VictorJuiz/thesis huggingface dataset:
A Role for Adult Born Neurons in Memory Processing
Keywords: adult neurogenesis
memory

Throughout adulthood, the brain continuously generates new neurons in two neurogenic regions: the subgranular zone of the hippocampus and the subventricular zone on the lateral wall of the lateral ventricles. These neurons have been shown to integrate into hippocampal and olfactory bulb circuitry, respectively. Nevertheless, their specific contribution to hippocampal or olfactory function remains unclear. Previous studies have tried to assess adult born neuron contribution to memory function by suppressing neurogenesis and examining the impact on memory acquisition. Although ablation of neurogenesis has been shown to impair performance in hippocampus dependent and olfactory tasks, many studies fail to see an effect. Compensation from residual cells in either system after ablation may underlie these contradictory findings. Thus, a more direct approach to answer this question would be to ablate adult born neurons after their incorporation into the memory trace. To do this, we established a double transgenic strategy to tag and selectively ablate adult born neurons with temporal control. Ablation of a population of predominantly mature, adult generated dentate granule cells did not prevent acquisition of contextual fear conditioning or Morris Water Maze memories. Removal of that same population of cells after training, however, led to memory degradation in three hippocampus dependent tasks. Similarly, post-training ablation of a population of adult generated olfactory interneurons iii impaired performance in an associative odour memory task, whereas pre-training ablation had no impact. Together, these data show that adult generated neurons form a crucial component of both hippocampal and olfactory memory traces.
Primus Theatre: Establishing an Alternative Model for Creating Theatre in English Canada
Keywords: devised theatre
performance

This study of Primus Theatre is evidence of many things. First and foremost it is a long overdue print recognition of Primus Theatre's substantial artistic accomplishments and its important contribution to the development of theatre-making in English-speaking Canada. In examining the various factors contributing to the founding of the theatre company and the extremely challenging conditions in which company members functioned over the years, it remains truly remarkable that Primus Theatre existed at all. Three central determinations emerge from the examination of Primus Theatre's practice. The theatre company truly was a pioneering venture in English Canada. Company members established an "as-if-permanent" ensemble that engaged in the creation of original performance work drawn from research that emerged from their regular training practice. The company adopted a theatre-making practice generated by the Odin Theatre in Denmark and then adapted it to vastly different cultural and fiscal contexts. It can also be determined that the origins of the company are inextricably bound to Artistic Director Richard Fowler's personal artistic journey. His strong sense of the creative and communal potential for theatre not only fuelled his own creative journey but also inspired National Theatre School students to launch their own acts of courage. The third determination arising from this study is that, while all aspects of Primus Theatre's creative practice can be linked to that of the Odin Theatre, this relationship can most accurately be described as an imprinting, rather than as an extension, of Odin Theatre practices. The conscious and unconscious permutation and advancement of the practice, driven by the technical and creative needs and interests of the young Canadian company and deeply affected by substantial financial hardships and creative set-backs, forced Primus to emerge as a unique theatrical entity developing from a particular and identifiable geneology. This study of the establishment of Primus Theatre also provides evidence that the substantial hardships faced by company members did not dissuade them from advancing their practice of continued exploration of form and expression. The study provides evidence not only of Primus Theatre's substantial body of creative work but also of its substantial pedagogical efforts. Subsequently, a new generation of theatre artists has been inspired by and trained in this alternative theatre-making model, and are making their own contributions to the continued redefinition of theatre in English Canada.
In-between Words: Late Modernist Style in the Novels of Henry Green, Ivy Compton-Burnett, Samuel Beckett, and Elizabeth Bowen
Keywords: Modernism
Late Modernism
Style
Repetition
Novel
Syntax
Omission
Doubt
Beckett, Samuel
Green, Henry
Compton-Burnett, Ivy
Bowen, Elizabeth
Dialogue

This dissertation seeks to identify, contextualize, and explain the achievement of late modernist novelists. Late modernism represents a significant, under-examined chapter in the development of the twentieth-century novel. Unlike the majority of their peers in the decades after modernism’s height, novelists such as Henry Green, Ivy Compton-Burnett, and Elizabeth Bowen—and the best-known, Samuel Beckett—continue to innovate in prose rather than returning to realism. Unlike their predecessors, late modernists move towards doubt, eschewing the sometimes ultimately redemptive ethos of high modernism. They do so without the insistence of later postmodernists, however, or their playful mood. The result is something new, strange, and “in between.” The aims of this study are to specify the nature of late modernist style, place it in its aesthetic and historical context, and explain its significance. Each chapter is a close reading of key works by one writer: each novelist uses different techniques to add to the late modernist aesthetic, but they all move in the same direction. The first chapter explores Henry Green’s work, analyzing the textual omissions and narrative construction that make his novels so evasive. In Compton-Burnett’s case, the focus is on how dialogue creates a constantly shifting moral world in which nothing can be taken for granted. The chapter on Beckett explores repetition, both as a microscopic stylistic tool and an organizing device that prevents the text from reaching conclusion. In examining Bowen, the centre is how her syntax circles continually around various kinds of “nothingness” and self-reflexively suggests ways to explore it. This study arranges late modernist novelists in a new continuum alongside Samuel Beckett, with the result that Beckett seems less a unique genius, and the other late modernist writers seem less eccentric and more profoundly challenging. They all seek ways to go on writing when doing so seems impossible. Late modernists bring something new to the novel. Through the smallest stylistic gestures, their works make and unmake themselves, refusing to allow the reader finality. They avoid the aesthetic and philosophical associations of either consolation or utter uncertainty; late modernists matter by refusing to matter in a familiar way.
Geography and Space in the Poetry of Prudentius
Keywords: Latin poetry
Prudentius

This dissertation examines the themes of geography and space in the poetry of the late antique Latin poet Prudentius (348-c.405 CE). The first chapter discusses the geography of reading, and suggests that Prudentius’ Peristephanon provides a means for the reader to experience the sites of the cults of the martyrs by reading about them rather than by having to travel to see them. It is also argued that the varying orders of the poems of the Peristephanon in the manuscript tradition can be explained by the differing interests of early readers, and that the arrangement extant in one group of manuscripts can be seen to be the result of organising the poems to fit a geographical itinerary. The second chapter investigates the intertextual aspect of literary journeys, and argues that late antique descriptions of journeys are as much indebted to the literary tradition as they are to “lived” experience on the part of the narrator. This chapter focuses in particular on Ausonius' Mosella, and the third, ninth, and eleventh hymns of Prudentius' Peristephanon. The third chapter discusses the representation of the city in the works of Prudentius, and shows how Prudentius’ approach to the civic nature of martyrdom in the Peristephanon must be related to the contemporary Christian perception that earthly civic obligations are not fundamentally incompatible with participation in the heavenly city of the afterlife. The fourth chapter examines the representation of pastoral spaces in the Liber Cathemerinon and the discussion of farming and religion in the Contra Orationem Symmachi. The final chapter addresses Prudentius' descriptions of works of art and architecture, particularly churches, and argues that Prudentius exhibits a marked preference for the word over the image as a means of conveying knowledge. A brief conclusion suggests that Prudentius’ representation of physical and imaginary spaces is always governed by a belief in the primacy of the written word, and by a fundamentally bookish approach to the world.
Design of a Microfluidic Based Lab-on-a-chip for Integrated Sample Manipulation and Dispensing
Keywords: Mechanical Engineering
Microfluidics
Microdroplet
Microarray
Electrowetting
Digital Microfluidics

Microfluidic based miniature lab-on-a-chip devices integrate different laboratory functionality in microscale. Microarray technology is evolving as a powerful tool for biomedical and pharmaceutical applications to identify gene sequences or to determine gene expression levels. Preparation of samples and spotting the arrays are the two major steps required for making microarrays. The microfluidic components developed in this research would facilitate performing the above-mentioned steps by a single lab-on-a-chip. Three microfluidic modules were developed: a non-contact microdispenser, an interface connecting the microdispenser with planar Electrowetting on Dielectric (EWOD) sample manipulator and a microvalve that controls the flow at the interface. An electrostatically actuated non-contact type drop-on-demand based microdispenser was developed. The dispenser was designed using finite element modeling technique that solved electrostatically actuated dispensing process. Prototypes were fabricated and tested verifying stable droplet dispensing with error in subsequent droplet generation was less than 15% between each droplet. The frequency of stable generation was 20 Hz and the average volume of dispensed droplet was 1 nL. A closed-channel EWOD actuated interface was developed that allowed a series of droplets to merge inside at the interface converting droplet flow to a continuous flow. An innovative design modification allowed series of droplet merging inside closed-channel. The interface allows integration of pressure driven devices such as: pumps, dispensers, and valves with droplet based planar EWOD devices. A novel EWOD based microvalve was developed that utilizes a thermo-responsive polymer to block and unblock a pressurized continuous flow. EWOD actuation was used to control the positioning of the valving polymer at location of interest. The valve also isolated a pressurized flow from an integrated planar EWOD device. Valves with zero leak rates were demonstrated. Such a valve will be useful in controlling microflows in EWOD to pressure driven flows such as dispensers.
Defining the Roles of Oncogenic Pik3ca Mutations and Genetic Cooperation in Mouse Models of Breast Cancer
Keywords: breast cancer
Pik3ca mutations

Most human breast tumors have mutations in the growth factor/phosphatidylinositol 3’ kinase (PI3K) pathway. These can occur in genes coding for receptors, adaptor proteins, catalytic and regulatory subunits of PI3K, downstream kinases, or antagonistic tumor suppressors. While each genetic change results in elevated PI3K signaling, and all major breast cancer subtypes show pathway activation, the specific mutations involved in any one tumor may play an important role in defining tumor subtype, prognosis and sensitivity to therapy. Here, I describe mouse models of PI3K-induced breast cancer. First I generated mice that express Pik3ca cDNA under control of the ROSA26 promoter, in a Cre-dependent and therefore tissue specific way. I have generated four strains of knock-in mice: R26-Pik3cawt, R26-Pik3caE545K, R26-Pik3caH1047R, and R26-Pik3caE545K-H1047R, which can be induced to express wild type, helical domain, kinase domain and double mutant forms of mouse p110α, respectively. Mice expressing mutant Pi3kca develop mammary tumors, but the phenotypic spectrum for each mutation is unique. Indeed, many E545K mammary tumors are ii vascularized, whereas H1047R tumors are not. Using these models, I have compared downstream signaling properties of E545K and H1047R. The potential for improved breast cancer treatment lies in combination therapies that target more than one oncogenic pathway. To develop such treatments, we need good mouse models, and an understanding of the oncogenic network. To this end, my Pik3caH1047R model was mated to p53 and PTEN knockout mice, and to mice with active Notch1 signaling. In each case, genetic cooperation was observed and characterized. Oncogenic PI3K cooperated with p53-loss and active Notch1 to decrease survival and alter tumor phenotype in distinct ways. Loss of PTEN cooperated with oncogenic PI3K to alter tumor type, decrease average age at end point, and increase the number of tumors per mouse. Overall, I have shown that Pik3caE545K and Pik3caH1047R are sufficient to induce mammary tumors, and that tumor characteristics differ with these mutations, and with cooperating genetic changes.
Molecular Mechanisms of Medulloblastoma Formation: Tumor Suppressor Functions of Hedgehog Pathway Components
Keywords: hedgehog
medulloblastoma

Hedgehog (Hh) signaling is essential for embryonic development and adult homeostasis. Aberrant pathway activity can result in various developmental disorders and cancers. The Hh receptor Patched1 (Ptc1) is a negative regulator of the pathway and acts as a tumor suppressor. Our lab and others have shown that Suppressor of fused (Su(fu)) and Kinesin family member 7 (Kif7) are major negative regulators of the pathway that function downstream of Ptc1. Medulloblastoma (MB) is the most common malignant pediatric brain tumor originating from the cerebellum. Several forms of MB have been identified, with abnormal activation of the Hh pathway associated with one major subtype. These tumors commonly show inactivating mutations in PTCH1, whereas mutations in SU(FU) are more rare. Mouse models with deletion of Ptc1 or expression of a constitutively active form of Smoothened (Smo) exhibit elevated Hh pathway activity, leading to MB formation. In this study, I examined the complex roles of Su(fu) in the formation of MB alongside the inactivation of Ptc1, Kif7 and p53 in the cerebellum. Unlike Ptc1+/- mice, Su(fu)+/- mice do not develop MB, even upon exposure to DNA damaging agents (X-ray irradiation or chemical carcinogenesis), which dramatically increases MB incidence in Ptc1+/- mutants. However, Su(fu)+/-;p53-/- mice develop MB and these MB tumor cells exhibit loss of heterozygosity of Su(fu), suggesting a protective role of p53 in tumor suppression in Su(fu) deficiency. Kif7+/- mice are not prone to tumorigenesis, even with deletion of p53. To bypass the embryonic lethality of Su(fu)- and Kif7-null mice, I generated neural stem cell-specific knockout mice, GFAP-Cre;Su(fu)f/f and GFAP-Cre;Kif7f/f. GFAP-Cre;Su(fu)f/f mice exhibit a severely disorganized cerebellum, with drastic up-regulation of p53 expression, and they survive past 1 year of age and do not develop MB. In contrast, GFAP-Cre;Kif7f/f mice appear grossly normal with only subtle cerebellar defects. These observations indicate that neither Su(fu) nor Kif7 inactivation is sufficient to drive tumorigenesis in the cerebellum. To investigate whether Su(fu) and Kif7 possess any overlapping tumor suppressor functions, I generated GFAP-Cre;Kif7f/f;Su(fu)f/f mice. Indeed, simultaneous loss of these negative regulators resulted in MB formation, which is correlated with increased Hh pathway activity as well as a lower level of p53 expression. Furthermore, I discovered a novel positive role for Su(fu) in MB development, as Su(fu) activity is required for robust formation of MB in Ptc1-deficient mice. Together, these data illustrate that Su(fu) plays a dual role in the genesis of MB, and suggest that the rare human MBs with SU(FU) mutations could be caused by simultaneous deletion of TP53 or KIF7.
The Stagehands of Subversive Spaces: Site-specific Performance and Audience Labour
Keywords: performance and place
theatre
audiences
site-specific performance
relational art
contemporary Canadian performance

This dissertation develops a theory for analyzing the role of audiences as aesthetic resources in contemporary site-specific performance and relational art. Collaborating with three Canadian companies as a participant-observer, interviewer, and in some cases, documenter, I develop case studies that track flexible stage-audience relationships in public spaces. By analyzing how companies Radix Theatre Society, Bluemouth, and Mammalian Diving Reflex put spectators to work in sites like IKEA showrooms, disused warehouses, and theatres, I advance a method that attends to the doubled practice of the spectator as worker and witness. This framework, which I term bifold spectatorship, articulates how audiences constitute theatrical worlds through direct physical engagement with the cultural criticism and formal experimentation that artists stage. Folded into the event, spectators literally compose the scene of the action, and enter into what I call critical proximity with the discourses that shape the performance. As participants interact with and directly query the artistic expressions that they patron, they answer a challenge to perform that is typically reserved for professionals. Such novel participation begins with a hail that interpellates audiences into the action as subjects and even sites of performance. Adapting the concept of the casting call, or what I coin site-casting, miscasting, and central casting, I show how spectators are aligned with the exigencies of the site; “mis-placed” or miscast by artists (provoking performance anxiety in participants); or cast to play a role they already perform in their everyday lives. In addition to these critical frameworks, I challenge the established narrative of “liberating the audience” by forwarding a multi-sited genealogy of site-specific performance that confronts the romance of freeing spectators from stage conventions. In examining the ethical problems that arise when audiences are made responsible for representation, The Stagehands of Subversive Spaces extends debates within site-specific performance to wider conversations in performance studies about ethics, subjectivity, and audience reception.
Understanding the Source of Emotions: Anxiety, Emotion Understanding Ability, and Risk-taking
Keywords: emotional intelligence
decision making

Can only a subset of individuals – those higher on the ability to understand the sources of emotions – determine whether to disregard or allow the effects of emotions when making decisions? I test two central predictions. First, I test whether individuals high on emotion understanding ability (EUA), one of the key dimensions of emotional intelligence, are less affected by incidental anxiety when making decisions involving risk than their lower ability counterparts. The rationale for this prediction is that individuals who have high EUA are able to correctly identify their source of anxiety and, based on perceived irrelevance, disregard incidental anxiety when making risky decisions, whereas individuals who have low EUA are confused about the source of anxiety and are more influenced by incidental anxiety when making risky decisions. Second, I test whether individuals high on EUA are more affected by integral anxiety when making risky decisions than their lower ability counterparts. The rationale for this prediction is that individuals who have high EUA are able to correctly identify their source of anxiety and, based on perceived relevance, use their integral anxiety to inform their risky decision making whereas those who have low EUA misattribute their anxiety and are less likely to incorporate their integral anxiety into their decision making. In Experiment 1, incidental anxiety reduced risk-taking among individuals with low EUA, but not among their higher ability counterparts. In Experiment 2, the interactive effect of EUA and incidental anxiety on risk-taking was eliminated when I identified the irrelevance of anxiety to the present decision, but it remained when the irrelevance was not identified. To explore the role of EUA in using the adaptive function of emotion in decision making, Experiment 3 assessed whether emotionally intelligent individuals who have high EUA incorporate integral anxiety, as measured by skin conductance responses, into their risk-taking, compared to those with low EUA. Contrary to expectations, the results of Experiment 3 showed that, when EUA was high, there was a negative effect of integral anxiety on risk-taking that was not significant. When EUA was low, there was a significant positive effect of integral anxiety on risk-taking.
The North Caucasus in the Second Half of the Sixteenth Century: Imperial Entanglements and Shifting Loyalties
Keywords: North Caucasus
Ottoman Empire
Muscovy
Safavid Iran
Astrakhan Campaign
Ottoman-Safavid War 1578-1590

The present dissertation seeks to present and analyze the hitherto poorly understood first encounter between the Ottoman Empire and the Tsardom of Muscovy in the North Caucasus from the Muscovites’ annexation of the nearby Khanate of Astrakhan in 1556 and subsequent penetration into this region, to their expulsion from it by the Ottomans in 1605. The study relies on both Ottoman and Muscovite sources, both documentary and narrative, as well as archival and published. The main archival documentary sources are the Ottoman mühimme defters (registers of orders issued by the Imperial Council [Divan-i Hümayun]) and the Muscovite posol’skie knigi (registers of diplomatic documentation, including ambassadorial reports, diplomatic correspondence, and other documents administered by the Ambassadorial Office [Posol’skii Prikaz]). The main narrative sources are sixteenth-century Ottoman and Muscovite chronicles. On the basis of the Ottoman and Muscovite documentary sources it is possible to determine what Ottoman and Muscovite policies in the North Caucasus were, to what degree they were well-formulated, and how they evolved during the aforementioned time period. It becomes clear that Ottoman and Muscovite policies in the Pontic-Caspian steppes and specifically in the North Caucasus had some superficial similarities, but were in essence fundamentally different. Taking into account that it was only after Muscovy’s expansion into the North Caucasus that the Ottomans decided to take an active stand in the north, the dissertation also shows the ways in which Muscovite steppe policy not only affected the political structures on the frontiers but also influenced Ottoman northern policy, and specifically in the North Caucasus. However, this dissertation is not solely a study of an imperial rivalry in a contested frontier zone. The Ottoman and Muscovite involvement brought about changes to the internal dynamics of the polities within the North Caucasus. Lastly, during the first round of this imperial clash, Ottoman and Muscovite presence and sway in the North Caucasus underwent several extreme and unexpected shifts. These shifts and resulting new strategies that the Ottomans and Muscovites had to develop in the North Caucasus played an important role in their future encounters in the northern Black Sea region.