VictorJuiz/thesis huggingface dataset:
Integrating High-throughput Technologies for the Identification and Validation of Novel Ovarian Cancer Biomarkers

Ovarian cancer is the most lethal gynaecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases significantly in late-stage diagnoses. The majority of cases are of epithelial origin, which can be classified into four major subtypes: serous, mucinous, endometrioid and clear cell carcinoma. Unfortunately, the clinically-approved markers for ovarian cancer - CA125 and HE4 alone - perform poorly for the mucinous, endometrioid and clear cell subtypes and thus, diagnosis of these subtypes remains a significant challenge. To this end, an integrated approach to ovarian cancer biomarker discovery was developed in this study through combining proteomics with other high-throughput platforms. Using proteomic analyses of ascites fluid from women with ovarian cancer and conditioned media of ovarian cancer cell lines, 15 high-priority candidates were identified as putative novel biomarkers using said integrated approach. Serum validation revealed two markers - folate receptor 1 and kallikrein 6 - to have comparable diagnostic ability to the clinically-approved markers, albeit with similar limitations in their ability to detect patients of the non-serous histotypes as well. Fortunately, the validation of the two in-house markers served as proof-of-principle of our integrated approach to biomarker discovery. As a result, the approach was employed on non-serous ovarian cancer tissues to identify novel markers specific to the mucinous, endometrioid and clear cell subtypes of ovarian cancer. Over 9000 unique proteins were identified in this exercise and with the use of an unbiased filtering algorithm based on transcriptomics and bioinformatics, a list of high-priority candidates for each subtype was generated. Several of the high-priority candidates have shown strong biological and molecular relevance to their respective subtypes, demonstrating the robustness and utility of the integrated approach. Future studies will need to investigate these candidates in independent serum cohorts to truly assess for their ability to diagnose their respective subtypes.

Advisor: Kulasingam, Vathany
Diamandis, Eleftherios P
Impostures: Subjectivity, Memory, and Untruth in the Contemporary Memoir

The memoir boom of the last two decades has seen record numbers of writers, readers, and critics engaging with forms of life narrative. At the same time, we have witnessed several cases of imposture, which Susanna Egan defines as “a serious disconnect between the author as a person alive in the world, pre-text, before any story emerges, and the written life…[Impostors] claim lives they have not lived, experiences they have not had, and identities that belong to other people” (3). I argue that impostures cannot simply be read as fiction upon their exposure: the referential claim persists in elements of the text itself, particularly in the (invented) name that authorizes the autobiographical truth claim. Thus, I frame imposture both as a genre of life narrative and in relation to the source genres it appropriates. Further, I identify the element of extratextual performance (the assumption of the imposturous persona in public venues such as readings and interviews) as crucial to contemporary imposture, connected to the critical and commercial demands of twenty-first century authorship. My first chapter revisits poststructuralism’s pronunciation of the author’s death and rereads Barthes and Foucault in conjunction with autobiographical theory to locate an author-figure produced by and within the autobiographical text, using Genette’s concept of the paratext as a threshold to position the author’s name as the hinge between text and world. I examine previous approaches to literary deception and suggest that a lack of attention to questions of power and difference makes them insufficient to account for imposture, particularly an imposturous claim to traumatic or marginalized experience. The next three chapters each address a set of impostures in the context of their source genres, respectively the Holocaust testimony (Wilkomirski, Defonseca, Rosenblat), the veiled bestseller (Khouri, Amina), and the abused child narrative (LeRoy). Each chapter situates its cases in relation to a contemporary theoretical discourse (traumatic memory, transnational feminisms, queer theory), emphasizing the dynamism of autobiographical discourse (even its imposturous variants) and the broader implications of my study for claims about the ethical value of life narrative and the ethical turn in literary studies as a discipline.

Keywords: Contemporary literature
Critical theory
Imposture
Life writing
Literary ethics
Subjectivity
Advisor: Ruti, Mari
Fluid Phase Measurement using Optical, Microfluidic and Nanofluidic Methods

Understanding fluid phase behavior is essential to a wide range of applications, including oil and gas recovery, chemical reactor engineering, transport and storage of natural gas and carbon dioxide, and supercritical fluid processing and extraction. In this thesis, novel experimental methods – optical, microfluidic and nanofluidic - are developed to measure and understand fluid phase behaviors for carbon dioxide transport/storage and shale gas/oil production. (i) Optical thin-film interference based bubble and dew point sensor probe: The sensor probe within a small pressure-volume-temperature (PVT) system offers accurate (

Keywords: critical point
microfluidic
nanofluidic
optical
phase behavior
phase change
Advisor: Sinton, David
'Remembered in the Body': Disability and Slavery in England and the Caribbean 1500-1834

This dissertation explores the constitutive relationship between disability, anti-black racism, and slavery in the English Atlantic World, from the early stages of colonization to the abolition of the slavery in 1834. It argues that Atlantic slavery, specifically the sugar- producing colonies of the English Caribbean, were key to the development of modern understandings of disability and the disabled body. It was in the specific historical context of the establishment of Englandâ s American colonies, the introduction of sugar to the European economy, and the rapid expansion of the slave trade that the English began increasingly to argue that blackness was an inheritable and racial form of monstrosity. This argument eventually served to normalize and mute opposition to African dispossession in the English Atlantic World. Plantation slavery in the English Caribbean was a disabling system of human exploitation and degradation. The processes of capture, forced march, imprisonment, and forced migration that characterized the slave trade, together with the hostile labour and living conditions of Caribbean sugar plantations, often resulted in emotional, psychological, sensory, and physical impairment. The slave laws of the English Atlantic World deliberately constructed the enslaved as both human and animal, and yet not fully either. By not resolving this tension between the human and the animal, lawmakers and slaveowners could recognize the humanity of the enslaved but effectively disable it by treating the enslaved like animals. The very real spectre of revolutionary emancipation in the eighteenth-century Atlantic World is key to understanding the place of disability in both anti- and pro-slavery rhetoric. Abolitionist representations of the supplicant, disabled bondsperson contrasted with whitesâ fear of the threatening, able-bodied, armed, black male revolutionary and anti-slavery rebel. These two images embodied different paths to emancipation â the choice between revolutionary and armed rebellion on the one hand, exemplified by the Haitian Revolution, and emancipation as a process of imperial and legislated reform on the other. This thesis attempts to retrieve a history of disability in the colonial Caribbean from the archive of English Atlantic slavery and demonstrate that concepts of monstrosity, race, disability, and enslaveability were inextricably linked during the colonial period.

Keywords: Atlantic World
Caribbean
Disability
England
Race
Slavery
Advisor: Newton, Melanie J
Design and Development of Fluorescent Sensors for the Detection of Proximally Phosphorylated Peptide and Protein Motifs

While protein phosphorylation is recognized as a chief regulator of protein activity, little is known about the significance of the relative spatial separation among the phosphorylated sites. Specifically, while proximal phosphorylation on two or more residues appears to be associated with disease, no simple methods for the detection of this motif are commercially available. To address this, we developed a simple yet robust chemosensory approach, whose selectivity for proximally phosphorylated motifs relied upon the stoichiometry of sensor binding. A single chemosensor molecule, consisting of a pyrene excimer-forming fluorophore and a phosphate-binding Zn2+-cyclen unit, was predicted to associate with a single phosphorylated site. Thus, a proximally phosphorylated motif would be capable of binding more than one sensor molecule bringing their pyrene units into close proximity, which in turn would induce measurable excimer fluorescence. The turn-on mechanism of the developed approach, and its non-covalent mode of action, enabled the application of this system towards the detection of proximally phosphorylated peptides and proteins in a variety of widely used research platforms. These include aqueous solutions, polyacrylamide gels, blotting membranes, microplate surfaces, as well as in cell imaging. A powerful feature of this approach in gel and blot assays, was its compatibility with additional downstream analyses using other stains as well as mass spectrometry. The signal detection could be achieved using standard equipment available to a majority of laboratories. In the course of this work we have extensively optimized this sensory system from the biophysical and chemical perspectives. Guided by the classical principles of molecular recognition, this thesis work yielded the most efficient chemosensory system for the detection of proximally phosphorylated proteins described to date, and adds significant value to the fields of fundamental phospho-proteomics, disease characterization and drug development.

Keywords: assays
Chemosensor
metal coordination
molecular recognition
Proximal phosphorylation
Pyrene
Advisor: Gunning, Patrick T
The Role of Type VIII Collagen in Fibrous Cap Formation and Progression of Atherosclerosis

Collagens play an integral role in the progression of atherosclerosis. Collagen synthesis and remodelling influence inflammation, smooth muscle cell (SMC) proliferation and migration, and properties such as plaque tensile strength and mechanical stability. Type VIII collagen is expressed at low levels in the arterial system however, it is dramatically up-regulated in atherosclerosis. The purpose of this thesis is to determine the role of type VIII collagen in the development of atherosclerosis. Our first study uses Col8+/+;Apoe-/- and Col8-/-;Apoe-/- mice on an atherogenic diet to illustrate that type VIII collagen plays a role in formation of the fibrous cap. Deletion of type VIII collagen resulted in reduced SMC and fibrillar type I collagen content and gelatinase activity. Reduced fibrous cap thickness and increased necrotic core size were observed in plaques from these mice. The second study shows that the advanced plaques from mice deficient in type VIII collagen have increased macrophage proliferation and accumulation. Increased features iii associated with plaque instability such as breaks in the elastic lamina and cleaved collagen content were also observed. Plaque stiffness was reduced in Col8-/-;Apoe-/- mice, suggesting that type VIII collagen plays a role in the mechanical integrity of the plaque. In the third study, we use a bone marrow transplantation model to generate chimeric mice with myeloid-specific deletion of type VIII collagen (Col8-/-ď  +/+). We show that plaques from Col8-/-ď  +/+ mice have reduced elastin content compared to control mice. Finally, preliminary work suggests a role for type VIII collagen in the expression of fibrillar collagens. Plaques from Col8-/-;Apoe-/- mice show reduction of type I and III collagen accumulation and a reduction in type III collagen expression is observed in SMCs from Col8-/- mice. In summary, the studies presented here suggest that type VIII collagen confers increased plaque stability by promoting SMC infiltration and fibrosis as well as reducing inflammation. This work underscores the

Keywords: Atherosclerosis
Cell biology
Collagen
Matrix remodelling
Type VIII collagen
Advisor: Bendeck, Michelle P
The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype

In this study the role of the chondrocyte cytoskeleton in regulating cellular mRNA levels in chondrocytes was examined. Passaging of chondrocytes in traditional 2D monolayer culture results in chondrocyte dedifferentiation. As compared to primary chondrocytes, passaged cells exhibited a lower g-/f-actin ratio. However tubulin polymerization was not significantly altered by passaging. Pharmacological actin depolymerization partially redifferentiated passaged chondrocytes whereas modulation of tubulin did not. To delineate the mechanism by which actin polymerization regulates gene expression, myocardin related transcription factor A (MRTF) signaling was investigated. Passaging resulted in an increased amount of MRTFa as well as a predominantly nuclear localization of MRTF; these changes occurred within 5 days of culture and were sustained in passaged chondrocytes. Plating passaged cells in high density 3D or in suspension on top of agarose or exposure of cells in monolayer culture to latrunculin B resulted in increased g-/f-actin, cytoplasmic localization of MRTFa, and fibroblast matrix (col1 and tnc) mRNA levels. Exposure of chondrocytes to MRTFa inhibitor (CCG1423) resulted in only small changed to cell shape did not significantly affect gene expression but did result in reduced fibroblast matrix gene expression. siRNA mediated MRTF knockdown mimicked some but not all effects on gene expression as actin depolymerization. In addition SRF knockdown did not completely mimic MRTF knockdown. This demonstrated that actin could utilize several different signaling mechanisms to regulate gene expression. Although actin depolymerization did not completely redifferentiate passaged chondrocytes, it appears to be a potent regulator passaged chondrocytes gene expression and initiates the redifferentiation process.

Keywords: Actin
Bioengineering
Cartilage
Chondrocyte
Dedifferentiation
MRTF
Advisor: Kandel, Rita A
Colonization and the Church in High Medieval Sardinia

This thesis investigates the role that the Church played in the political, spiritual and economic colonization of Sardinia in the high Middle Ages. By using Robert Bartlett’s conception of the European “center” and “periphery,” it shows that Sardinia represents an unusual case of a territory that was culturally both central and peripheral. Within this ambiguous cultural setting, and using papal letters, political treaties, chronicles, monastic documents, and onomastic evidence, the thesis examines the way Pisa, Genoa and the Roman pontiffs used Rome’s spiritual and cultural authority to strengthen their own political and economic claims in Sardinia. Specifically, by focusing on the archbishop of Pisa and the bishops and archbishops of Sardinia, it shows that the personnel of the Church, which are not commonly considered agents of colonization in Sardinia, were in reality fundamental to bringing Sardinian society closer to being a political and cultural extension of the Italian mainland. It also, however, investigates the ways in which local Sardinian rulers at times strongly resisted ecclesiastical pressures to conform to the norms of Rome, or used the spiritual prestige and cultural tools offered by the Roman Church to negotiate political advantages for themselves. In this way, the thesis finds that foreign cultural colonization in Sardinia was at times less effective than is generally assumed, and that in certain situations the personnel of the Sardinian Church could offer the means for resistance to foreign colonization. Finally, the thesis draws comparisons between Sardinia and other examples of political, economic and spiritual colonization within Europe, to show how Sardinia is both part of a wider medieval European pattern, and simultaneously a unique case in the study of medieval colonization.

Keywords: Bishops
Church
Colonization
Italy
Mediterranean
Sardinia
Advisor: Goering, Joseph
Meyerson, Mark
Truth and Truthmaking in 17th-century Scholasticism

Some propositions are true and others are false. What explains this difference? Some philosophers have recently defended the view that a proposition is true because there is an entity, its truthmaker, that makes it true. Call this the ‘truthmaker principle’. The truthmaker principle is controversial, occasioning the rise of a large contemporary debate about the nature of truthmaking and truthmakers. What has gone largely unnoticed is that scholastics of the early modern period also had the notion of a truthmaker [verificativum], and this notion is at the center of early modern scholastic disputes about the ontological status of negative entities, the past and future, and uninstantiated essences. My project is to explain how early modern scholastics conceive of truthmaking and to show how they use the notion of a truthmaker to regiment ontological enquiry. I argue that the notion of a truthmaker is born of a certain conception of truth according to which truth is a mereological sum of a true mental sentence and its intentional object. This view entails the truthmaker principle and is responsible for some surprising metaphysical views. For example, it leads many early modern scholastics to posit irreducible negative entities as truthmakers for negative truths, giving rise to an extensive literature on the nature of negative entities. In order to find truthmakers for the so-called eternal truths, such as ‘A human being is an animal’, some philosophers claim that individual essences distinct from and independent of God necessarily have being from eternity. Other early modern scholastics reject these extravagant views; they argue that only positive, present tense truths are made true by existing things. This view is motivated jointly by (i) a distinctive theory of truth bearers, (ii) a common sense view of the truth conditions for negative, tensed, and modal truths, and (iii) the idea that truths are about their truthmakers. I argue that this view has significant philosophical consequences and should be attractive to those who think both that truth is grounded in being and that not every truth has a truthmaker.

Keywords: Early Modern Scholasticism
Francisco Peinado
Thomas Compton Carleton
Truth
Truthmaker
Advisor: PickavĂŠ, Martin
The Santissima Annunziata of Florence, Medici Portraits, and the Counter Reformation in Italy

A defining feature of the Counter-Reformation period is the new impetus given to the material expression of devotion to sacred images and relics. There are nonetheless few scholarly studies that look deeply into the shrines of venerated images, as they were renovated or decorated anew during this period. This dissertation investigates an image cult that experienced a particularly rich elaboration during the Counter-Reformation – that of the miracle-working fresco called the Nunziata, located in the Servite church of the Santissima Annunziata in Florence. By the end of the fifteenth century, the Nunziata had become the primary sacred image in the city of Florence and one of the most venerated Marian cults in Italy. My investigation spans around 1580 to 1650, and includes texts related to the sacred fresco, copies made after it, votives, and other additions made within and around its shrine. I address various components of the cult that carry meanings of civic importance; nonetheless, one of its crucial characteristics is that it partook of general agendas belonging to the Counter-Reformation movement. That is, it would be myopic to remain within a strictly local scope when considering this period. The evidence nonetheless also demands more than a simple broadening of “context”. This thesis shows that key aspects of the material articulation of the Nunziata’s cult were deeply integrated with actions and attitudes emanating from the Church’s policy centres, in particular, Rome and Milan. At the same time, the sanctuary was a chief site for the expression of the power and privilege of the Medici, who were the ruling family of Florence and most prominent patrons of the fresco’s cult. My study therefore accounts for the intertwining of two strains of representation --the Medici as ideal Counter-Reformation princes and the Santissima Annunziata as a powerful miracle-working image.

Keywords: Annunziata
Counter Reformation
Florence
Medici
Portraits
Advisor: Sohm, Philip L
Circadian Factors in Coping with Chronic Stress

Circadian rhythms, cyclic changes that repeat approximately once every 24 hours, regulate daily temporal processes of physiology and behaviour in all living organisms. Rhythmicity is adaptive, providing advantages for survival, growth, and reproduction. For human beings, this includes rhythmic regulation of mental, physical, and emotional responses to stressors. In this dissertation, we addressed how human beings facing major stressors such as chronic disease (in this case, cancer), are influenced by circadian timing, specifically chronotype and sleep quality. A broad epidemiological study was conducted among individuals in different roles (patients, medical staff, and familial caregivers) facing a common stressor to assesses their ability to cope with the situation. Breast cancer patients provided real-time reports of their coping across the day. Patients and familial caregivers completed retrospective average ratings for their coping across the day across treatment, along with details on use of coping behaviours. Oncology staff provided ratings of their burnout, and Professional Quality of Life (ProQoL). These data were all assessed in relation to chronotype and sleep quality, and to an extent, in relation to personality. Chronotype and sleep quality influenced coping within each group, but their impacts were not correlated. Nonetheless, working at chronotypically optimal times improved ProQoL. ‘In the moment’ coping ratings from patients reflected their chronotype, as did their recalled coping. ‘Openness’ was positively linked with ProQoL among staff, and with an engagement coping style among patients and caregivers. The data reflect an influence of circadian timing on the expression of coping responses during chronic stress. A better understanding of changes in coping ability as they relate to one’s innate rhythms will allow for the development of a cognitive and emotion-based chronotherapy regime intended to maximize proactive coping among individuals facing chronic stress, such as providing care or undergoing treatment for cancer.

Keywords: Chronic Stress
Chronotype
Circadian Rhythms
Coping
Personality
Sleep Quality
Advisor: Ralph, Martin R.