VictorJuiz/thesis huggingface dataset:
Maria Mediatrix: Mediating the Divine in the Devotional Literature of Late Medieval England

Christianity, as a religion centered on the Incarnation of a spiritual being, is always necessarily a religion of embodiment, but its attitude toward that embodiment has always been one of distrust. The juxtaposition of seemingly opposing forces—flesh and spirit, affect and intellect—results in problematic but inevitable troubling of binary oppositions. Late medieval devotion is replete with mediators that serve to focus meditation and prayer in order to bring the individual closer to God, but they can also represent the physical presence of God and bring God closer to the individual. A study of these various modes of mediation will reveal how the connections between spiritual and physical were conceived. Mediation—whether of language, the senses and emotions, texts and objects, or saints—reveals and reestablishes our connection to the divine. Using the depictions of the Virgin Mary, the Mediatrix, found in the devotional literature of medieval England as a starting point, this study explores the mechanism of mediation in medieval Christian thought. The first two chapters examine the problem of the erotic in religious discourse, focusing primarily on architectural allegory and imagery and language borrowed from the Song of Songs. Architectural allegories representing the female body of the Virgin Mary and the female religious draw on both spiritual allegories and allegories found in secular love poetry and romance. The use of eros in devotional discourse creates a tension between the prescribed chastity and sensory restriction and the highly sensual, sexual language and heightens the emotional effect of the text. The second two chapters focus on compassion, first looking at planctus Mariae, or Marian laments, to examine how a meditating reader is drawn into the scene of the passion through dialogue with Mary and through Mary’s control of the meditative gaze. The final chapter examines how devotional images can be used as mediators because of their ability to represent (and in some sense be) an invisible, divine reality.

Keywords: Medieval English Literature
Advisor: Akbari, Suzanne Conklin
Eurasian Snow Cover and the Role of Linear Interference in Stratosphere-troposphere Interactions

The classical problem of predicting the atmospheric circulation response to extratropical surface forcing is revisited in the context of the observed connection between autumn snow cover anomalies over Eurasia and the wintertime Northern Annular Mode (NAM). In general circulation model (GCM) simulations with prescribed autumn Siberian snow forcing, a vertically propagating Rossby wave train is generated, driving dynamical stratospheric warming and a negative NAM response that couples to the troposphere. It is shown that unexplained aspects of the evolution of this response can be clarified by examining the time evolution of the phasing, and hence the linear interference, between the wave response and the background climatological wave. When the wave response and background wave are in phase (out of phase), wave activity into the stratosphere is amplified (attenuated) and the zonal mean stratosphere-troposphere NAM response displays a negative (positive) tendency. This effect is probed further in a simplified GCM with imposed lower tropospheric cooling. As in the comprehensive GCM, linear interference strongly influences the NAM response. The transition from linear to nonlinear behaviour is shown to depend on forcing strength. Linear interference also plays a key role in the observed October Eurasian snow cover-NAM connection. It is shown that the time lag between October Eurasian snow anomalies and the peak wave activity flux arises because the Rossby wave train associated with the snow is out of phase with the climatological stationary wave from October to mid-November. Beginning in mid-November, the associated wave anomaly migrates into phase with the climatological wave, leading to constructive interference and anomalously positive upward wave activity fluxes. Current generation climate models do not capture this behaviour. Linear interference is not only associated with stratospheric warming due to Eurasian snow cover anomalies but is a general feature of both Northern and Southern Hemisphere stratosphere-troposphere interactions, and in particular dominated the negative NAM events of the fall-winter of 2009-2010. The interannual variability in upward wave activity flux during the season of strongest stratosphere-troposphere interactions is primarily determined by linear interference of quasi-stationary waves. The persistence of the linear interference component of this flux may help improve wintertime extratropical predictability.

Keywords: Northern Annular Mode
Eurasian snow
Stratosphere-troposphere coupling
Linear interference
Advisor: Kushner, Paul
Detection of Perfectly-conducting Targets with Airborne Electromagnetic Systems

A significant problem with exploring for electrically conductive mineral deposits with airborne electromagnetic (AEM) methods is that many of the most valuable sulphide deposits are too conductive to be detected with conventional systems. High-grade sulphide deposits with bulk electrical conductivities on the order of 100,000 S/m can appear as “perfect conductors” to most EM systems because the decay of secondary fields (the “time constant” of the deposit) generated in the target by the system transmitter takes much longer than the short measuring time of EM systems. Their EM response is essentially undetectable with off-time measurements. One solution is to make measurements during the transmitter on-time when the secondary field of the target produced by magnetic flux exclusion is large. The difficulty is that the secondary field must be measured in the presence of a primary field which is orders of magnitude larger. The goal of this thesis is to advance the methodology of making AEM measurements during transmitter on-time by analysing experimental data from three different AEM systems. The first system analysed is a very large separation, two helicopter system where geometry is measured using GPS sensors. In order to calculate the primary field at the receiver with sufficient accuracy, the very large (nominally 400 m) separation requires geometry to be known to better than 1 m. Using the measured geometry to estimate and remove the primary field, I show that a very conductive target can be detected at depths of 200m using the total secondary field. I then used fluxgate magnetometers to correct for receiver rotation which allowed the component of the secondary field to be determined. The second system I examined was a large separation fixed-wing AEM system. Using a towed receiver bird with a smaller (˜ 135m) separation, the geometry must be known much more accurately. In the absence of direct measurement of this geometry, I used a least-squares prediction approach using measurements of aircraft manoeuvres which allowed primary field contamination to be estimated. Subtracting this estimate from the recorded signal increased the maximum time constant observed in a field survey for conductive targets by a factor of seven. Finally, a study of a nominally rigid helicopter EM system employing a bucking coil to cancel primary field showed that system geometry (specifically, the position of the receiver coil relative to the transmitter and bucking coils) must be known to better than 0.01 mm to detect deep targets. Again, direct measurements of system geometry were not available. A least-squares prediction filter using helicopter manoeuvre and system pitch and roll measurements was applied, but was not able to estimate primary field well enough to provide an accurate secondary on-time response. Direct measurements of relative motion of the system components might solve this problem.

Keywords: airborne
electromagnetic
geophysics
exploration
on-time
inductive limit
Advisor: Bailey, Richard
The Roles of Hsp90 and Calcineurin in Antifungal Drug Resistance

Candida species are the fourth most common cause of hospital-acquired blood-stream infections in the United States with mortality rates approaching 50%. Treatment of candidiasis is hampered by the limited number of antifungal drugs whose efficacy is compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. I established a new role for the essential molecular chaperone Hsp90 and the protein phosphatase calcineurin in regulating resistance to cell wall stress exerted by the echinocandins, the only new class of antifungal drug to reach the clinic in decades, in both Candida albicans and Candida glabrata, the two leading causes of candidiasis. Through reciprocal co-immunoprecipitation studies, calcineurin activation studies, and protein stability assays, I established calcineurin as the first client protein of Hsp90 in C. albicans. I found that the calcineurin downstream effector Crz1 plays only a partial role in mediating tolerance to the echinocandins in C. albicans, implicating additional downstream effectors. Complementary studies in the model organism Saccharomyces cerevisiae revealed a divergence in the requirement of Hsp90 and calcineurin in this species’ ability to tolerate echinocandins despite a conserved functional relationship ii between Hsp90 and calcineurin. I also provided the first global view of mutations that accompany the evolution of fungal drug resistance in a human host. I found an association of mutations in CDC6 and MOH1 with echinocandin resistance in unrelated C. glabrata clinical isolates, genes previously not implicated in echinocandin resistance. I propose a new model by which Hsp90 and calcineurin regulate echinocandin resistance by controlling expression of the resistance determinant FKS2. Taken together, my research reveals new mechanisms mediating antifungal drug resistance and suggests new therapeutic strategies to save human lives.

Keywords: Microbiology
Advisor: Cowen, Leah
The Design and Testing of a Less Invasive Dual Plate System for Posterior Spinal Fusion

Spinal fusion is the process by which two or more vertebral levels are joined into a single, solid bone mass in order to restore stability to a spine that has been compromised by trauma, degeneracy or metastasis. Fusion is accomplished through internal hardware positioned anteriorly, posteriorly, or with combined anterior-posterior instrumentation. Since the 1990s the frequency of spinal fusions has been rising, and this trend is expected to continue. Posterior approaches to fusion are most common, primarily consisting of pedicle screw and rod constructs. Despite the high success rate for bony fusion with pedicle screw fixation, this technique poses risks to delicate neurological and vascular structures and is heavily dependent on surgeon expertise. In this thesis, a novel and less invasive posterior spinal hardware system was designed and evaluated, which solely utilizes the spinous processes and laminae of the vertebrae as the point of the bone-implant interface. Morphological and biomechanical studies of the posterior spine were undertaken in order to define important geometric information to guide the design of the proposed hardware and to determine the strength of the posterior elements throughout the spine to assess their ability to support posterior element plating. Utilizing this information, a modular dual plate fusion system was developed for single or multi-level fusion. The system accounts for the native curvature of the spine and can be extended to additional vertebral levels at the time of insertion, or at any later time. Prototypes were manufactured in titanium. Positive biomechanical results were found when the proposed hardware was used as a supplement to anterior instrumentation. Additionally, work focused on 2D-3D registration of neutral CT data with flexion extension x-ray images, was undertaken and shown to yield improved accuracy of important vertebral metrics utilized for clinical assessment of spine stability. This technique is applicable to the evaluation of pathology and kinematics at any level of the spine, including post-fusion adjacent level degeneration. The culmination of this work has resulted in a novel, patent pending posterior element spinal fusion system.

Keywords: Spinal Fusion
Spine
medical devices
design
testing
Advisor: Whyne, Cari
Ginsberg, Howard
Investigating the Effects of Early and Current Thyroid Hormone Status on Higher-order Visual Abilities

Congenital hypothyroidism (CH), a pediatric endocrine condition that results in early thyroid hormone (TH) insufficiency, is associated with visuospatial dysfunction suggestive of selective dorsal visual stream impairment. However, the ventral visual stream has not been adequately investigated in this population and so the effect of early TH insufficiency on development of the two streams had not been clearly established. This thesis used a comprehensive set of neuropsychological and experimental tests to assess higher-order visual functions in children and adolescents with CH compared with typically developing individuals. The results show that while CH is associated with poorer performance on tasks tapping into dorsal stream functions such as judgment of line orientation, spatial localization, three-dimensional block and two-dimensional mental construction, judgment of object location, and mental rotation, performance on typical ventral stream tasks such as identity discrimination, including abstract shapes, faces, and buildings, is relatively unimpaired. Thus this thesis establishes that the dorsal visual stream is selectively vulnerable to TH insufficiency. In addition to the investigating the nature of the higher-order visual problems in CH, this thesis explores the mechanism underlying these problems and assesses whether they result from organizational effects by early TH or activational effects by current TH levels. The data support the organizational mechanism and suggest that prenatal TH insufficiency results in irreversible changes to the dorsal visual stream due to the timing of dorsal stream development, which occurs earlier than ventral stream development and is thus more vulnerable to insult.

Keywords: thyroid hormone
dorsal stream vulnerability
Advisor: Rovet, Joanne
The Things That Move and Bind Us: The Roles of Kinesin in Membrane and Receptor Trafficking

Pseudopod formation during phagocytosis is a limiting step in managing the uptake of particles and here we show that the conventional kinesin is involved in both receptor and membrane delivery to the phagocytic cup. Expression of a mutant kinesin isoform (EGFP-Kif5B-DN) in RAW264.7 cells significantly reduced binding of IgG-sRBCs when macrophages were faced with multiple encounters with opsonized particles. SEM analysis of EGFP-Kif5B-DN expressing cells showed sparse, extremely thin pseudopods. We saw disrupted Rab11 trafficking to the phagocytic cup in EGFP-Kif5B-DN-transfected cells. Our opsonized particle overload assays also implicated phagosome membrane recycling in pseudopod formation. We observed reduced phagosome fission and trafficking in mutant kinesin expressing cells as well as reduced cell surface expression of Fcy and Mac-1 receptors. It is evident that anterograde trafficking via kinesin is essential both for receptor recycling from the phagosome as well as delivery of Rab11-containing membrane stores to effect broad and functional pseudopods. We noticed an actin cup defect in EGFP-Kif5B-DN-transfected cells and turned to focal adhesions to investigate the role of kinesin in actin assembly at the membrane. To investigate the role for kinesin in focal adhesion formation we examined nascent focal adhesions formation in CHO-ΙΙA cells. Transfected, EGFP-Kif5B-DN transfected cells were less spread compared to control cells and displayed a “halo” pattern of focal adhesions at the base of the cell. To see if this was a defect in upstream receptors involved in focal adhesion assembly we investigated surface integrin levels in EGFP-Kif5B-DN transfected cells. Using flow cytometry and immunofluorescence analysis we observed decreased levels of β1-integrin at the surface of EGFP-Kif5B-DN transfected cells, compared to control cells. We investigated the signaling requirements for kinesin-mediated integrin transport and determined that β1-integrin transport from the recycling compartment is regulated by the PI(3)K-PKB/AKT-GSK-3β pathway. Thus in the absence of functional kinesin, cells fail to form proper focal adhesion sites due to lack of adhesion and substrate contact resulting in the loss of cell spreading.

Keywords: Phagocytosis
Microtubules
Advisor: Harrison, Rene E.
Growth of Planetesimals and the Formation of Debris Disks

At the edge of the Solar System lies the Kuiper Belt, a ring of leftover planetesimals from the era of planet formation. Collisions between the Kuiper Belt Objects produce dust grains, which absorb and re-radiate stellar radiation. The total amount of stellar radiation so absorbed is perhaps one part in ten million. Analogous to this, Sun-like stars at Sun-like ages commonly have dusty debris disks, which absorb and re-radiate as much as one part in ten thousand of the stellar radiation. We set out to understand this difference. In chapter 1, we outline the relevant observations and give a feel for the relevant physics. In chapter 2, we turn to the extrasolar debris disks. Using disks spanning a wide range of ages, we construct a pseudo-evolution sequence for extrasolar debris disks. We apply a straightforward collision model to this sequence, and find that the brightest disks are a hundred to a thousand times as massive as the Kuiper Belt, which causes the difference in dust luminosity. Current theoretical models of planetesimal growth predict very low efficiency in making large planetesimals, such that the Kuiper Belt should be the typical outcome of Minimum Mass Solar Nebula type disks. These models cannot produce the massive disks we find around other stars. We revisit these models in chapter 3, to understand the origin of this low efficiency. We confirm that these models, which begin with kilometer sized planetesimals, cannot produce the observed extrasolar debris disks. Instead, we propose an alternate model where most mass begins in centimeter sized grains, with some kilometer sized seed planetesimals. In this model, collisional cooling amongst the centimeter grains produces a new growth mode. We show in chapter 4 that this can produce the Kuiper Belt from a belt not much more massive than the Kuiper Belt today. We follow in chapter 5 by showing that this model can also produce the massive planetesimal populations needed to produce extrasolar debris disks.

Keywords: Planet Formation
Debris Disks
Astronomy
Astrophysics
Advisor: Wu, Yanqin
Targeting Plasmodium falciparum Heat Shock Protein 90 (PfHsp90): A Strategy to Reverse Antimalarial Resistance

Drug resistance is one of the major impediments to control Plasmodium falciparum malaria worldwide. Heat shock protein 90 (Hsp90) is an essential component of the buffering capacity of eukaryotic cells as a part of the stress response. P. falciparum is no different and requires Hsp90 to chaperone proteins essential for cell cycle progression and drug resistance. Inhibition of P. falciparum Hsp90 (PfHsp90) may be able to not only cripple the parasite but also serve as an adjunctive antimalarial by circumventing drug resistance. The results presented in this thesis identify novel Hsp90 inhibitors that synergize with conventional antimicrobials, such as chloroquine (CQ), when used in combination. The objectives were to identify specific malaria Hsp90 inhibitors, the mechanism of the synergistic phenotype, and whether the strategy translates in vivo. To this end, the antimalarial activity of the purine analog PU-H71, and novel PfHsp90 inhibitors was tested. PU-H71 and the novel inhibitors APPA, harmine, and acrisorcin exhibited antimalarial activity in the nanomolar range and displayed synergistic activity with CQ. PU-H71 was able to reverse CQ resistance in a cell-based assay using the CQ-resistant strain W2. PU-H71 caused ring-stage arrest during the intra-erythrocytic cycle. Co-immunoprecipitation studies revealed that PfHsp90 interacts directly with the CQ resistance transporter (PfCRT). In the P. berghei mouse model of malaria, PU-H71 and harmine were able to reduce parasitemia and synergize with CQ. The interaction of PfHsp90 with PfCRT may underlie the synergistic phenotype. We conclude that PU-H71 and harmine are effective adjunctive antimalarial drugs that may be useful in combination therapies.

Keywords: malaria
hsp90
Advisor: Pillai, Dylan Ravindran
Low, Donald E.
Learning to Transition: Nurses' Entry into Cancer Nursing Practice

In the 21st century, the delivery of cancer care is facing unprecedented challenges, including an increasing number of cancer patients, a shortage of nursing personnel, a shift in care from in-patient to outpatient facilities, and new technologies requiring additional resources and education. The purpose of this critical qualitative study was to explore how nurses learn to transition into cancer nursing practice (CNP) in the workplace. The inquiry examined the contextual and learning factors that enhanced or impeded the nurses’ transition into diverse cancer settings. A comprehensive literature review was conducted in three areas: workplace identity and transitions; social learning theories and informal learning in nursing practice; and the context of cancerland, namely, cancer system, cancer patients’ experience, and cancer nursing as a specialty. Participants completed a preinterview questionnaire that determined whether they met the criteria and were representative of the phenomenon being studied. Telephone interviews were conducted with 15 nurses with more than 3 months and less than 2 years working in 1 of 4 cancer facilities in Ontario. An interpretive, phenomenological approach was used to formulate a description of the newly hired nurses’ lived experience. Three overarching themes emerged unique to CNP: (a) Getting In - nurses perceptions of their recruitment and selection into CNP; (b) Surviving In - nurses’ struggles learning CNP and the emotional strain of “being with” critically ill and dying patients; and (c) Staying In - factors that impacted the nurses’ decision to stay or leave, such as effective nursing leadership, quality of work life, and accessibility of supports (preceptors and mentors) and professional education. The findings will assist nursing leaders, educators, and preceptors when developing strategies to enhance the recruitment, orientation, and education of nurses into CNP. The review included a description of the ways in which the nurses perceived their new role, as well as the rewards and difficulties they encountered as they coped during their first few months of practice. Also included were descriptions of the ways in which the nurses learned to transition into the different cancer nursing subspecialties of in-patient; outpatient; chemotherapy; radiation therapy; and urban, rural, and remote settings.

Keywords: oncology nursing
workplace transitions
cancer care
informal learning
Advisor: Bascia, Nina