VictorJuiz/thesis huggingface dataset:
Genomic Profiling of Familial Early-age of Onset Breast Cancer

Familial breast cancers make up a small proportion of all breast cancer cases. Mutations in known breast cancer susceptibility genes, such as BRCA1 and BRCA2, can explain a third of familial breast cancer risk. A woman's breast cancer risk increases two-folds if she has an affected first degree relative and the risk increases if the relative was diagnosed at a young age. Thus, it is important to understand the genetic architecture and the genes involved in breast cancer pathogenesis in individuals diagnosed at a young age with a family history of breast cancer. In this thesis I took advantage of archival and frozen specimens ascertained from the Familial Breast Cancer Registry and the Toronto Axillary Node Negative (ANN) Breast Cancer Study to investigate the copy number changes in fourteen non-BRCA1/2-mutated breast cancer cases with a family history and young age of onset to examine copy number analysis using genomic microarrays. The most recurrent alterations included losses of 8p and 17p, single copy gains of 1q and 8q, and high level amplification of ERBB2 and ZNF703. My work indicates there are some genomic regions that are more frequently aberrant in copy number among young familial breast cancer cases compared to independent datasets of young age of diagnosis cases. Next-generation sequencing was also used to study the exomes of 3 tumor-normal pairs and 20 unmatched ANN tumors. Genomic analysis of the tumor-normal pairs found one case with heterozygous variants in both the germline and tumor genome in three breast cancer susceptibility genes, BRCA1, BRCA2, and RAD50. It was observed that ten of the unmatched tumors contained significantly fewer variants than the other ten unmatched samples. The cases with fewer variants had between 866-3,459 variants and the cases with a high number of variants contained 6,452-77,870 variants. The samples with more variants also had significantly more C:G>A:T transversions, evidence for defective mismatch repair that warrants investigation in future studies.

Keywords: breast cancer
cancer
copy number
exome-sequencing
microarray
Advisor: Andrulis, Irene L
Cartographers as Critics: Staking Claims in the Mapping of American Literature

“Cartographers as Critics: Staking Claims in the Mapping of American Literature” recuperates the print culture phenomenon of literary map production, which became popular in North America around 1898. A literary map can be defined as any pictorial map that depicts imaginative worlds or authorial associations across geopolitical space. While notable examples have circulated for centuries in bound books, such as Thomas More’s _Utopia_ and William Faulkner’s _Absalom, Absalom!_, the majority of twentieth-century literary maps were ephemeral productions that have not survived in great numbers. These discursive documents functioned as compelling expressions of literary taste and cultural values; they circulated in magazines and newspapers, as gas station promotional giveaways and diner placemats, and as classroom “equipment.” Extant literary maps offer new perspectives on turn-of-the-twentieth century U.S. literary nationalism and the Public Library Movement, “fiction debates” and “Great Books” curriculums, the mid-century schism between anthropological folklorists and literary folklorists, and the role of popular cartography in U.S. print culture. Though today’s critics are generally unaware of the literary maps discussed here, these documents are consequential artifacts that have consistently equated canonized writers with pioneers and conquerors; in doing so, they have formulated literature as an extractable, finite, and controllable resource found on North America’s “literary frontiers.” Importantly, discursive literary maps make claims that are both critical assessments and assertions of territorial title. In doing so, they impose a cartographic framework on Native space that simultaneously evacuates and denies both the presence and possibility of Indigenous literatures. “Cartographers as Critics” seeks to problematize this ideological equation and to explore its critical implications for the recent “spatial turn” in the humanities and social sciences, as well as the burgeoning revitalization of literary map production and circulation now present on the Internet.

Keywords: Literary Map
Spatial Turn
Advisor: Justice, Daniel Heath
The Defence Research Board of Canada, 1947 to 1977

The Defence Research Board of Canada existed from 1947 to 1977. It was created because of the successful contribution of scientific management and specific military technologies to victory in the Second World War, and it was dismantled during a period of review and renewal of the government’s science and defence policies. The demise of the Defence Research Board demonstrated the triumph of business and public administration models over scientific management in spite of the successful defence research program. Among the successful projects of the Defence Research Board were satellites, research rockets, hydrofoils, nylon pile clothing, the wind chill factor, the strategic distinction between first and second nuclear strikes, open heart surgery, and blast trials. The strengths of the Defence Research Board were the scientific management practices that united the four Chairmen (Omond Solandt, Hartley Zimmerman, Robert Uffen and Léon L’Heureux) and the bench scientists. Over the course of its existence the Defence Research Board was shaped by six chains of events. 1. Solandt’s ability to recruit veterans from 1947 to 1953, 2. The election of John Diefenbaker and the ensuing conflict between Diefenbaker and civil servants, particularly over nuclear weapons, which led to the Royal Commission on Government Organisation and a decade of review of national defence policy (including two White Papers, integration and unification, and the Management Review Group), 3. The science policy review that followed from C.D. Howe retiring from politics and the reports of the Royal Commission on Government Organization, 4. The Defence Research Board’s brushes with francophone nationalism and separatism, 5. The criticisms leveled against the Defence Research Board by the Voice of Women, and 6. The changing of Canadian demographics and values in general. This thesis documents the story of the Defence Research Board against its international, national, scientific and historical contexts.

Keywords: Science and Technology
Research and Development
Military
National Defence
Cold War
Policy
Civil Service
Administration
Management
Advisor: Langins, Janis
Printed in Perfect Harmony: Publishers of Poetry in France, 1851-1900

In the second half of the nineteenth century in France, there emerged a series of publishers who were intimately tied to the genre of poetry as well as to specific avant-garde literary movements. Auguste Poulet-Malassis, the publisher of Charles Baudelaire; Alphonse Lemerre, the patron of the Parnassian poets; and Léon Vanier, who shepherded the works of the Decadents and Symbolists into the book market, serve as three examples. Before analyzing their careers and their catalogues in detail, the first two chapters of this interdisciplinary thesis, drawing on the methodologies of book history, literary history, the sociology of literature and bibliography, present both an overview of the history of publishing poetry in France, as well as a quantitative analysis of all poetry books listed in the Bibliographie de la France between 1851 and 1900. Through this general survey of the period as well as the three focused case studies, it is proposed that publishers of poetry deployed specific strategies, including fine luxury edition practices, that highlighted their printed products in an era of mass production and which were in harmony with the aesthetic ideals of the poets whose works they printed. However, due to the tensions between the demands of art and those of the market place, their relations with poets, and their own place in the field of literary publishing, remained fraught with discord.

Keywords: book history
poetry
publishing history
publishers
France
nineteenth century
Advisor: Portebois, Yannick
Human and Machine in Formation: An Ethnographic Study of Communication and Humanness in a Wearable Technology Laboratory in Japan

This dissertation reports on an ethnographic study of human-centered technology researchers, conducted in Japan between 2010 and 2012. Researchers in this field—a multidisciplinary group mostly of computer engineers, as well as complex systems scientists, biologists, and psychologists—claim that existing “machine-centered” technologies require users to behave like machines, resulting in burdensome and brittle social relations. In contrast, they attempt to create “human-centered technologies” that humans can interact with “naturally,” which they believe will facilitate the creation of resilient and comfortable societies. HCT researchers believe that the key to understanding natural human interactions lies in how humans “read ambience.” Reading ambience is the process through which a social actor identifies and acts on the aspects of its self and surroundings that inform it of what behaviors are appropriate in a given setting. They work to reverse engineer how humans read ambience to create technologies that humans can interact with naturally. This dissertation argues that HCT researchers efforts to understand humanness through reverse engineering elucidate dimensions of human relations that have been suppressed in conventional discourses on the human. Anthropological understandings of the human have been predicated on the notion that the human is a form of life. Instead, HCT researchers’ work shows that the human is a system of communication. The human is defined by how it interfaces and exchanges messages with other systems of communication. Their perspective shows the human as a system defined by the relations it maintains among its body, its social and material surroundings, including technologies and other humans. By following HCT researchers’ attempts to create human-machine interfaces, this ethnography attempts to offer an approach to the human based in communication that challenges atomistic understandings of the human still latent in anthropology.

Keywords: Communication
Japan
Robotics
Technology
Value
Wearables
Advisor: Satsuka, Shiho
Society and Warfare in Lombard Italy (c. 568–652)

The aim of this dissertation is to re-evaluate the role of warfare and the military from the establishment of the Lombards in Italy to the end of King Rothari’s reign (c. 569–652). A thorough reassessment of the source material suggests that the Lombard kingdom was a breakaway section of the Byzantine army in northern Italy, which, seceding from the Empire, produced an independent government in Italy. Chapter one analyzes the evidence connecting the advent of the Lombards in Italy with a military rebellion, and produces a picture of the social context of the army in the 560s, highlighting the reasons behind the rebellion and the connections between mutiny and barbarian gentes. Chapter two tackles the trajectories of the Lombard policy after the rebellion, the role of Kings Alboin and Cleph, and the collapse of the Lombard monarchy (c. 574—84). Chapter three analyzes the role of the Franks in the re-establishment of the Lombard monarchy, and the importance of northern Italy for Frankish Alpine policy. The fourth chapter covers the period from Agilulf to Rothari examining the political and military achievements of Agilulf and Rothari, and evaluating the changes in the performance of the army, to suggest that the social conditions behind the support of the army had changed from the early to the mid seventh century. The social aspects of the army in the seventh century are discussed in chapter five, which looks at Italian society under Lombard rule, analyzing the evolution of economy and social organization, and the impact of the military on society. Finally, chapter six uses the data on the performance of the army and on the social structure presented in the previous chapters, to provide an analysis of the mechanisms of recruitment and the impact of military policy and changes on Italian society under the Lombards.

Keywords: Early Middle Ages
Late Antiquity
Lombard Italy
Warfare
Advisor: Everett, Nicholas
Electron Transfer, Vibrational Coherence and Intrinsic Dopants in Conjugated Polymer/fullerene Blends

In this thesis, we utilize two-dimensional electronic spectroscopy (2D ES) to study the photoexcited dynamics in conjugated polymer/fullerene blends. A model system, poly(3-hexylthiophene) (P3HT) /PCBM blends was chosen in these studies. Three topics—ultrafast electron transfer, vibrational coherence and dynamics of intrinsic doped electrons are investigated. In conjugated polymer/fullerene blends, the mechanism for ultrafast electron transfer, preceding or in the meantime of vibrational relaxation remains a puzzle. By utilizing 2D ES, we report dynamics maps showing the pathways of charge transfer that clearly expose the significance of hot electron transfer. We observe vibrational coherence is directly transferred from the P3HT exciton to the P3HT hole polaron in the crystalline domain. This result suggests that the wavefunction of the P3HT cation exhibits a similar spatial extent as the photogenerated exciton. To further explore vibrational coherence, we propose a protocol that utilizes 2D coherence amplitude maps to separate the vibrational coherence from ground- and excited- electronic states. By applying this method to the P3HT film, we find that the vibrational coherence from excited electronic states has a dephasing time of ~ 244 fs. The long dephasing time of the vibrational coherence suggests that it might be involved in the electron transfer process in P3HT/PCBM blends. By using the vibrational coherence, we identify a photoinduced absorption band from 640 to 690 nm that could at least partially be attributed to the absorption of the charge-transfer product. We find that a fraction of the charge-transfer states are generated by either direct photoexcitation or rapid electron transfer within 30 fs. Furthermore, we also observe the spectral signatures of intrinsic doped electrons, i.e. anions, in P3HT domains in both steady-state absorption and 2D ES. We find that the anion does not quench excitons or charges in the first 400 fs.

Keywords: Conjugated polymers
Electron transfer
Intrinsic dopant
Organic photovoltaics
Ultrafast spectroscopy
Vibrational coherence
Advisor: Scholes, Gregory D
The Central Role of RMTg GABA Neurons in Morphine-induced Locomotion

Opioids have strong analgesic and rewarding effects, but these can often lead to addiction and dependence. Recently, the rostromedial tegmental nucleus (RMTg) has been identified as a key input that opioids act upon. This thesis demonstrates, through a variety of behavioural and anatomical techniques, how RMTg GABA and dorsal tegmental acetylcholine (ACh) neurons work together to control opioid locomotion. In the first studies, a Herpes simplex viral vector (HSV) was utilized to transfect the excitatory muscarinic M5 receptor gene into either the ventral tegmental area (VTA) or RMTg of wild-type or M5 knockout mice. HSV-M5 transfections in the VTA increased morphine locomotion while RMTg transfections completely suppressed the activity. Retrograde tracers injected into RMTg or VTA, showed that many LDT and caudal PPT cholinergic neurons project to both RMTg and VTA; further, inhibitory M4 muscarinic receptors were localized to the RMTg. To selectively control RMTg GABA neurons, GAD2::Cre mice and Cre-dependent-AAVs containing either the excitatory (M3D) or inhibitory (M4D) designed receptors were utilized. M3D excitation of RMTg GABA neurons blocked morphine-induced locomotion, while M4D inhibition strongly increased the locomotion. Based on this work, a new model proposes how mesopontine cholinergic neurons and muscarinic receptors in the RMTg and VTA are important for DA-dependent and DA-independent opioid-induced rewards. Cholinergic inhibition of RMTg GABA neurons via M4 muscarinic receptors facilitates opioid inhibition of the same critical neurons. Many of the same LDT and caudal PPT cholinergic neurons also connect with VTA DA neurons via excitatory M5 muscarinic receptors that facilitate DA-dependent rewards and locomotion. This thesis demonstrates the importance of the RMTg and cholinergic mechanisms in mediating opioid locomotion, and suggests how locomotion and reward work through both DA-dependent and DA-independent pathways.

Keywords: DREADD
HSV
locomotion
morphine
rostromedial tegmental nucleus
ventral tegmental area
Advisor: Yeomans, John S
Teacher Education for Democracy in Post-Soviet Ukraine

Teacher education can enable or impede democratic socialization of prospective teachers through the provision (or not) of knowledge, skills, and values necessary for democratic teaching and effective functioning in democratic society. This dissertation investigates teacher education for democracy in post-Soviet Ukraine. It examines contextual factors that enable and impede teacher education practice for democracy, teacher educators’ conceptions of democracy and citizenship, and their enactment of these concepts in practice, in four universities in western, central, and eastern Ukraine. The study employs a mixed method multiple-case study methodology: case study profiles of four democratically oriented teacher educators, each working at a different university, are contextualized through background interviews, surveys of additional teacher educators, and document analysis. It illuminates political, cultural, and pedagogical dimensions of democratic citizenship education in an ostensibly post-authoritarian context. Survey findings reveal that, despite some changes, teaching approaches remained predominantly transmissional, and most teacher educators did not emphasize the promotion of political and cultural dispositions such as active citizenship, personal responsibility, civic patriotism, or tolerance of other viewpoints, nations, ethnicities, and cultures. Preparation of teacher candidates to function in a democracy was obstructed by multiple societal, institutional, and personal factors. This study demonstrates the value of considering such factors, in order to understand the challenges of implementing education for democracy in non-Western, transforming contexts. Case studies of four exemplary teacher educators shed light on pedagogical and content dimensions of teacher education for democracy that were possible, although by no means typical, in this context. Their pedagogy departed from the dominant reliance on transmissional teaching and steeply hierarchical teacher-student relationships. Their course content promoted citizenship responsibility and a non-fearful mentality instead of paternalism and culture of fear; ethnic, racial, gender, and interregional tolerance instead of ethnocentrism; civically rather than ethnically oriented national pride and patriotism; and student-centered instead of solely teacher-centered pedagogies. The study contributes to comparative international research on education for democracy by providing practical examples of teacher education for democracy in a post-authoritarian context and by showing that Western-based typologies of democratic citizenship education can acquire different meanings, relevance, and significance in transitioning contexts such as Ukraine.

Keywords: democracy
democratic citizenship
post-authoritarian society
post-Soviet transition
teacher education
Ukraine
Advisor: Bickmore, Kathy
The Role of Pdxdc1 in Modulating Prepulse Inhibition of the Acoustic Startle Reflex in Mice

Prepulse inhibition of the acoustic startle reflex (PPI) is a common measure of sensorimotor gating that is abnormal in many neuropsychiatric diseases including schizophrenia. Current treatments for schizophrenia share a common mechanism of blocking the dopamine D2 receptor. However, existing antipsychotic medications are ineffective for many patients and cause severe side effects. Better medications are needed, and identifying new potential treatment targets is the first step in improving outcomes for this debilitating illness. Deficits in PPI can be improved by existing antipsychotic medications used to treat schizophrenia. I sought to identify novel molecular modulators of PPI, reasoning that these could be new treatment targets for schizophrenia. To accomplish this, brain mRNA transcript levels were correlated with PPI in six different strains of inbred mice with a range of PPI levels. Although many brain areas are involved in PPI, the hippocampus, striatum and brainstem were the three areas examined. Affymetrix MOE 420 microarrays were used to measure mRNA transcript levels and transcripts that best correlated with PPI were selected for verification using real-time RT-PCR. Pyridoxal-dependent decarboxylase domain containing 1 (Pdxdc1) encodes a 787aa putative pyridoxal-dependent decarboxylase, and was selected for further study because of a strong negative correlation of transcript abundance with PPI. I measured the distribution of Pdxdc1 mRNA and protein expression in mouse brain using in situ hybridization and immunohistochemistry, respectively, and found relatively strong expression levels of both molecules in the hippocampus. The functional role of Pdxdc1 in modulating PPI was verified by knocking down protein in the mouse hippocampus in vivo. Stereotactic injection of lentivirus containing a plasmid coding for anti-Pdxdc1 shRNA into the dentate gyrus of the hippocampus significantly increased PPI in male C57BL/6J mice. shRNA-mediated interference reduced Pdxdc1 protein levels by 30% and increased PPI by approximately 15%, without substantially altering spatial learning and memory-related behaviours, but with some effect on spontaneous locomotor activity. This suggests that Pdxdc1 may modulate PPI and warrants further study as a potential target for drug development.

Keywords: Hippocampus
Mice
microarray
Pdxdc1
Prepulse inhibition
RNAi
Advisor: Wong, Albert HC
Foreign Trained Black Lawyers’ Experiences in Ontario: I am a Lawyer! Am I a Lawyer? An Odyssey!

Abstract This thesis examines the experiences of foreign trained black lawyers navigating the Canadian legal credentialing process in Ontario and how that has impacted their lives. I chose to focus on foreign trained black lawyers (FTBL) and take a comparative look at black lawyers born and trained in Africa and the Caribbean as well as Canadian born blacks who studied outside Canada. FTBL includes those who are born in Canada and study abroad and those who are immigrants to Canada. The research employed a discursive framework, using the intersectionality of critical race theory and integrative anti-racist theory to contextualize and examine the issue. I employed a mixed method design using an online survey and interviews to examine and analyze the challenges of foreign trained black lawyers becoming credentialed in the Ontario legal system. The five major themes that emerged are as follows: 1) the NCA’s (National Committee on Accreditation) lack of transparency and consistency in the process of accreditation, and the Law Society of Upper Canada, specifically the LSUC exams; 2) Articling in Ontario, focusing on the challenges of securing articling positions; 3) the Impact of Racism, focusing on disempowerment and discrimination;4) Resilience and Career motivation, highlighting the participants’ coping mechanisms, sustenance and support; and 5) Networking, in particular relating to the importance and relevance of social capital in finding suitable work experiences.

Keywords: Critical Race Theory
Foreign trained Black Lawyers
Integrative anti-racist theory
Internationally trained or Educated Lawyers
Lawyer Licensing in Ontario
Legal training
Accreditation and Credentialing in Ontario
Advisor: Wane, Njoki N