VictorJuiz/thesis huggingface dataset:
Grain, Stone, and Red Velvet: The Material Assemblages of a City on the Vistula River in Poland, c. 1555 - c. 1655
Keywords: Building
Commodity
Granary
Materiality
Space
Urban

This dissertation examines Kazimierz Dolny, a city situated at the geo-political center of the vast Polish-Lithuanian Commonwealth within a time span of approximately one hundred years, 1550-1655. During this time the city became a significant mercantile port due to its location on the Vistula River - the main trade route in early modern Poland. The merchants of Kazimierz Dolny oversaw the storage of grain and its export to Gdansk, a commodity that was then shipped to other Baltic and North Sea ports. From this exchange, the merchants made significant financial gains that were channeled into the renovation of their city. Their investments included private stone-constructed granaries and ornamented residences, as well as public commissions such as churches and chapels. This thesis considers the ways in which mercantile networks and the movement of goods shaped a distinct material world where architecture functioned as a commodity.
A Biologically Inspired Hierarchical Cyber-Physical Integrated Security Analysis Framework for Smart Grids
Keywords: Cyber-Physical Integrated Security
Flocking-Based Dynamical Systems
Smart Grid

The last few years have witnessed the radical transformation in structure and functionality of electrical energy systems. Such systems were traditionally executed in the physical world and are now also cyber-enabled. This cyber-enabled energy system, called smart grid, can be envisioned as the marriage of information technology with the electricity network. While its increased dependence on cyber infrastructure aims to enable greater reliability, efficiency and capacity of power delivery, this reliance also creates a host of unfamiliar vulnerabilities. Due to the highly integrated and connected nature of smart grids, it is important to account for their salient cyber-physical coupling when making critical design decisions and identifying solutions to promote security. In this dissertation, we present a biologically-inspired cyber-physical integrated security analysis framework for maintaining smart grid stability under various forms of physical and cyber attacks. Through this security analysis framework, we demonstrate real-time cyber-physical integrated control and communication strategies using "wisely"-placed Phasor Measurement Units (PMUs) and energy storages. Our research has evolved in three stages. We first propose a cyber-physical multi-agent dynamical systems paradigm to model the cyber-physical interactions in smart grids, in which each agent is modeled as having dynamics that synergistically describe physical and information couplings with neighboring agents. Inspired by the analogy between the flocking rules and the smart grid stability requirements, we develop a flocking-based scheme to formulate the cyber-physical integrated action for each agent. In the second stage, we extend the multi-agent dynamical systems paradigm to a two-tier hierarchical framework which reduces information acquisition by leveraging physical couplings between the agents and applying cyber controls selectively on critical agents. In the context of the hierarchical framework, we propose a witness-based security protocol for identifying and mitigating information corruption on the critical agents. In the third stage, we develop an intelligent multicast routing strategy for timely synchronous data delivery in smart grids, called Goal-Seeking Obstacle and Collision Evasion (GOALiE), which is resilient to network congestion and Denial-of-Service (DoS) attacks.
The Imprinted Polycomb Group Gene Sfmbt2 is Required for Trophoblast Maintenance and Placenta Development
Keywords: Extraembryonic Tissue
Imprinting
Placenta
Polycomb Group Protein
SFMBT2
Trophoblast Stem Cells

Embryos with two maternal copies of the genome and no paternal contribution (parthenogenetic embryos), die early in development due to failure to sustain a functional extraembryonic tissue of trophoblast origin. The reported phenotypes of parthenogenetic embryos have been correlated with absence of expression from an imprinted paternally expressed gene (PEG) with critical roles in maintenance of trophoblast stem (TS) cells and their derivatives. To find the genes responsible for the observed phenotypes of the murine parthenogenetic embryos, I performed a survey of known PEGs and identified the paternally expressed
Young, Queer and Trans, Homeless, and Besieged: A Critical Action Research Study of How Policy and Culture Create Oppressive Conditions for LGBTQ Youth in Toronto's Shelter System
Keywords: homelessness
homophobia
LGBTQ
shelter services
transphobia
youth

This dissertation is about lesbian, gay, bisexual, transgender, transsexual, and queer (LGBTQ) youth and the shelter system. This work focuses on the denial of home and safety to queer and trans youth. Over approximately two years, different groups of people came together to discuss what is holding up and sustaining the homophobia and transphobia in the shelter system, how homophobia and transphobia occurs and is managed in the shelter system, and how broader policy issues serve to create oppressive contexts for LGBTQ youth. This is a Critical Action Research study that was informed by Critical Ethnography and Institutional Ethnography. In order to investigate what disjunctures occur for LGBTQ youth in the shelter system and how those disjunctures come about, this dissertation draws upon one-on-one interviews with LGBTQ youth experiencing homelessness, shelter Executive Directors, City of Toronto management, and training facilitators; focus groups with frontline shelter staff; and training observations. This study suggests that it is both the excessive bureaucratic regulation and the lack of necessary bureaucratic regulation in highly significant areas, that play a key role in creating the disjunctures that occur for queer and trans youth in the shelter system. This dissertation describes the findings of this study in five major themes, which include: Homophobia and Transphobia in the Shelter System, LGBTQ Youth Invisibility, Inadequate, Invasive and Otherwise Problematic Rules, Lack of Knowledge, and Inconsistent Conformity to Formal Rules. A Digital Storytelling project was created with one youth and was used as a Knowledge Mobilization strategy for this study. The film helped generate extensive media attention and facilitated change in the shelter system, at the City of Toronto, and at a policy level. This research study has made it possible for the voices of LGBTQ homeless youth to be heard in the context of a critical public health and social justice problem. Detailed policy and practice recommendations and changes to the Toronto Shelter Standards are provided at the end of this dissertation and are meant to help Toronto's shelter system become safe, accessible, and supportive of LGBTQ youth.
PXR-mediated Regulation of Placental Drug Transporters Impact on Fetal Exposure to Lopinavir
Keywords: ABC Transporters
Lopinavir
Placenta
PXR

Globally, there are close to 20 million women living with HIV. An increasing number of these women are of child bearing age. Current guidelines recommend treatment of all pregnant women with highly active antiretroviral agents to both maintain maternal health and to prevent the vertical transmission of the virus. Maintaining a balance between adequate levels of antiretroviral in the fetal system and preventing fetal toxicity are key to the success of this strategy. Despite increasing use, little is known about the transplacental accumulation of these agents. ABC drug transporters at the placental surface are believed to play an important role in the protective function of the placenta. This thesis explored the involvement of Pregnane X Receptor (PXR), an established regulator of drug transporters in the liver and intestine, in the regulation of placental drug transporters and the impact of PXR genotype and associated differences in placental transporter levels on fetal drug accumulation of lopinavir, a key antiretroviral used extensively in pregnant women. We examined the role of the nuclear receptor at the placental interface in PXR knockout and wildtype mice. Pegnenolone-16-á-carbonitrile (PCN) treatment failed to induce PXR and target genes in the placenta in contrast to the liver. Furthermore, an inverse relationship between placental PXR expression and the expression of Pgp, Mrp 1-3 and Bcrp was observed in the placental tissue. PXR heterozygotes were bred in order to generate pregnant dams with varying expression of placental transporters in individual fetal units within the same dam. This model was used to study the impact of fetal genotype and placental transporter expression on fetal exposure to lopinavir within the same dam. A two fold higher fetal accumulation of lopinavir was observed the PXR null placentas as compared to the wild types. An inverse relationship was observed between the placental expression of Mdr1a and fetal exposure to lopinavir (p
Development and Pluralization of the Media of Security Sensitive Ethnic Minority Groups: the Experience of South Eastern European States
Keywords: ethnic minorities
ethnic minority media
ethnic parties
ethnic party systems
media
media pluralism

This thesis is about the media of security sensitive ethnic minority groups in South Eastern Europe. Why some of them enjoy developed media spheres whereas others are media-deprived? Why operating in similarly structured liberal contexts, the media spheres of some minorities develop as pluralist and liberal, whereas those of others as non-pluralist and authoritarian? In search for answers to these questions, this dissertation compares the media of Turks in Bulgaria, Albanians in Macedonia and Hungarians in Romania. It proposes a model of development of pluralist media spheres of security sensitive ethnic minorities, incorporating variables from three levels of analysis (group, state and system), namely, political cohesion of ethnic minority groups, their level of education, status of interethnic relations, media funding mechanisms, external system pressure and grand polity design.
Free Radical Determinants of Teratogenesis: Oxidative Damage and Biochemical Signalling by Reactive Oxygen Species
Keywords: Bisphenol A
DNA damage
Ethanol
Methamphetamine
Oxidative Stress
ROS signalling

Prenatal exposure to xenobiotics can lead to the production of reactive oxygen species (ROS) that alter signal transduction or oxidatively damage cellular macromolecules such as DNA and protein. During development, ROS play an important role in physiological signalling, suggesting that tight regulation of oxidative stress is imperative for normal development. My research employed two models: one to examine the role of ROS-mediated signalling in teratogenesis and the other to examine the role of oxidative DNA damage and repair. Using the industrial plasticizer and environmental contaminant, bisphenol A (BPA), I found that a single high dose exposure during early fetal development can increase ROS production, causing protein and DNA oxidation in fetal brain, accompanied by postnatal increases in hyperactivity and loss of fear conditioning and olfactory discrimination. BPA-exposed mice have increased neocortical cell proliferation that may involve activation of the PI3K/Akt/mTOR pathway based on the observed increase in oxidation of phosphatase and tensin homolog (PTEN). To elucidate the importance of DNA damage during embryonic development, I generated a conditional knockout mouse line for the breast cancer susceptibility gene (Brca) 1. While individuals with decreased BRCA1 develop normally, they have a greater risk of developing breast and ovarian cancers, and Brca1 null mice are not viable, suggesting that the gene is essential for normal development. Using the pro-oxidative drugs ethanol (EtOH) and methamphetamine, we have shown that heterozygous BRCA1-deficient mice develop normally but are more susceptible to ROS-initiated embryopathies in embryo culture. Furthermore, BRCA1-deficient females show greater susceptibility to ROS-initiated neurodevelopmental deficits than their BRCA1-normal littermates. ROS adversely affect embryonic and fetal brain development via both altered biochemical signalling and oxidative damage, the latter of which is modulated by conceptal DNA repair. Further identification of the complex interactions involved in the dynamic balance among ROS production and detoxification, and downstream repair of macromolecular damage, may provide insight into personal risk for developmental deficits.
Athens in Rome, Rome in Germany: Nicodemus Frischlin's 1586 Translations of Aristophanes
Keywords: Aristophanes
Comedy
Nicodemus Frischlin
Renaissance
Rudolf II
Translation

This thesis presents a critical analysis of Nicodemus Frischlin's 1586 Latin translations of Aristophanes' Plutus, Clouds, Acharnians, Frogs, and Knights. This analysis uses criticism from the fields of translation studies to get to the heart of the cultural milieu for which Frischlin produced these translations. One major question this thesis will seek to answer is why, exactly, a German humanist would think it a good idea to translate and popularize the works of an author typically thought to be too obscene and topical to be of any value to the Christian readers of the European Renaissance. This thesis answers this question by undertaking the necessary analyses of the rapidly shifting political, religious, and educational boundaries in Frischlin's Holy Roman Empire at the close of the 16th century. Within this fragmented state, Frischlin's work reached many different groups and effected them in different ways, and so this thesis also attempts to trace these varied reactions through the different political and cultural contexts in which Frischlin worked at different stages, exposing the literary and poetic expectations of the multiple audiences who read and happily re-published his work. Chapter one introduces the subject, with basic background information on the general consensus concerning Aristophanes at the time Frischlin began his work. Chapter two handles the question of translation directly, establishing the methods Frischlin employed in producing his translations, and the means by which we can best criticize and understand them. Chapter three examines Frischlin's relationship to the educational curricula of his day, and the purpose his translations served within those evolving curricula. Chapter four analyzes the relationship of Frischlin and his translation to the governmental structures within which he had to work and seek patronage. Chapter five seeks to establish what lasting impact Frischlin's approach to Aristophanes had on later generations of scholars and artists. Chapter six concludes the dissertation by summarizing the preceding arguments and suggesting directions that similar research can and should take in the future.
Functional Characterization of UVRAG and ANP32B in Immune Cells Using Gene-deficient Mice
Keywords: Autophagy
EAE
Endocytic Trafficking
Knockout mice
LCMV infections
T cell homeostasis

This dissertation is a functional characterization of UVRAG and ANP32B in the immune system using gene deficient mice. Focus 1: UVRAG is a putative tumour suppressor with potential roles in autophagy and endocytic trafficking. Despite a plethora of in vitro data, the in vivo role of this gene remains poorly understood. Here, we report the generation and characterization of the T cell specific UVRAG deficient mice. These mice exhibited normal T cell development but impaired homeostasis in the periphery, rendering them unable to clear LCMV infections. We demonstrate that UVRAG may be dispensable for T cell autophagy but it is required for the homeostatic survival and proliferation of naïve T cells. Taken together, our data provide insights into the control of autophagy in T cells and identify UVRAG as a new regulator of naïve T cell homeostasis. Focus 2: ANP32B belongs to a highly conserved and broadly expressed family of ANP32 proteins that have been implicated in many cellular functions. Based on previous analyses of mice bearing targeted mutations of Anp32a or Anp32e, there has been speculation that all ANP32 proteins play redundant roles and are dispensable for normal development. Here, we report that ANP32B expression is associated with poor prognosis in human breast cancer. Using ANP32B-deficient mice, we demonstrate a hierarchy of importance for the mammalian Anp32 genes, with Anp32b being the most critical for normal development. In addition, we reveal important roles for ANP32B in differentiation, homeostasis and activation of immune cells. Together, these are novel findings implicating ANP32B in mammalian development and immune cell function.
Na+ Transport and Toxicity in Plants
Keywords: Compartmental analysis
Ion transport
Radiotracers
Salinity
Sodium
Toxicology

Soil salinity is an urgent and global agricultural problem, affecting more than 80 million hectares of arable land. While sodium can be benign and even beneficial to plants at low concentrations, severe toxicity symptoms are found in many species at high, saline, concentrations. Toxicity is initiated by the entry of Na
Phosphotyrosine Signalling and Regulation of the Fibroblast Growth Factor Receptor 3 in Multiple Myeloma
Keywords: kinase
mass spectrometry
phosphatase
phosphorylation
protein
tyrosine

Protein phosphorylation on tyrosine residues is a critical post-translational modification involved in most cellular processes. Reversible tyrosine phosphorylation events are controlled by the opposing action of protein tyrosine kinases and protein tyrosine phosphatases. Activation of transmembrane receptor tyrosine kinases by ligand binding initiates tyrosine phosphorylation cascades, thus allowing the transmission of signals from the extracellular space to intracellular effectors. The FGFR3 is one such receptor tyrosine kinase involved in numerous biological processes and its dysregulated activity is involved in developmental skeletal disorders as well as malignancies such as the bone marrow cancer multiple myeloma. The lack of comprehensive understanding of FGFR3 signalling as well as its involvement in multiple myeloma, a refractory and deadly disease, led me to investigate its signalling network in myeloma cells by mass spectrometry. Following label-free quantification of phospho-peptides co-modulated with inhibition or activation of FGFR3, I propose an outline of the FGFR3 network, thus considerably increasing our knowledge of the components involved in FGFR3 signalling in myeloma as well as the tyrosine residues phosphorylated within this network. Additionally, this initial screen identified several activated tyrosine kinases, including FGFR3, which contained the D/EYYR/K motif within the activation loop of their kinase domain. This sequence has been proposed as a recognition motif for the protein tyrosine phosphatases PTPN1 and PTPN2. Lentiviral-based, shRNA-mediated knockdown of either of these phosphatases resulted in increased tyrosine phosphorylation of the FGFR3 activation loop. However, each of these phosphatases displays preferential targeting of different FGFR3 populations, depending on the glycosylation state and therefore localization of the receptor. Moreover, loss of these phosphatases differentially affects FGFR3 protein levels in various myeloma cell lines. Taken together, these results provide new knowledge about the signalling network of FGFR3 in multiple myeloma as well as revealing aspects of the mechanisms involved in its regulation by PTPN1 and PTPN2.
Anti-vascular Endothelial Growth Factor Therapy in Mouse Models of Vascular Dysplasia and Chronic Colitis
Keywords: Angiogenesis
Anti-VEGF therapy
HHT
IBD
VEGF

Hereditary hemorrhagic telangiectasia (HHT) and inflammatory bowel disease (IBD) are associated with pathological angiogenesis. Vascular endothelial growth factor, VEGF, is a major angiogenic modulator implicated in HHT and IBD. Hence, we hypothesized that VEGF-targeted therapy might be beneficial in these disorders. HHT is an inherited vascular dysplasia characterized by arteriovenous malformations in organs leading to severe complications. HHT is caused by mutations in Endoglin (ENG; HHT1) or Activin receptor-like kinase 1 (ALK1; HHT2) genes, coding for transforming growth factor (TGF-) superfamily receptors. We studied the angiogenic phenotype of Endoglin and Alk1 heterozygous mice and determined their response to anti-VEGF therapy. We demonstrated that lungs, but not liver, heart or colon, showed dysregulated angiogenesis, characterized by reduction in peripheral microvessel density (MVD). An increase in angiostatic thrombospondin-1 (TSP-1) and vascular destabilizing factor angiopoietin-2 (Ang-2), was associated with reduced MVD in Eng+/- and Alk1+/- lungs respectively. Surprisingly, anti-VEGF treatment increased peripheral pulmonary MVD and normalized levels of TSP-1 and Ang-2, suggesting that the treatment restored the angiogenic balance by distinct pathways in HHT1 and HHT2 models. IBD is characterized by severe, relapsing gut inflammation, leading to multiple complications. Pathological angiogenesis in chronic colitis is persistent, excessive and abnormal. We tested the effect of anti-VEGF therapy in chronic colitis using the Eng+/- mouse model subjected to dextran-sodium sulphate, characterized by severe, chronic intestinal inflammation and pathological angiogenesis. We demonstrated that pathologic angiogenesis is characterized by high colonic MVD and increased in vivo microvascular hemodynamics, as assessed by ultrasound. Interestingly, colitic Eng+/- mice showed an inflammation-induced rise in colonic endoglin, several pro-inflammatory cytokines and myeloid chemotactic factors. They had a further increase in G-CSF and amphiregulin, when compared to wild type mice. This suggests that endoglin might have a triple role, as a protective regenerative factor and as a marker of inflammation and angiogenesis in colitis. Importantly, anti-VEGF therapy showed effects associated with resolution of in vivo and in vitro inflammation and pathological angiogenesis in the Eng+/- model of chronic colitis. Our findings establish the foundation for future translational studies in patients with vascular dysplastic and chronic inflammatory diseases.
Genetic Analysis of Retinopathy in Type 1 Diabetes
Keywords: diabetes complications
Diabetes Mellitus
Type 1
diabetic retinopathy
Genome-Wide Association Study
GWAS
Polymorphism
Single Nucleotide

Diabetic retinopathy (DR) is a leading cause of blindness worldwide. Several lines of evidence suggest a genetic contribution to the risk of DR; however, no genetic variant has shown convincing association with DR in genome-wide association studies (GWAS). To identify common polymorphisms associated with DR, meta-GWAS were performed in three type 1 diabetes cohorts of White subjects: Diabetes Complications and Control Trial (DCCT, n=1304), Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR, n=603) and Renin-Angiotensin System Study (RASS, n=239). Severe (SDR) and mild (MDR) retinopathy outcomes were defined based on repeated fundus photographs in each study graded for retinopathy severity on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Multivariable models accounted for glycemia (measured by A1C), diabetes duration and other relevant covariates in the association analyses of additive genotypes with SDR and MDR. Fixed-effects meta-analysis was used to combine the results of GWAS performed separately in WESDR, RASS and subgroups of DCCT, defined by cohort and treatment group. Top association signals were prioritized for replication, based on previous supporting knowledge from the literature, followed by replication in three independent white T1D studies: Genesis-GeneDiab (n=502), Steno (n=936) and FinnDiane (n=2194). No SNP reached genome-wide significance in survival meta-GWAS for SDR. In a case-control meta-GWAS, however, SNPs in