VictorJuiz/thesis huggingface dataset:
The Poetic Tradition of Anglo-Saxon Riddles

The Exeter Book contains the only extant collection of Old English riddles. Behind this solitary witness, however, there lies a lost tradition of vernacular riddles, the nature of which can be inferred from a study of its relation to the Latin tradition of aenigmata. For unlike the Old English riddles, Latin aenigmata survive in numerous collections, both anonymous and by identified authors. The main contention of this dissertation is that the Old English poetic genre as represented by the Exeter Book Riddles can be best understood in the context of the composition, development, and transmission of Latin aenigmata. There were two reasons, I contend, for the popularity and rhetorical development of verse aenigmata in England: the first was because the genre had emerged to teach the composition of Latin poetry; and the second because the riddle itself is an inherently competitive, participatory form of verbal expression. These two aspects of the Latin genre led to a series of Anglo-Saxon poets composing aenigmata, many of which were rhetorically ornate poems. These aenigmata inspired the poetic form of Old English riddles and are the best evidence for their development and transmission in Anglo-Saxon England. Unlike previous studies, this dissertation goes beyond the authors of aenigmata to consider through close examination of individual manuscripts the contributions of the scribes and glossators who transmitted their collections from the seventh to the eleventh century. For they were active participants in this competitive literary tradition, even adding their own riddles to the collections that they copied. This is the first study to consider each manuscript as a separate witness to the Latin tradition. It is my contention that the Exeter Book Riddles similarly emerged out of such a collaborative tradition in Old English. The two aspects of the Latin aenigmata—teaching versification and the participatory nature of the riddle—were inherited by Old English poets and scribes, who composed rhetorically ornate riddles and participated in a competitive riddle tradition like their Latin counterparts. Studied in this way, the Exeter Book reveals the traces of what was once a dynamic poetic tradition of Old English riddles.

Keywords: Aenigmata
Enigmata
Exeter Book
Latin
Old English
Riddles
Advisor: Healey, Antonette diP
McDougall, Ian
The M region of α-Catenin Cooperates with Canoe, Ajuba, Vinculin and α-Actinin to Support Adhesion During Drosophila Embryonic Morphogenesis

α-Catenin is a core component of the cadherin-catenin adhesion complex that couples cadherin to the actin cytoskeleton. The mechanosensitive α-Catenin M region is thought to recruit F-actin binding partners such as Vinculin under application of force to support adherens junctions (AJs). However, the function of M region mechanosensing and its cooperation with binding partners to support dynamic adhesion in vivo remains unclear. Actomyosin contraction stretches the M region into an open conformation, revealing cryptic binding sites and recruiting Vinculin. Whereas the loss of α-Catenin compromises adhesion and morphogenesis, null mutants for the α-Catenin-binding partners Vinculin, α-Actinin and Ajuba complete embryogenesis with no or minimal defects. Furthermore, the contribution of the M region to recruitment of the only reported binding partner with any strong adhesion phenotype, Afadin/Canoe, has not been explored in vivo. Here we report an essential requirement for the M region to epithelial integrity during Drosophila morphogenesis. We determine the distinct contributions of the M region subdomains, M1, M2 and M3, with M2 making the major contribution to adhesion. M2 is required for the mechanosensitive enrichment of Ajuba, and together with M3 supports Canoe recruitment to tricellular junctions and reinforces AJs. In contrast, M1 negatively regulates adhesion through its inhibition of Ajuba recruitment. M1 also recruits Vinculin, which supports E-cadherin and adhesion at high tension edges. However, we find this role to be subtle - ultimately dispensable for adhesion. We also found that the M1-Vinculin interaction is redundant with Canoe, and a striking genetic interaction between the M region and Canoe, together suggesting that Canoe and the M region act in parallel to support AJs. Our data clarify the function of the cadherin-actin interface and argue that α-Catenin and its interaction partners are part of a cooperative and redundant network that supports AJs remodelling in embryogenesis.

Keywords: cadherin-catenin
cell adhesion
mechanosensing
Advisor: Tepass, Ulrich
In the Margins of Justice: The Negotiation of Social Values in Athenian Forensic Oratory

This dissertation is a study of four seminal value-terms in Athenian forensic oratory: philanthrōpia (generosity), epieikeia (decency), suggnōmē (pardon), and eusebeia (piety). Each chapter examines a different value-term, offers a theory of how that term works in Athenian forensic oratory, and then explores the political, social, and juridical consequences of the theory. Chapter One argues that philanthrōpia is not a disinterested “love of man,” but a particular type of generosity that implies a power-relation; as such, it was fought over by aristocrats and democrats alike, since it had the potential to signify both the noblesse oblige of the elite and the idealized goodwill of Athenian democracy. Chapter Two presents epieikeia as a flexible counter-value that can be put to diametrically-opposed ends: in the hands of Demosthenes, it is a baseline democratic “decency” attainable by all, while for Isocrates, it is an aristocratic excellence of education to which only the elite can aspire. Chapter Three makes the case for understanding suggnōmē as pardon based on a strong sense of cognitive and affective identification; as emblematic of the larger role of identification in the Athenian courtroom, suggnōmē was both constantly appealed to by the orators as well as periodically disowned. Finally, Chapter Four argues that eusebeia is a will-to-memory that, while seeming to recall the content of the dikastic oath, in fact acts as a floating signifier that the orators use to bolster that other floating signifier of the Athenian dikastērion: dikē. It is shown throughout that the study of these value-terms gives us insight not only into the terms themselves, but also into the larger political, social, juridical thought-worlds of Athens.

Keywords: Athens
democracy
law
oratory
rhetoric
values
Advisor: Wohl, Victoria
Modern Applications of Nickel Catalysis Towards the Synthesis of Nitriles and Related Compounds

This thesis describes the use of nickel catalysis and how it enables cross-coupling reactions with the goal of synthesizing α-aryl nitriles and related compounds. These strategies represent novel approaches to current limitations in the field and may be of interest to practitioners in the area. Chapter 1 describes an overview of the role nickel has in the modern landscape of transition metal catalysis, and the relevance/importance of nitrile containing organic molecules. Chapter 2 details a nucleophilic cyanation reaction of benzylic and allylic pivalate esters, and our initial efforts towards synthesizing enantioenriched α-aryl nitriles. Chapter 3 describes the use of α-cyano substituted NHP esters as electrophiles in a reductive arylation reaction, the unique role a chlorosilane additive has in the chemistry, and our continued efforts of generating enantioenriched products. Chapter 4 outlines the use of α-amide substituted NHP esters in a reductive arylation reaction to synthesize challenging 2° α-arylated amide products. Chapter 5 outlines some miscellaneous chemistry that relates to previous chapters

Keywords: Catalysis
Cross-Coupling
Nickel
Nitriles
Organic Chemistry
Synthetic
Advisor: Rousseaux, Sophie A. L.
Theranostic Implications of Molecular Imaging in Cancer

Molecular imaging (MI) agents use biomarker-targeted delivery vehicles complexed to radionuclides that emit gamma (γ)-photons or positrons for visualizing tumours by SPECT or PET, respectively. These MI agents can be functionalized with radionuclides that emit cytotoxic radiation such as beta (β) particles and structurally modified for radioimmunotherapy (RIT), effectively transforming into a theranostic agent. This thesis aimed to develop a MI agent to visualize tumours that overexpress the biomarkers of interest and demonstrate the feasibility of a theranostic approach against these tumours. Epidermal growth factor receptors (EGFR) are overexpressed in triple-negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDCa). Panitumumab is an antibody that targets EGFR and can be modified and functionalized for MI and RIT. The first study demonstrated a novel technique to conjugate synthetic His6-peptides to panitumumab Fab for complexing [99mTc(H2O)3(CO)3]+, rendering it the ability to visualize EGFR-positive cell-line or patient-derived tumour xenografts in mouse models of TNBC, HNSCC and PDCa. The next study showed the synthesis of the theranostic agent, DOTA-panitumumab F(ab')2, that can be complexed with 64-copper (64Cu) for PET imaging or 177-lutetium (177Lu) for RIT. This work showed that 64Cu-DOTA-panitumumab F(ab')2 imaged EGFR-positive HNSCC PDX mouse models on PET and importantly, allowed for prediction of radiation doses to normal organs and tumours from RIT with the 177Lu-labelled analogue, demonstrating a theranostic strategy towards HNSCC. The third study was an attempt to visualize PDCa tumours overexpressing FZD#5 in mouse models using a recombinant anti-FZD#5 Fab that harbored an endogenous His6-tag for complexing [99mTc(H2O)3(CO)3] + or an immunoglobulin (IgG) analogue modified with desferrioxamine (DFO) for labelling with 89-zirconium (89Zr). Overexpression of FZD#5 in PDCa is mediated by RNF-43 mutation and has shown tremendous therapeutic potential in recent studies. This work showed an insufficient density of FZD#5 for imaging PDCa with the 99mTc-labelled Fab on SPECT and non-specific uptake of the 89Zr-labelled IgG on PET due to enhanced permeation and retention effects. In conclusion, panitumumab can be functionalized as a MI agent or a theranostic agent for visualizing and treating EGFR-positive tumours. FZD#5 is not a viable biomarker for MI despite its therapeutic potential.

Keywords: Molecular Imaging
Radiation Oncology
Radioimmunotherapy
Theranostic
Advisor: Reilly, Raymond
Policy Learning in Global City-networks: Cycling Policy in Moscow, Russia as a Case of Local Global-urbanism

Flows of people and information connect cities around the world and enable mobility of policy ideas. In this thesis I explore local impacts of global circulation of urban policy ideas, focusing on policies that aim to promote cycling as a transport mode. Building on policy mobilities theories, I begin to conceptualize a new phenomenon, ‘local global-urbanism’, which describes local policy discourses, policies or projects that policy actors develop based on ideas from other contexts. As an empirical case of local global-urbanism I investigate the emergence of a cycling policy in Moscow, Russia, in the mid-2000s - 2016. Moscow and many other post-Socialist cities are characterized by legacies of centralized planning, recent and strong automobility cultures, and limited cycling planning experience. While literature on cycling policies in European post-Socialist cities is growing, less is known about such cities outside the European Union. The Moscow case study combines elements of policy mobilities theories, policy transfer analytical framework, and policy ethnography methodology. With this case study I address two research questions of this thesis: How do policy mobility theories help to understand the emergence of Moscow’s cycling policy? How does the case of Moscow’s cycling policy contribute to policy mobility scholarship? To answer these questions I explore motivations, policy actors, contents, trajectories, mechanisms, constraints and outcomes of policy learning and transfer. The Moscow case demonstrates that policy ideas and examples from the Global North and the Global South have informed the emerging cycling policy. Policy learning and transfer of ideas from other contexts can save time and resources, leverage cyclists’ advocacy efforts, legitimize policy decisions, and facilitate the development of cycling plans and policies and pilot testing cycling infrastructure. However, policy learning and transfer cannot guarantee the implementation of safe cycling infrastructure, alleviation of power imbalances, continued cooperation between decision-makers and the cycling community, and other aspects of policy-making dependent on local institutions and culture. This thesis contributes to transport policy and geography literature by introducing the concept of local global-urbanism, focusing on policy transfer in post-Socialist cities outside the EU, and analyzing Moscow's cycling policy as a case of local global-urbanism.

Keywords: cycling policy
policy mobilities
policy transfer
post-Socialist countries
Advisor: Hess, Paul M.
The Social and Cultural Framework of the Syriac Exegete’s World: The Influence of Rabbinic and Other Judaic Traditions

Early Syriac Christian commentaries on the problematic child sacrifice narratives of Scripture (Genesis 22; Judges 11; 2 Kings 3) contain ideas that are also present in Second Temple and late antique Jewish writings. This study aims to explore the extent to which the Jewish exegetical tradition, as codified in early Jewish and rabbinical writings, served as the foundation for several Syriac Christian commentaries on the biblical theme of child sacrifice. To test this hypothesis that the Christian authors were acquainted with Jewish exegetical materials and incorporated elements of it within their own commentaries, the contents and the stylistic features of works by Ephrem the Syrian, Jacob of Serugh and an anonymous fifth-century Syriac author on the relevant stories are analyzed against early Jewish and contemporaneous rabbinic materials to determine the degree of dependence. With regards Genesis 22 and 2 Kings 3, the number of parallels that exist between the texts in addition to the degree of similarity in the respective details, indicate that the Syriac authors must have had access to traditions that were circulating in Jewish learning circles. In the case of Judges 11, however, the Syriac commentaries differ drastically from details contained in Jewish works. The nature of the discrepancy is such that it indicates that Syriac authors were well-acquainted with Jewish traditions on the topic but opted for an interpretation that better suited their own theological outlook. The results of this study suggest that the Jewish and Christian worlds of late antique Syria were not as insular as previously thought. The works of the Christian authors indicate that they viewed the Jewish communities as being inheritors and possessors of genuine extrabiblical teachings for all things related to the Hebrew Bible. As adherents of a movement which stemmed out of the synagogue and claimed to supersede it, they felt an inherent right to borrow as they saw fitting. It was, fundamentally, an act through which the Syriac Christian author could reinforce his own and his movement’s identity and place in a Semitic-speaking geographical locale separated by two similar – yet distinct – religious traditions.

Keywords: Bible
Fathers
Interpretation
Rabbinics
Sacrifice
Syriac
Advisor: Harrak, Amir
A 3-dimensional in vitro Invasion Model to Study Breast Cancer Metastasis

Metastasis is a multi-step process that begins with cells invading into the stromal matrix. This process is rate-limiting as the components of the stromal matrix act as natural barriers. Therefore, it is important to study this process to understand the gene expression differences that allow certain cells to successfully disseminate. Currently, the community lacks an in vitro method that can both accurately recapitulate the tumour microenvironment and also allow subpopulation isolation to study gene expression differences. Digital microfluidics (DMF) is an emerging fluid-handing paradigm wherein discrete droplets (from picolitre to microlitre-sized) are manipulated on arrays of electrodes coated with hydrophobic insulators. Importantly, the reconfigurable set-up of DMF devices allows easy access to the contents of droplets used in the experiment and provides opportunities for detailed analysis. This thesis describes the development and validation of a novel functional invasion assay on DMF called CIMMS (cell invasion in digital microfluidic microgel systems) that can generate an array of complex microgels formed from multiple constituents and controllable geometries to mimic the microenvironment of early stages in metastatic dissemination. CIMMS was validated by characterizing the invasion profile of MDA-MB-231 cells under different seeding and matrix conditions. Most importantly, a microgel dissection technique was developed to allow for the extraction of subpopulations of invaded and non-invaded cells for RNA sequencing. This study revealed the subtle gene expression differences that related to the invasive phenotype, providing insight into which cells are most likely to take the first steps of metastasis. CIMMS was then applied to study the functional importance of the aryl hydrocarbon receptor (AHR) in breast cancer invasion. It was observed that AHR knockout in MDA-MB-231 cells shows enhanced invasiveness by upregulating matrix remodeling mechanisms, which agrees with reports indicating high AHR expression in cancer patients correlate with good prognosis. Overall, we propose that CIMMS is a useful new tool which combines functional analysis with RNA sequencing of subpopulations to study the biology of invasion-related pathologies.

Advisor: Wheeler, Aaron R
Anesthetic Activation of GABAA Receptors in Astrocytes Triggers a Persistent Increase in the Function of GABAA Receptors in Neurons via IL-1β and p38 MAPK-dependent Pathways

Introduction: Many patients develop perioperative neurocognitive disorders; however, the mechanisms underlying these disorders are poorly understood. Preclinical studies have shown that a brief exposure to a general anesthetic drug can trigger a persistent increase in inhibitory tonic current generated by α5GABAARs in hippocampal neurons. This increase in inhibitory current is associated with sustained postanesthetic cognitive deficits. Astrocytes, which are necessary for this effect, express anesthetic-sensitive GABAARs. However, it is unknown how anesthetic drugs act on astrocytes to trigger the persistent increase in tonic current. Astrocytes release IL-1β, which increases the tonic current in neurons via p38 MAPK-dependent pathways. However, it is also unknown if IL-1β can trigger a persistent change in neuronal GABAAR function via p38 MAPK following anesthetic treatment. Here, we test the hypothesis that anesthetic drugs activate GABAARs in astrocytes, which in turn increases cell-surface expression and function of α5GABAARs in neurons via IL-1β and p38 MAPK-dependent pathways.Methods: Astrocytes and neurons from mice were studied in ex vivo brain slices and in primary cell cultures. Patch clamp and biotinylation studies were used to study the role of GABAAR expressed in astrocytes in the response to anesthetic drugs. The expression profiles of GABAAR subtypes in astrocytes and neurons were studied with ddPCR and Western blotting. The release of IL-1β from astrocytes was evaluated with ELISA and mass spectrometry. IL-1β and p38 MAPK-dependent pathways were evaluated via whole-cell patch clamp recording and Western blot. Results: Inhibiting GABAARs in astrocytes prevented the anesthetic-induced increase in cell-surface expression and function of GABAAR in neurons. Astrocytes express a unique compliment of anesthetic-sensitive GABAARs. The increase of tonic current in neurons was dependent on IL-1β and p38 MAPK function. Conclusions: These results suggest that anesthetic drugs activate GABAARs in astrocytes, which in turn triggers IL-1β and p38 MAPK signaling pathways in neurons. This signaling cascade then causes a persistent increase in α5GABAAR cell-surface expression and function. These results identify a novel crosstalk mechanism between astrocytic GABAARs and neuronal GABAARs that may be targeted to mitigate postanesthetic neurocognitive deficits.

Keywords: Anaesthesia
Astrocytes
Biochemistry
Electrophysiology
GABA
Advisor: Orser, Beverley A
Pulsed Power Circuit Topologies for Gas Laser Applications

Gas lasers are a special class of lasers which generate laser pulses from the excitation of lasing species molecules by energetic free electrons within a gas mixture. The free electrons are created as a result of a plasma discharge. The emission spectrum of these lasers typically lies in the UV, visible and infrared regions and have a wide range of industrial, medical and research applications. Most gas lasers operate in pulsed mode and thus require a repetitive generation of high voltages over a short time period in order to initiate the discharge. This thesis focusses on improvements to the pulsed power circuit so as to achieve higher end-to-end efficiency, use less magnetic material and increase electrode lifetime. A novel integrated capacitor and snubber assembly that leads to a reduction in electrode erosion is proposed, designed and experimentally verified. The assembly’s coaxial design is shown to improve the energy dissipation by the snubber. Thus, the total amount of charge flowing through the main gap discharge in the post-lasing (late currents) stage is reduced by approximately 40%. Second, two new pulsed power topologies which use solid state switches instead of thyratron are proposed. The main drawback of solid state based pulsed power topologies is that they require a pulse transformer and pulse compression stages to avoid the use of a large number of series and paralleled switches that must be otherwise rated for 10’s of kVs and several kAs. The first circuit topology referred to as the ‘hybrid circuit topology’ accelerates the energy transfer time across the transformer. This reduces the total gain G_t required from the pulse compression stages by 25-35%. Thus a much lower volume (Vol∝G_t^2) of magnetic material is therefore required for the pulse compression circuits in order to meet this reduced gain requirement. The second proposed circuit topology referred to as the ‘transformerless circuit topology’ uses optimized capacitor sizes for producing a voltage gain in a cascaded resonant CLC circuit arrangement to eliminate the need for a pulse transformer. Lastly, the thesis proposes a new concept for achieving a high (>60kV) ignition voltage. Achieving a high ignition voltage requires charging the peaking capacitors in a shorter period of time (few 10’s of nanoseconds). The lowest achievable limit on the charging time is constrained by the stray loop inductance in the pulsed power circuit. The thesis introduces a new concept in order to achieve shorter voltage rise-times across the main gap. The new concept can be applied to both short pulse and long pulse lasers.

Advisor: Dawson, Francis