VictorJuiz/thesis huggingface dataset:
The Role of Telomerase Reverse Transcriptase in Tumorigenisis
Keywords: Telomerase
Telomeres
Tumorigenesis
Transformation
hTERT
Cre

The acquisition and maintenance of cell division potential are important characteristics of tumorigenesis. Human telomerase reverse transcriptase (TERT) and telomerase RNA (TR) can immortalize cells through telomere maintenance, and telomerase activity is one factor that contributes to the in vitro transformation of normal cells. In vitro and in vivo evidence suggest that telomerase maintains telomeres as a functional multimer. In addition, hTERT may possess telomere maintenance-independent functions. To examine the effects of hTERT loss upon an in vitro generated tumorigenic cell line we created a tumorigenic cell line from human embryonic kidney cells through expression of the SV40 early region, H-RasG12V and a Cre-mediated excisable hTERT. These immortalized cells exhibited robust anchorage-independent colony growth and tumor formation in immuno-deficient mice. Cre recombinase expression resulted in the excision of hTERT from the tumorigenic cell lines, restoring cell mortality. A return to immortality was conferred by the re-introduction of wild-type hTERT, but not with hTERT point mutations in the N-terminus (hTEN) and reverse transcriptase (RT) domains that impair in vitro telomere elongation activity. The onset of cell mortality was not immediate, and the hTERT-excised tumorigenic cells exhibited clonal variation in the anchorage-independent colony growth assay and upon tumor formation in immuno-deficient mice. We hypothesized that tumorigenic potential was not related strictly to hTERT presence, but rather telomere length and/or integrity. To investigate this possibility we maintained the tumorigenic cell lines in the continuous presence of hTERT to permit telomere elongation prior to hTERT excision; subsequently, after hTERT excision tumor formation persisted, thus demonstrating a dependence on telomere length and not hTERT presence per se. To investigate the functional multimerization of hTERT in vivo we tested if two defective hTERT polypeptides with mutations in the hTEN and RT domains could restore telomere elongation activity in vivo. Unfortunately, during the course of these experiments an unanticipated recombination event occurred that restored a catalytically active hTERT transgene. Further in vivo analysis of hTERT multimerization should be carefully designed, accounting for the selective survival advantage bestowed by wild-type hTERT. This study provides compelling evidence that hTERT does not possess telomere maintenance-independent functions.
Essays in Empirical Development Economics
Keywords: development economics
economic development
education
civil wars
partition
Bosnia
social networks
migration

This thesis consists of three empirical chapters that examine issues in development economics. Chapter 1 focuses on the effects of civil wars on the welfare of individuals. I use a unique data set that contains information on war casualties of the 1992-1995 Bosnian War, and exploit the variation in war intensity and birth cohorts of children, to identify the effects of the war on schooling attainment. I find that cohorts affected by war are less likely to complete secondary schooling, if they resided in municipalities that endured higher levels of war intensity. Ancillary evidence suggests that my estimates are most likely picking up immediate, rather than long-term effects. Furthermore, direct mechanisms such as the destruction of infrastructure and the out-migration of teachers do not seem to matter; instead, the ancillary evidence suggests that youth soldiering may be more important. Chapter 2 studies the impact of the partition which ended the Bosnian War on the post-war provision of public goods at the municipality-level. Comparing trends in the provision of public schooling across partitioned and unpartitioned municipalities during the 1986-2006 period, I find that partitioned municipalities provide 58 percent more primary schools and 37 percent more teachers (per capita). I also find evidence which suggests that convergent preferences - operating via ethnic politics - for ethnically oriented schools may be an important driver of the results, although I cannot rule out the possibility of mechanical explanations. In addition, as the increase in public goods provision may be ethnically oriented, only the ethnic majority profits from this arrangement. Chapter 3 provides an estimation of network effects among rural-urban migrants from Nang Rong, Thailand, by using heterogeneous migration responses to regional rainfall shocks among villagers as exogenous variation affecting network size. I find that social networks significantly reduce the duration of job search, and surprisingly, draw new migrants into the agricultural sector. I argue that this is not because agricultural jobs are more attractive than non-agricultural ones, but rather that my estimates are essentially local average treatment effects that are estimated off agricultural workers who are most affected by rainfall shocks.
Capitalist Transformation and the Evolution of Civil Society in a South Indian Fishery
Keywords: social movements
counter-movement
civil society
Polanyi
fisheries
capitalism

This thesis employs Karl Polanyi’s concept of the double-movement of capitalism to trace the trajectory of a social movement that arose in response to capitalist transformation in the fishery of Kanyakumari district, south India. Beginning in the 1980s, this counter-movement militantly asserted community control over marine resources, arguing that intensified production for new markets should be subordinated to the social imperatives of subsistence and equity. Two decades later, the ambition of “embedding” the market within the community had yielded instead to an adaptation to the market in the language of “professionalization,” self-help, and caste uplift. Polanyi is useful for identifying the constituency for a counter-movement against the market, but tells us little about the social or political complexities of constructing such a movement. To locate the reasons for the decline of the counter-movement in Kanyakumari, I turn therefore to an empirical observation of the civil society within which the counter-movement arose. In doing this, I argue against Partha Chatterjee’s influential view that civil society as a conceptual category does not apply to “popular politics in most of the world,” and is not useful for tracing non-European, post-colonial, and subaltern modernities. By contrast, my case shows the presence of civil society – as a sphere of autonomous and routinized association and publicity – among subaltern groups in rural India. I argue that it is precisely by locating the counter-movement of fishworkers within civil society that one can map the multiple negotiations that take place as subaltern classes are integrated into the market, and into liberal democracy, and explain the difficulties of extending and sustaining the counter-movement itself.
Considering Mobile Devices, Context Awareness, and Mobile Users
Keywords: mobile
context
adaptation

Recent years have seen rapid growth and adoption of powerful mobile devices such as smartphones, equipped with sophisticated input and display systems, and multiple communication technologies. This trend has coincided with the rapid deployment and adoption of high-speed Internet services and web-based applications. While this rapid development of mobile technology has provided great opportunities, it also presents significant new challenges compared to traditional desktop computing. Specifically, unlike the traditional desktop computing experience where users are stationary and physically isolated, users in mobile and social settings can be faced with real time demands for their attention. This thesis examines the relationship between mobile devices, context awareness, and mobile users. We propose the use of physical proximity context to adapt and improve system behavior, and enable mobile users to more effectively access and share content in non-desktop settings. This work identifies three distinct challenges in mobile software, and addresses these challenges using physical proximity context awareness. First we address improvements to mobile node network utilization by using proximity awareness to automatically manage local radio resources. Next we address improvements to mobile web-backed applications and services by enabling social proximity awareness. Finally, we enable greater mobility and physical awareness for visually impaired users on mobile devices by providing an interface which enables exploration of spatial geometric layouts.
Dynamics Underlying Interacting Mechanisms of Sexual Selection
Keywords: sexual selection
male-male competition
female choice
redback spider

Sexual selection drives the evolution of male morphology, life history, physiology, and behaviour across taxa. Here I examine the mechanisms of sexual selection that arise at various stages in mating interactions to identify congruence or conflict between the traits selected by choice and competition. I first examine plasticity of developing male Australian redback spiders (Latrodectus hasselti) and show that male metabolic rates vary adaptively to facilitate the scramble to reach virgins. Next, I show that females cease sex pheromone production after mating and re-advertise receptivity later in their reproductive season effectively creating two windows in which males may compete. I show that females discriminate against males that do not meet a threshold courtship duration suggesting that courtship is the trait selected through choice. However, male-male competition leads to reductions in courtship effort provided to females. During the first window paternity is split equally if rival males mate in quick succession with a virgin female. However, if the second mating is delayed, there is a strong bias in the paternity of the second male. A delay in the second mating is beneficial to females as it reduces longevity costs of polyandry. However, delays in the initial mating decrease female longevity, likely because of elevated metabolic rates of virgins. My research shows that the trait favoured by female choice is in opposition to selection via male-male competition. Females’ sex pheromone production yields windows during which mating will optimize female, but not male, fitness. Studies that isolate the mechanisms of sexual selection are valuable in that they can identify the traits under selection. However, my research shows that considering these processes in isolation can lead to incorrect inferences about the net effect of sexual selection.
Mouse Medial-prefrontal Cortex Involvement in Trace Fear Memory during Wakefulness and Sleep
Keywords: Prefrontal
Trace fear

This thesis represents a culmination of work which seeks to examine the prelimbic and anterior cingulate cortex (ACC) during trace fear memory across sleep and wakefulness states. In order to accomplish this task, a technical platform needed to be developed. Accordingly, the first chapter demonstrates that fear behavior can recorded utilizing neck electromyography (EMG). The second chapter examines the role of the ACC in trace fear memory, discovering that many neurons have premotor activity related to freezing behavior. Additionally, auditory-evoked potentials in the ACC demonstrate learning curves which match learning curves of fear. We suggest that the ACC is involved in affective-motor integration. The third chapter examines how genetic enhancement of trace fear learning, with calcium/calmodulin-dependent protein kinase IV (CaMKIV) over-expressed mice, can influence electro-cortical potentials during wakefulness, learning and sleep. We found that CaMKIV potentiates electro-cortical brain waves during learning and sleep. In particular 4-7.5Hz rhythms were potentiated in CaMKIV over-expressed mice during learning, and are likely to be localized to regions of the prelimbic cortex. Taken together the results of this thesis demonstrate that the trace fear memory paradigm engages the ACC and prelimbic regions, as evidenced at the single cell and cortical field potential level, for sensory-affective and premotor functions related to anticipating painful stimulation. CaMKIV appears to be a protein which modulates learning and electro-cortical potentials and may be a potential target for sleep-dependent memory consolidation in the prefrontal cortex.
Ramsey Property of Posets and Related Structures
Keywords: posets
Ramsey property

We study several classes of finite posets equipped with linear orderings. We examine these classes according to the Ramsey and the ordering property. As an application we give several new extremely amenable groups of automorphisms of countable structures and compute several new universal minimal flows for such groups. The technique that we develop is also useful for studying classes of structures related to posets, such as quasi-orderings.
Understanding the Moral Nature of Intrapartum Nursing: Relationships, Identities and Values
Keywords: Intrapartum nursing, childbirth, choice, nursing ethics, moral responsibilities, narrative, Margaret Urban Walker

The establishment of effective relationships is fundamental to good nursing practice and the fulfillment of nurses’ moral responsibilities. While intrapartum nurses are uniquely placed to establish relationships that can directly influence the woman’s experience of childbirth, there has been limited investigation of the relationships, identities and values that underlie nurses’ varied approaches and responses to labouring women. The purpose of this study was to explore intrapartum nurses’ understanding of their moral responsibilities from a social-moral perspective, using Margaret Urban Walker’s “expressive-collaborative” model of morality. Interviews were conducted with fourteen registered nurses working in a birthing unit of a Canadian teaching hospital. Four themes were identified that captured nurses’ moral responsibilities, including: organizing and coordinating care, responding to the unpredictable, recognizing limits of responsibilities to others, and negotiating care with women and families. Nurses enacted their moral responsibilities to labouring women in a variety of ways depending on their personal and professional experience, the circumstances, the people involved and the context of care. A key factor influencing responses to women was the degree to which understandings and expectations related to birth were deemed to be reasonable and mutually agreed upon among nurses, physicians, women and their families. Nurses also described limits on their responsibilities to others. Their choice of response to circumstances in which practice was constrained departed from the idealized expectations and ‘expert’ practices often reflected in professional guidelines. While nurses were able to identify contextual influences that constrained their ability to maintain effective relationships with women, the influence of their own values on the care they provided was less apparent. This suggests a need to challenge normative assumptions related to care of women in childbirth, including the provision of choice and family centred care, in order to create environments that can support and sustain practices that build understanding, mutuality and trust between nurses and birthing woman. In addition, given the contested nature of childbirth and the lack of shared understandings of what constitutes ‘best’ care, there is a need to develop collaborative models of inter-professional maternity care that include the voices of women as a central component.
Policing Poverty: Race, Space and the Fear of Crime after the Year of the Gun (2005) in Suburban Toronto
Keywords: urban governance
Toronto

In 2005, firearm homicides in Toronto spiked to unprecedented levels, prompting mainstream media to label 2005 as the ‘Year of the Gun’. While the majority of those killed were young black men in Toronto’s impoverished post-war suburbs, the shooting death of a young white woman downtown reframed the problem of gun violence in popular and policy discourse from the perspective of those it least affected: the predominantly white middle-classes in the gentrified urban core. This dissertation attempts to situate dominant narratives of the problem of gun violence and policy responses to it as an event in a history of Toronto, especially with reference to transformations in urban space and governance. It argues that the Year of the Gun can be understood as a destabilizing moment in the city’s collective history that helped normalize ways of narrating and governing a growing socio-spatial divide between the city and the post-war suburbs. Through analyses of government proceedings, media discourse, social scientific research, participant observation, and key informant interviews it identifies how intersecting discourses, practices and representations framed racialized poverty and crime in ways that further solidified causal links between the two. It offers a history for these causal links, illustrating how race and space have long played a vital role in real and imagined divisions between the city and its suburbs. It explores the formation and administration of three policy approaches responding to the crisis: a municipal policy framework for social investment, a targeted policing strategy, and non-profit faith-based programs for young black men. It analyses how each defined social problems for government in ways that eclipsed broader processes generating social inequality in the city. The findings of this research suggest that dominant narratives and practices governing poverty and crime have prevented public discussions about the racialized architecture of neoliberal urbanism while enforcing one of suburban decline. They have prevented dialogue about the correlation between whiteness and wealth in the core, while enforcing causal relations between blackness, poverty and crime in the suburbs. And they have prevented critiques about the surveillance of the city’s young black men, while enforcing projections of these same men through the prism of masculinist culture.
Role of Lipid Rafts in Enterohemorragic Escherichia coli 0157:H7 Mediated Hijacking of Host Cell Signalling Pathways to Induce Intestinal Injury
Keywords: Escherichia coli O157:H7
Lipid rafts

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a human intestinal pathogen, which can cause severe disease. EHEC O157:H7 is responsible for outbreaks of diarrhea and hemorrhagic colitis. EHEC produces a potent cytotoxin known as Vero (Shiga-like) cytotoxin, which causes diarrhea-associated hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in children. Current treatment remains predominantly supportive in nature because antibiotics and non-steroidal anti-inflammatory drugs exacerbate the condition. Therefore, alternative therapeutic approaches that will prevent the EHEC colonization without the release of toxins need to be delineated. Understanding the pathobiology of disease is likely to yield novel approaches to interrupt the infectious process. My hypothesis was that pathogen-derived effectors associate with lipid rafts and, thereby, promote the recruitment of host signal transduction proteins to lipid rafts in response to EHEC O157:H7 infection. In this thesis, specific host signalling pathways hijacked by EHEC O157:H7, through lipid raft signalling platforms, to elicit pathogenic effects are studied using complementary approaches, including epithelial model cell lines and an animal model of infection (Citrobacter rodentium challenge of mice). A lack of osteopontin resulted in decreased attaching effacing lesions and reduced colonic epithelial cell hyperplasia in response to C. rodentium infection. These findings suggest that C. rodentium, mimicking EHEC O157:H7 infection, is capable of utilizing host cell components to elicit its pathogenic effects. In vitro data showed that EHEC O157:H7 effector proteins manipulate cell signalling through lipid rafts employed as platforms to recruit and activate host second messengers. PKC and PI3K activation led to attaching and effacing lesions, disruption of tight junctions, and the initiation of both innate and adaptive host immune responses. The results pointed towards a role for atypical PKC in EHEC-induced attaching and effacing lesion formation. The role of lipid rafts in EHEC O157:H7 pathogenesis was also studied using Citrobacter rodentium-infected Niemann-pick type C (NPC) mice. Infection of NPC mice, which lack lipid rafts, with C. rodentium resulted in delayed colonization and delayed onset of attaching-effacing lesion formation, compared with infected wild type mice. C. rodentium-infected NPC mice also demonstrated reduced colonic epithelial hyperplasia and decreased secretion of the pro-inflammatory cytokine, interferon-γ. Taken together, the findings presented in this thesis highlight the importance of host cell signal transduction cascades in EHEC O157:H7 disease pathogenesis, and demonstrate a role for lipid rafts and OPN in mediating host cell signaling responses to non-invasive enteric microbial pathogens.
Staging Tudor Royalty: Religious Politics in Stuart Historical Drama (1603-1607)
Keywords: English

Staging Tudor Royalty: Religious Politics in Stuart Historical Drama (1603–1607) examines the plays and pageantry about the Tudor royals in the context of three major events: the Hampton Court Conference (1604), the Anglo-Spanish Peace Negotiations (1603–1604) and the Gunpowder Plot (1605). Chapter 1 provides an historical survey of the political and legal controversies concerning religious belief and practice from Henry VIII’s creation of the royal supremacy (1533–1534) to Elizabeth’s final year as queen (1603). Chapters 2 through 5 comprise four case studies, each of which centres on a play or pageant about the Tudor royals and its relationship to one of the aforementioned events. Chapters 2 and 3 examine Thomas Heywood’s If You Knovv Not Me, You Know No Bodie (1604) and Samuel Rowley’s When You See Me, You Know Me (1604), dramatizations of Elizabeth’s years as princess and the later years of Henry VIII’s reign respectively, in light of the puritan campaigns for church reform and religious toleration surrounding the Hampton Court Conference. Chapter 4 examines the uses of the Tudors in Thomas Dekker’s The Magnificent Entertainment, a detailed account of James’s royal entry of March 1604. In particular, I focus on the London-Dutch community’s celebration of Tudor religious and economic commitments to the Protestant Low Countries in relation to the early Stuart negotiations for an end to the Anglo-Spanish war. Chapter 5 discusses Thomas Dekker’s allegorical rendering of the later decades of Elizabeth’s reign, The VVhore of Babylon (1607), as a commentary on the Stuart government’s response to Jesuit insurgency following the Gunpowder Plot. In order to situate these plays and pageants in their precise contexts, each of the four case studies incorporates a variety of historical evidence ranging from royal proclamations to religious polemics, from stories of martyrdom to state trials. This thesis offers a topical reading of play and pageantry in which the Tudor past engages with the seminal political-religious issues and controversies of early Stuart England.