB mice carrying Trp53LSL-R270H/+, R26LSL-Pik3ca(Mut)/+, R26LSL-Stat3C/+, or no mutant allele. This enabled me to identify genes altered in all cohorts (e.g. Rasa1), in several but not all backgrounds (e.g. Met), and those that only occurred in the presence of a single driver (e.g. Mll3, Exoc4, and Cul1 loss in Pik3ca-mutant tumors). Importantly, many genes targeted by SB transposons map to loci syntenic with regions commonly gained/lost in human BC. Thus, they likely represent haploinsufficient tumor suppressors or oncogenes. Guided by SB results, the oncogenic interaction between R26LSL-Pik3ca(Mut)/+ and loss/activation of Notch1 was validated in vivo. Additionally, I distinguished genes altered in metastatic lesions from SB mice. This revealed genes previously implicated in BC dissemination (e.g. Hipk2) and novel abnormalities (e.g. loss of Fbxl17). Lastly, to assess the oncogenic potential of ELF3 (which maps to human chromosome 1q and is frequently gained/amplified in human BC), I generated a Cre-conditional Rosa26-targeted Elf3 transgenic strain (R26LSL-Elf3). Using SB mutagenesis, I showed genes such as Cul5 and FoxP1 were disrupted in Elf3 over-expressing SB mammary tumors, while metastases from these mice selected for a distinct set of insertions (e.g. Pard3 disruption).

Keywords: Breast Cancer
Mouse Models
p53
PI3K
Sleeping Beauty Mutagenesis
Stat3
Advisor: Egan, Sean E
The Application of Section 8 of the Canadian Charter of Rights and Freedoms to Searches Conducted for Purposes of National Security Intelligence

This paper proposes an approach to the interpretation and application of section 8 of the Canadian Charter of Rights and Freedoms where searches by the state are effected in the course of ensuring national security, more specifically in producing national security intelligence. Having outlined the principles developed by the courts in applying section 8, it suggests that the stateâ s interest in national security is one of the highest order, resulting in it weighing heavily in balancing against individualsâ privacy interests. In the course of its examination, it describes national security intelligence and criminal investigations as different paradigms, justifying different treatments. It proposes that the Hunter v Southam standard remains available in areas where privacy stakes are the most serious, to begin to slide toward that of reasonable suspicion at earlier points than it would in criminal matters, remaining modulated by the expectation of privacy or degree of intrusion.

Advisor: Roach, Kent
Surface Adsorption Studies of CO2 and H2 on Defected Indium Oxide: Insights into Gas-Phase Heterogeneous Photocatalysis

The conversion of CO2 into fuels or chemical feedstocks is valuable for not only mitigating the rising atmospheric concentration of CO2, but also for utilizing CO2 as a globally available, abundant, and renewable resource. Indium oxide defected with oxygen vacancies and hydroxides, In2O3-x(OH)y, is a catalyst material that facilitates the light-assisted, gas-phase heterogeneous reduction of CO2 via the reverse water gas shift (RWGS) reaction, CO2 + H2 -> CO + H2O. The extent of defects in In2O3-x(OH)y correlates strongly with the rate of CO2 conversion as well as the CO2 adsorption capacity. Prior to this work, the specific interactions between the RWGS reactants, CO2 and H2, and the In2O3-x(OH)y surface were largely unknown. The work herein explores the In2O3-x(OH)y surface chemistry through carefully designed in situ thermogravimetric analysis and infrared spectroscopy techniques to identify and investigate surface-adsorbed CO2 and H2 species. CO2 adsorbs as a complex mixture of carbonates, bicarbonates, carboxylates, and linear CO2 species, which adsorb at readily available and specific surface sites, forming a partial monolayer with varying adsorption strengths. H2 easily reduces the In2O3-x(OH)y surface, resulting in a broad and intense infrared absorbance peak due to the delocalization of conduction band electrons, the intensity of which decreases with an increase in defects, agreeing with our understanding that defects promote charge trapping at the surface to be used in chemical reactions. The coadsorption of CO2 and H2 results in a strongly adsorbed formate species, providing indirect evidence for H2 heterolytic dissociation, in addition to possibly identifying formate as an intermediate for the RWGS reaction or a bystander that instead leads to methanol synthesis. Through detailed CO2 and H2 adsorption studies, this thesis has provided us with valuable insight into the In2O3-x(OH)y surface and its complex chemistry â a critical contribution to the development of a viable CO2 utilization technology.

Keywords: Adsorption
Carbon dioxide
Catalysis
Nanochemistry
Photocatalysis
Surface science
Advisor: Ozin, Geoffrey A
The Relations of the Crimean Khanate with the Ukrainian Cossacks, the Polish-Lithuanian Commonwealth and Muscovy during the Reign of Khan Islam Giray III (1644-1654)

This dissertation analyzes the relations of the Crimean Khanate with the Ukrainian Cossacks, the Polish-Lithuanian Commonwealth and Muscovy during the reign of Khan Islam Giray III (1644 - 1654). Islam Giray’s reign coincided with some of the most turbulent years of the Crimean Khanate’s history. Shortly after his accession to the throne in summer 1644, a quarrel between his nobles and palace guards during the return from a Circassian campaign turned into an exhausting civil war between him and his nobility. The Khanate’s relations with its northern neighbours were also deteriorating as Warsaw and Moscow decided to take action against the attacks of the Tatars and stopped tribute/gifts payments to Crimea. Under these circumstances, the Cossack rebellion of 1648 against the Commonwealth under the leadership of Bohdan Xmel’nyc’kyj was a golden opportunity for Islam Giray to reassert his position as ruler in Crimea and strengthen the Khanate’s position in eastern European affairs. While the khan gave military support to the Ukrainian Cossacks throughout their war with the Commonwealth, he was never willing to allow the collapse of Warsaw’s authority over Ukraine. Instead he aimed to be a mediator between the Cossacks and the Commonwealth forcing them to agree to peace treaties that would reconcile their contending demands. Islam Giray also intended to ally with Warsaw and Xmel’nyc’kyj for the conquest and partition of Muscovy, acquiring the Volga patrimony of the Golden Horde, Kazan and Astrakhan, for the Khanate. However, as the Cossacks and the Commonwealth were overwhelmed by their mutual problems, they were uninterested in participating in an anti-Muscovite alliance. Eventually, a decisive blow to Islam Giray’s mediatory position and his anti-Muscovite schemes came as the Ukrainian Cossacks could not reach a settlement with Warsaw and decided to submit to Muscovy in 1654. Now, towards the end of his reign, the khan found himself at a crossroads between maintaining his alliance with the Ukrainian Cossacks and taking sides with the Commonwealth against the Ukrainian-Muscovite rapprochement.

Keywords: Bohdan Xmel'nyc'kyj
Islam Giray III
Muscovy
Poland-Lithuania
The Crimean Khanate
Ukraine
Advisor: Ostapchuk, Victor
Dynamics of Speciation in Neotropical Birds: Diversification Rates, Introgression and Reproductive Isolation

Tropical rainforests â covering 7% of the earth's surface â are areas of exceptionally high biodiversity compared to other ecosystems. However, no consensus has been reached as to the primal cause of high tropical diversity. In this thesis, I used a combination of phylogenetic and population genetic methods to address whether speciation is an important driver of diversification patterns and to determine the genetic architecture of reproductive isolation and the frequency of introgression during the diversification process in the species-rich Neotropics. I developed and fit a character-state dependent diversification model to a global avian phylogeny and found consistent support across replicate clades for extinction as a key driver of species richness gradients. In contrast, an association between speciation or dispersal rates with species richness was not consistently found. To better understand the process of speciation in the tropics, I studied reproductive isolation in two genera of suboscine birds. My results showed that pre-zygotic reproductive barriers play a less important role in the tropical speciation process than at high latitudes, with reproductive isolation driven largely by post-zygotic genetic incompatibilities. I also found evidence of frequent introgression events during the diversification process in the Neotropical genus Dendrocincla. My analyses showed different instances of historical introgression events among closely and distantly related lineages of Dendrocincla, demonstrating that introgression may often be a common phenomenon during the diversification process in the Neotropics. These results contribute to our understanding of the evolutionary processes that drive diversification and how speciation evolves in areas of high species richness.

Keywords: Birds
Extinction
Hybridization
Neotropics
Reproductive Isolation
Speciation
Advisor: Weir, Jason T
The "Whys" of Charity Regulation

Why do we regulate charities? What is it about charities that requires them to be regulated because they are charities? What should charity regulation aim to achieve and why? These are the questions this thesis sets out to address. I begin by emphasizing the need for critical analysis of the underlying purposes, or “whys”, of charity regulation. I then go on to identify two such purposes: encouraging the pursuit of charitable purposes; and holding those who pursue charitable purposes to account. The thesis outlines how these regulatory “whys” result from and can, thus, be justified by the particular problems charities face thanks to their legal definition, which I argue is the only possible basis for illuminating the purposes of charity sector specific regulation. I conclude by commenting on the further research needed to develop a more complete theory of charity regulation capable of informing institutional design.

Keywords: Charity Law
Regulation
Advisor: Satterthwaite, Emily