VictorJuiz/thesis huggingface dataset:
Identification and Characterization of the Receptor for the Soluble Fibrinogen Like Protein 2 (FGL2)

The multi-functional FGL2 can be expressed as either a type II membrane-associated glycoprotein or a secreted tetrameric molecule. As an important effector of regulatory T cells, secreted FGL2 inhibits dendritic cell maturation and T cell proliferation. The mechanism of its immunomodulatory function remains unclear. The goals of this thesis are to identify receptor(s) of secreted FGL2, key biological functions and signaling pathways, and mechanism of FGL2 oligomerization. Soluble FGL2 was critical for all studies, and the production of recombinant FGL2 was compared in E. coli, insect cells and mammalian cells. Soluble and stable FGL2 was secreted only by mammalian cells, indicating the importance of post-translational modification. In flow cytometry and surface plasmon resonance assays, recombinant FcFGL2 and albumin tagged FGL2 fusion proteins bound to Fc gamma RIIB and Fc gamma RIII receptors expressed by antigen presenting cells (APCs), including lipopolysaccharide (LPS)-stimulated B lymphocytes, endothelial cells, thioglycollate-stimulated peritoneal macrophages, and bone marrow-derived dendritic cells (BM-DCs). The binding of recombinant FGL2 to Fc gamma RIIB and Fc gamma RIII was specific, dependent on receptor expression and blocked by anti-Fc gamma RIIB/III antibody. FcFGL2 inhibited the maturation of BM-DC derived from fc gamma riib wild type mice but not from fc gamma riib knock out mice. It also induced apoptosis of the A20 mouse B cell line (Fc gammaRIIB+), but not the A20IIA1.6 cell line (Fc gamma RIIB-). The activation of caspases induced by FcFGL2 binding to A20 cells was confirmed by flow cytometry, Western blotting and analysis of DNA fragmentation. The role of Fc gammaRIIB in FGL2-mediated immunosuppression was confirmed in vivo. Infusion of FcFGL2 into fc gamma riib+/+, but not fc gamma riib-/- C57BL/6J mice (H-2b) inhibited the rejection of fully mismatched BALB/cJ (H-2d) skin and heart allografts. Studies on the mechanism of FGL2 oligomerization employed site-directed mutagenesis and revealed that cysteines at positions 94, 97, 184, and 187 were critical. Mutation of these cysteines resulted in secretion of monomeric FGL2. Computer modeling of FGL2 tetramers predicted an asymmetric arrangement that was similar to the structure of multimeric ficolin. The data presented in this thesis provide mechanistic insights into the immunosuppressive activity of soluble FGL2, and a foundation for the development of a novel and potentially highly effective immunosuppressive therapy.

Keywords: fibrinogen like protein 2
immunoregulation
Advisor: Levy, Gary A.
Iphigenia at Aulis: Myth, Performance, and Reception

When Euripides wrote his final play, Iphigenia at Aulis, depicting the human sacrifice of Agamemnon’s first child that allowed the sailing of the Greek expedition against Troy, he was faced with several significant mythographic choices. Of primary concern was the outcome of the sacrifice: there existed a strong tradition in early sources that mitigated the sacrifice by affecting a divine rescue by Artemis, usually with a deer being left in her place on the altar. The extremely troubled textual history of our script – the play was first performed posthumously, and we do not know in what state Euripides left the text – means that we cannot be certain which tradition Euripides actually chose to follow, sacrifice or rescue. Depicting Iphigenia as a willing victim, however, must have been Euripides’ own innovation. This dissertation explores the ramifications of that self-sacrifice and contextualizes this play within a tradition of mythographic evolution and reception. Chapter 1 surveys the history of criticism of the text, itself a mode of reception, and also examines trends in Euripidean criticism in the modern period, limited until recently by the textual issues. Chapter 2 considers instances of the Iphigenia legend before Euripides’ play. The parodos of Agamemnon, the first source to express the sacrifice in terms of human suffering, receives special attention. Chapter 3 seeks to understand audience reception at the moment of first performance through three different critical lenses: thematic (self-sacrifice was a recurring motif in Euripides’ work), socio-political (by considering the recurring Panhellenic sentiment deployed in the play’s rhetoric), and dramaturgical (by treating the spatial dynamics of the performance as a point of intertextual contact). Chapters 4 and 5 examine reception of the sacrifice story in antiquity (in the Hellenistic and Roman periods), a process which reveals much about the position of Greek tragedy in the popular imagination following the fifth century. The final chapter brings to bear considerations of adaptations of the play into new genres and new media since the advent of the printing press, all of which open up new possibilities for the creators of these adaptations and the story they wish to tell.

Keywords: Iphigenia
Euripides
Greek Drama
Awesome
Advisor: Revermann, Martin
Salvator Rosa as 'Amico vero': The Role of Friendship in the Making of a Free Artist

The seventeenth-century Neapolitan painter and satirist Salvator Rosa (1615-1673), long regarded as a harbinger of the ideals of professional independence that characterize the artists of the Romantic era, is here returned to the social circumstances of his own time. This dissertation argues that Rosa’s personal and professional identity of autonomy and his pursuit of an original, distinctive persona were facilitated by male friendship. A key component of the philosophical ideal to which Rosa and his friends subscribed, friendship is defined by a standard of egalitarianism that permits its practitioners to be at once dependent and independent. In his adoption and cultivation of the rituals and discourses of friendship – especially academic friendship – Rosa found a strategy for navigating the obligatorily socially-delineated parameters of self-fashioning in seicento Florence and Rome. Friendship permeated the most vital elements of Rosa’s career: his early theatrical practice in Rome, his private academy in Florence, and his business tactics as a painter and printmaker in Rome. This dissertation aims to open up an area of insight into Rosa as both unique among and representative of his contemporaries, and to expand upon the existing scholarly knowledge of an artist on the cusp of an important development in the history of the visual artist’s identity.

Keywords: Rosa, Salvator
friendship
identity
performance
autonomy
academy
sociality
painting
printmaking
satire
Advisor: Sohm, Philip
Decision-making and Self-regulation from a Social-personality Neuroscience Perspective

Pitting long-term goals against short-term desires is among the most difficult tasks in human decision-making. According to behavioural and neuroeconomic theories of self-regulation, these decisions involve a competition between “hot” reward-focused impulses and “cool” cognitive control mechanisms. The current dissertation examines this topic from the perspective of social and personality neuroscience, exploring the cognitive and affective dynamics underlying the self-regulatory process. Chapters 1 and 2 explore how the “hot” system is dispositionally expressed in the personality trait of Extraversion, and the implications of this finding for decision-making behaviour. Turning to the “cool” system, Chapter 3 examines the role of effective performance monitoring in predicting real-world self-regulatory outcomes. Finally, Chapter 4 addresses the question of whether self-regulatory performance can be improved, reporting the effects of a goal-setting intervention on long-term decision-making. Results across the studies are discussed within an integrative model of self-regulation, situated within a social-personality neuroscience framework.

Keywords: Decision-Making
Self-Regulation
Social Neuroscience
Personality
Delay of Gratification
Advisor: Peterson, Jordan
Application of an Endothelialized Modular Construct for Islet Transplantation

Successful survival of large volume engineered tissues depends on the development of a vasculature to support the metabolic demands of donor tissue in vivo. Pancreatic islet transplantation is a cell therapy procedure to treat Type 1 diabetes that can potentially benefit from such a vascularization strategy. The treatment is limited as the majority of transplanted islets (60%) fail to engraft due to insufficient revascularization in the host(1, 2). Modular tissue engineering is a means of designing large volume functional tissues using micron sized tissues with an intrinsic vascularization. In this thesis, we explored the potential of endothelialized modules to drive vascularization in vivo and promote islet engraftment. Human endothelial cells (EC) covered modules were transplanted in the omental pouch of athymic rats and human EC formed vessels near implanted modules until 7 days when host macrophages were depleted. Rat endothelial cells covered modules were similarly transplanted in the omental pouch of allogeneic rats with and without immunosuppressants. When the drugs were administered, endothelialized modules significantly increased the vessel density. Moreover, donor GFP labelled EC formed vessels that integrated with the host vasculature and were perfusable until 60 days; this key result demonstrate for the first time that unmodified primary endothelial cells form stable vessels in an allograft model. Transplantation of islets in such endothelialized modules significantly improved the vessel density around transplanted islets. Donor endothelial cells formed vessels near transplanted islets in allogeneic immunesuppressed recipients. Meanwhile, there was an increase in islet viability with transplantation of endothelialized modules in syngeneic recipients but this difference was not significant. In summary, endothelialized modules were effective in promoting stable vascularization and improving transplanted islet vascularisation. Future work should promote faster maturity of donor vessels and modulate the host immune and inflammatory responses to significantly improve transplanted islet engraftment.

Keywords: Vascularization
Tissue Engineering
Islet Transplantation
Endothelial Cells
Advisor: Sefton, Michael
Characterization of Inositol Transporters as a Method for Drug Delivery to the Centra Nervous System

A challenge in the treatment of central nervous system (CNS) diseases is the transport of drug candidates into the brain. Inositol stereoisomers have show promise as therapeutic agents for CNS disorders. scyllo-Inositol was an effective prophylactic and therapeutic for Alzheimer’s disease (AD) in TgCRND8 mice, a model of AD. This suggests inositol stereoisomers have excellent CNS bioavailability. They enter the brain through inositol transporters, of which there are three: one hydrogen myo-inositol transporter (HMIT) and two sodium myo-inositol transporters (SMIT1, SMIT2). HYPOTHESIS: Given the high CNS bioavailability of inositol stereoisomers, it may be possible to use inositol transporters to shuttle other compounds into the CNS. OBJECTIVES: 1. To confirm the CNS bioavailability of the two main inositol stereoisomers, myo- and scyllo-inositol, in both TgCRND8 and wild-type mice. 2. To examine inositol transporter expression in the brains, as a function of time and disease pathology, in both groups. 3. To evaluate the flexibility of the inositol transporters for transporting compounds by determining the substrate structural features required for active transport. RESULTS: myo-Inositol and scyllo-inositol accumulated in the brain following oral administration. Disease pathology did not alter baseline inositol levels or uptake. Brain subregional transporter expression was unaltered as a function of age or disease pathology. In vitro cell culture experiments found HMIT inactive and therefore not a contender for drug transport. In contrast SMIT1 and SMIT2 were both active and competitive transport assays, revealed distinct criteria for active transport through each system. However, both were stringent in the substitutions to the structure of myo-inositol possible to maintain active transport. CONCLUSION: Active transport through the inositol transporters is very sensitive to changes in the structure of myo-inositol and only conservative changes are possible. Therefore, these transporters would not make effective shuttling systems for drug transport into the brain.

Keywords: Neuroscience
Alzheimer's disease
Advisor: McLaurin, JoAnne
Textual Integrity and Coherence in the Qur'an: Repetition and Narrative Structure in Surat al-Baqara

This study addresses the riddle of al-Baqara’s internal organization, utilizing new insights from literary theory and Biblical Studies to identify the sura’s structure and unifying themes. It also explores the possible added value in approaching al-Baqara as a whole compositional unit, as opposed to a conglomeration of isolated verse-groups. The dissertation begins with a historical overview of coherence-related approaches, commencing with the classical naẓm- and munāsaba-discourses as observed in the writings of Jāḥiẓ, Bāqillānī, Biqā῾ī and others, and extending to the modern period and the work of scholars such as Amīn Aḥsan Iṣlāḥī, ῾Abd al-Muta῾āl al-Ṣa῾īdī, and Matthias Zahniser. This overview is followed by a discussion of methodology, locating this study within the reader-oriented, synchronic, intertextual approaches, and showing methodological parallels with Biblical Studies. A new reading framework for the sura is developed, utilizing in part some of the theories of the Russian literary theorist and philosopher, Mikhail Bakhtin. The sura’s structure is identified by means of analyzing its distinctive repetitions, a known structuring device in oral texts. Incremental inclusios, alternations and chiasms delineate al-Baqara’s compositional subunits. The overall structure of the sura emerges as chiastic, following the pattern ABC/B’C’A’/C’’B’’A’’, where A is a section having the character of a test, B a section containing instructions and C a story portraying primeval origins. The repetitions are of increasing length, the general escalating character of the devices focusing attention on the last panel (C’’B’’A’’). In a first reading, the central theme is identified by means of the sura’s Leitwort, a leading keyword distinguished by its special location, high concentration and even distribution within the sura. Reading the sura for what it reveals about the deity, the Leitwort, ‘guidance’, indicates a common theme of ‘God as guide’. In a second reading, the sura is read for its pedagogical content and the central theme becomes ‘first lesson in the new religion’. The added value in approaching the sura as a whole, as a totality, is in seeing how each theme is progressively developed and elaborated by every one of the sura’s various panels and how these themes hold the sura together as a unit.

Keywords: Qur'an, Quran, Koran, Islam, Coherence, Surat al-Baqara
Advisor: Lawson, Todd
Domestic Dialogue: The Language and Politics of Adoption in the Age of Shakespeare

This dissertation examines the representation of adoption in early modern English drama in order to analyze the language of social and familial relations in early modern culture. I propose that although these plays often ultimately support the traditional idea of a birth family, adoption challenges conventional notions of the family by making artificial, non-consanguine relations appear natural, thereby exposing the family unit as a social construction. I suggest further that adopted characters complicate notions of biological inheritance through their negotiations of language, place, and power. My dissertation thus explores the connections between historical language use and social status in early modern England; it couples early modern rhetorical theories and treatises with modern linguistic theory, drawing upon recent sociolinguistic scholarship. The result is to show that understanding how language demarcates social position is essential to illuminating the cultural intricacies of the plays of the period. In Chapters 1 and 2, I investigate the social and economic repercussions of adoption. Chapter 1 discusses the previously overlooked cultural importance of horticultural metaphors of adoption in Shakespeare’s The Winter’s Tale, Cymbeline, and All’s Well That Ends Well. In this chapter, I explore the ways in which early modern culture explained adoption by depicting it in a particular kind of figurative language. Chapter 2 focuses on the economic consequences of, and motivations for, adoption in Middleton’s A Chaste Maid in Cheapside. In my final two chapters, I scrutinize the relations between the early modern family and linguistic practice. Chapter 3 explores the connections between genetics, physical likeness, and language in Lyly’s Mother Bombie and Shakespeare’s The Comedy of Errors. Finally, in Chapter 4 I investigate familial relation as a source of linguistic and social power. Middleton’s Women Beware Women, I argue, suggests that kinship exists within language and grants particular speakers linguistic and social authority.

Keywords: English Renaissance Drama
Shakespeare
Adoption
Advisor: Magnusson, Lynne
The Benefit of the Doubt: Regarding the Photographic Conditions of Conceptual Art, 1966-1973

This dissertation offers a reconsideration of the uses of photography under the aegis of Conceptual Art between 1966 and 1973 by analyzing the ways photography challenged epistemological limits, and, despite the claims regarding the medium’s inherent indexicality, emphasized experience over exactitude, and doubt in place of certainty. By focusing on four American practitioners, I argue for the “benefit of the doubt;” in other words, for the value of disbelief and hesitation, marking the reorientation of art at this time towards critical methods which oppose all orthodoxies, including but not limited to formalist dogmas, and instead are committed to the denial of autonomy in favor of understanding meaning as infinitely contingent. The dissertation is divided among four key case studies, including Mel Bochner (n. 1940), Bruce Nauman (n. 1941), Douglas Huebler (1924-1997), and John Baldessari (n. 1931). Each chapter argues for the unique contribution of photography in relation to conceptual art practices, while also situating the projects of these individual practitioners within the broader history of the medium of photography. I explore specifically the concepts of seriality, transparency and theory in Bochner; performance, “worklessness,” and failure in Nauman; portraiture, mapping and impossibility in Huebler; humor, didacticism, choice and chance in Baldessari. This project looks back continuously to significant precursors, in particular the work of Marcel Duchamp (1887-1968), as a means of engaging the status and function of art after the Readymade, particularly as concerns de-skilling, disinterest, affirmative irony, and nominalism, as well as the dialectic between inclusivity and inconclusivity.

Keywords: Photography
Conceptual Art
Advisor: Kaplan, Louis
Exploring Sources of Human and Environmental Fluorochemical Contamination

Perfluorinated carboxylates (PFCAs) and perfluorinated sulfonates (PFSAs) are found almost ubiquitously in the environment, however their direct production and use is limited. The focus of this thesis was to explore connections between observed contamination with the manufacture and/or use of commercial fluorochemical materials. Perfluorinated sulfonamides (PFSAms) are semi-volatile materials used in the manufacture of commercial fluorochemicals. Investigations into the atmospheric fate of a model PFSAm found atmospheric lifetimes that allow transport to remote environments, potentially through a novel N–dealkylation product. A suite of PFCAs, as well as the PFSA from loss of the amide moiety, were also observed. This investigation demonstrated that PFSAm atmospheric oxidation will contribute to PFCA and PFSA contamination in remote locations, including the Arctic. The perfluorinated phosphonates (PFPAs) were used as defoaming additives in pesticide formulations. Using novel extraction and analysis methods, widespread PFPA contamination was detected in Canadian surface waters and wastewater treatment plant (WWTP) effluent. As fully fluorinated acids, the PFPAs are a new class of perfluorinated acid discovered in the environment. Uptake and elimination parameters determined in the rat demonstrate the potential for human PFPA exposure, as these chemicals are bioavailable. Processes governing the pharmacokinetics and disposition of perfluorinated acids in the body are poorly understood. Novel heteronuclear nuclear magnetic resonance experiments identified human serum albumin as the major site of interaction. Competitive binding experiments found the PFCAs displaced the endogenous human serum albumin ligand, 13C1-oleic acid, at lower concentrations than established ligands. The strong association observed between the PFCAs and human serum albumin may inform observed human toxic endpoints and long elimination half-lives. The polyfluoroalkyl phosphates (PAPs) are used in food-contact paper packaging. High PAP concentrations were discovered in human sera, waste paper fibres and WWTP sludge, establishing human exposure to these chemicals. Biotransformation from PAP to PFCA was investigated in a rat model. The serum kinetics and PFCA products observed, suggest PAP exposure may be a significant source of human PFCA contamination. The concerted approach of environmental monitoring with investigations of atmospheric and biological fate allowed strong associations to be made between commercial fluorochemical sources and observed contamination.

Keywords: Environmental Chemistry
Fluorochemicals
Advisor: Mabury, Scott A.