VictorJuiz/thesis huggingface dataset:
CRISPR-cas9 and TALEN Mediated Gene Editing for Treating Cystic Fibrosis

Cystic Fibrosis (CF) is an inherited monogenic autosomal recessive genetic disease that is most commonly seen in the Caucasian population. CF is caused by mutations along the Cystic Fibrosis Transmembrane Regulator (CFTR) gene which is a channel protein that regulates chloride- secretion. Conventional treatments such as physical therapy, antibiotics, and nutritional care only alleviates symptoms but does not provide a cure. New emerging channel potentiators and correctors slowed disease progression for 90% of patients. Gene therapy is an attractive strategy for treating CF as it treats all mutation classes along the CFTR gene. Targeting the airway stem cells for permanent integration of CFTR gene may provide a long-term cure for CF. In this study, we utilized a helper-depended Adenoviral (HD-Ad) vector system to package both gene editing tools and donor genes into a single vector for delivery, owing to its large carrying capacity (36 kb). TALEN and CRISPR-cas9 were utilized as gene editing tools. We first utilized a LacZ donor system to evaluate integration efficiency before integrating CFTR. We demonstrated 5% integration efficiency at the AAVS1 locus using TALEN and 10% using CRISPR-cas9. In addition, the level of TALEN/CRIPSR-cas9 and vector genome diminishes rapidly following delivery, suggesting expression of these components are transient. We showed CRISPR-cas9 mediated gene editing efficiency can be enhanced by supplying cells with key factors involved in cellular repair pathways, SCR7 (DNA ligase inhibitor), CtIP, and Exo1. Integration of CFTR using both TALEN and CRISPR-cas9 lead to long-term stable CFTR mRNA and protein expression; functional analysis showed 50% CFTR channel function restoration without enhancement and close to 100% channel function rescue with enhancement. Collectively, these data showed feasibility of permanent CFTR integration for future in vivo applications.

Keywords: CFTR
CRISPR-cas9
Gene Editing
Gene Therapy
Genetic Disease
TALEN
Advisor: Hu, Jim
Studio of Nature: The Transformation of Artists' Studios, 1845–1910

"Studio of Nature: The Transformation of Artists' Studios, 1845–1910" examines artists' studios in Britain, France, and the United States from the advent of Realism to the Arts and Crafts movement at the turn of the twentieth century. I consider in particular how changing conceptions of the natural environment in the nineteenth century contributed to the emergence of new studio paradigms. The nineteenth century witnessed a dramatic rise in the number of artists who left the studio to paint outdoors. Artists associated with movements as diverse as the Barbizon School, the Hudson River School, Realism, Pre-Raphaelitism, Naturalism, and Impressionism all engaged in plein-air practice to varying degrees. A close engagement not only with physical nature but also with the ideals it represented guided artists working across a variety of artistic genres. In addition to the continued rise of landscape painting in the nineteenth century, the emergence of Realism challenged inherited notions of the studio as a place of retreat that had prevailed since the Renaissance. The positivism that informed artistic movements around midcentury encouraged a direct engagement with reality. While fragments of the natural world could be brought into the studio for study, by and large the studio separated artists from physical nature. This epistemological shift catalyzed numerous studio innovations that unfolded in the decades that followed: the studio was variously transformed into an optical instrument, a mobile apparatus, a transparent prism, and an agent of social reform. As the identity of the modern artist emerged in the nineteenth century, the studio was reimagined to meet the needs of a new generation of artists. "Studio of Nature: The Transformation of Artists' Studios, 1845–1910" foregrounds the significance of the studio as both a contributor to as well as an index of changing artistic standards in the context of modernity.

Keywords: Landscape
Modern Art
Nature
Nineteenth Century
Studios
Advisor: Cheetham, Mark A
Building Resilience in Virtual Online Networks: A Case Study on Developing Resilience in Digital Response Networks (DRNS) through Networked Operational Resilience (NOR)

As society becomes increasingly embedded in a complex array of networks, connected within and across physical and virtual, online and offline domains, the risk implications need to be understood. The pace of innovation exceeds the rate it can be studied, however, and risks are progressively difficult to identify and characterize. Managing unexpected risk can be accomplished largely through resilience (Weick Sutcliffe, 2011; McManus, Seville, Vargo, 2008). All networks possess some level of resilience (Weick Sutcliffe, 2011); yet, little is known about why some networks collapse and others succeed. Building this understanding involves identifying what resilience looks like in complex networks like virtual online networks, specifically the characteristics that define a resilient network and the measures and approaches to developing resilience. Yet little research exists supporting the assessment and development of resilience in virtual online networks. This manuscript-based thesis includes four research papers focused on the assessment and development of resilience in virtual online networks. Contextual research consists of multiple-case study of Digital Response Networks (DRNs) — a term coined in this research. DRNs are citizen-driven networks that work together online during crises to support affected communities and formal responders. Theoretical research consisted of theory creation which combined original network, risk and resilience frameworks with Operational- Resilience (OR) theory to develop the Networked Operational Resilience (NOR) framework. NOR provides a four-step guide to developing resilience in complex networks like DRNs; resilience is thus developed by defining an operation in-situ (as part of the broader network), evaluating risk while considering inherent resilience, and capturing, sharing and importing requirements for resilient operations (through the tableau) across a network. Research suggests that some networks may be more resilient than others due to the relationship between their network configuration and resilience characteristics. Eighteen network traits that can build resilience capability in a network were identified. Clear links are made between each of these characteristics and the inherent characteristics of resilience that accompany them. One network is deemed more resilient than another based on the frequency and distribution of each of these resilience characteristics.

Keywords: Community Behaviour
Disaster Management
Humanitarian Technologies
Networks
Resilience
Risk
Advisor: Deibert, Ronald
Raising a Question Mark: Disability and Textual Recalibration in Canadian Fiction and Film

This study considers how the disabled child is alternately depicted as a question mark of uncertain form and value and as a prosthetic aid to narrative in Canadian fiction and film. Since Lee Edelman’s manifesto against “reproductive futurism” in 2004’s No Future: Queer Theory and the Death Drive, children have been the site of discursive debates about the future in queer theory and beyond. Drawing on disability studies scholarship about literature, this thesis positions the disabled child at the frontier of these discursive debates about what viable lives can be projected into the future. Examining depictions of the disabled child in twentieth- and twenty-first-century Canadian fiction and film, I argue that disabled children are chimeric figures who both facilitate and disrupt narratives of generation and inheritance. The disabled child, I show, glances back on a preceding generation’s yearnings and malfeasances while giving shape to a future that is often frightening but is nevertheless charged with ambivalent potential. My first chapter highlights the depiction of arrested adults frozen in childhood by physical and cognitive disabilities in Irene Baird’s Waste Heritage (1938) and Hugh MacLennan’s Barometer Rising (1941), novels about the state’s relationship to the vulnerable citizens under its custodial powers. My second chapter examines how Margaret Laurence’s The Diviners (1974) and Joy Kogawa’s Obasan (1981) focus their critical gaze on the state’s violent dereliction of care toward its vulnerable citizens through the precarious figure of the racialized disabled child who embodies either a redemptive or an impaired future. In chapter three I examine how the long hand of the state extends into physicians and families in texts since the 1990s, proposing that Barbara Gowdy’s short story “Sylvie” (1992) and Kathleen Winter’s novel Annabel (2010) privilege the singularity of disabled children despite medical interventions to police them. Finally, chapter four evaluates science fiction and horror as capacious generic venues to think about the polysemous nature of the disabled child, juxtaposing David Cronenberg’s film The Fly (1986) and Vincenzo Natali’s Splice (2010) to show how eugenic anxieties about disability are simultaneously past, present, and future.

Keywords: Canadian film
Canadian literature
Disability
Disability studies
Representations of children
Advisor: Goldman, Marlene
Curating Law: Museums as Partners in the International Human Rights Project

Over the past 30 years, a growing number of human rights museums have stepped into the fray of the international human rights project. This dissertation explores the surprising ways that the history, theory, and practices of human rights museums and international human rights law (IHRL) are interrelated. Part I reviews the history of IHRL and identifies its structure and major actors, in order to establish the framework in which human rights museums now play a role. I then review the history of the museum as a political institution, including the type of human rights focused museums that have evolved since WWII, and the particular practices in which they are engaged. Part II tests human rights museum practices against three serious challenges for human rights law: (1) its claim to universality; (2) its lack of effectiveness; and (3) its position within the structures of state sovereignty. In Chapters 4-6, I rely on legal, political, cultural and critical theories to show how museum practices either support or combat critiques of IHRL. Part III is motivated by a desire to identify the ways in which museums influence actors, from individual visitors to larger communities, to the international human rights system. In order to move from the personal to the global levels of influence, Chapters 7-8 rely on legal theories about the construction and meaning of legal norms and the organizational theory of Etienne Wenger, showing the breadth and depth of museum work as it touches upon many levels of human rights practice. The dissertation concludes with a plea for further interdisciplinary exchange in order to solve the complex problems posed by human rights violations. Legal institutions should recognize museums as welcome partners to the human rights project and museums should be conscious of their impact on community understandings of the importance of the rule of law to the realization of human rights. Human rights norms should be ingrained in multiple sites and institutions throughout our society, so that changing the law into a force that oppresses some peoples’ rights is an affront to society’s values.

Keywords: Community of Practice
Human rights
Law
Museums
Norms
Advisor: Brunnée, Jutta
Macklem, Patrick
Defining, Refining, and Enacting Religious Reflexivities in Pakistani-Canadian Muslim Families

Political and popular discourse maintain Orientalist myths about Muslims as uniformly and fatalistically driven by a monolithic Islam, fueling a clash of civilizations. While researchers disrupt this Orientalist narrative by underscoring the presence of Muslim “reflexivity,” or the critical engagement with religious identities, beliefs, and practices, they nevertheless unintentionally reify a uniform Muslim reflexivity. This dissertation is the first empirically based study that demonstrates the social patterns of multiple forms of Muslim reflexivities. I highlight two patterns of reflexivities that relate to different approaches to religion: orthodox and heterodox. I further refine these patterns by highlighting how group and individual statuses shape social location, and thus subjectivity. I draw on theories of racialization and gender and I utilize a sample of 56 currently and previously married Pakistani Canadian Muslims to parse differences between orthodox and heterodox reflexivities and explore how divergent approaches to religion coincide with contrary patterns. These patterns are complicated by group identity for minorities within minorities (e.g., Shias) and by individual statuses (e.g., previously married women). In order to understand these divergent patterns, I extend the concept of Muslim reflexivity by incorporating a religious approach. Orthodox reflexive Muslim participants, who view one approach as correct, are preoccupied with authority given their identification with a marginalized minority group. Thus, they perceive ethnic boundaries as bright and gender boundaries as rigid. The focus of their reflexivity is dawat, or teaching others about the “true” Islam. This contrasts with heterodox reflexive Muslim participants, who view multiple approaches as correct. They do not perceive their minority group as being threatened, and thus do not seek out authority to legitimize their identity. In turn, they perceive ethnic boundaries as blurred, and maintain gender fluid attitudes and practices. The focus of their reflexivity is akhlaq, or having polite manners and ensuring mutually satisfying intimate relations. I conclude by discussing theoretical contributions and policy implications, cautioning against conflating categories of practice and analysis, and also problematizing liberal feminist approaches that pathologize Islam in efforts to ‘liberate Muslim women.’

Keywords: family
minority
Muslim
reflexivity
Advisor: Salem, Rania H
Korteweg, Anna C
RARchive Fever: The Materiality of Videogames

The shaping of videogames by material conditions can be uncovered by comparing works across multiple platforms through something analogous to textual criticism: one must understand the digital equivalents of bibliographical codes and be able to relate them to the processes through which players interact with videogames. In this thesis, I extend the siloed approach of Platform Studies and draw on evidence from the past half-century to examine the diverse codes that shape the meaning-making of videogames. Chapter One posits that digital storage media have a knowable topography, and that videogames provide an ideal tool to visualise and navigate it. Additionally, this chapter demonstrates that understanding this topography can enhance our appreciation of videogames by detailing how storage-based glitches make the contours of the storage visible to us. In Chapter Two, I examine what is hidden in digital texts, including comments as well as decoupled portions of code. Although such information cannot be seen by those unaware of how displayed information only partially reflects the content of digital files, it can have industry-shaping consequences. An “Interlude” section concludes my study of digital storage and data and introduces the study of further components, including hardware and print matter. Chapter Three explores mobile devices as collections of sensors continually gathering data. Focussing on the game République, I study how such data can be used without the knowledge of and contrary to the wishes of a device’s owner. République provides a model for making visible the processes in a player’s phone, so as to challenge her trust of her device. Finally, in Chapter Four, I turn to an early Computer Role-Playing Game, The Temple of Apshai. Studying its manual, I demonstrate that print materials can be integral to videogames: they reveal connections to print traditions and allow the games to surpass the limitations of their storage media. My comparative approach to platforms and eras serves to illuminate the nuances of digital materiality in videogames. Advancing our knowledge of this field of study is vital at a time when access to the original objects is waning.

Keywords: Bibliography
Computers
Materiality
Platform Studies
Videogames
Video Games
Advisor: McLeod, Randall
Humanitarian Governance Experiments: INGO Power and the War in Syria

After the War in Syria broke out in 2011, new needs emerged amongst Syrian refugees in Lebanon and Jordan. They presented with high rates of disability and of non-communicable disease, like asthma, diabetes, and cardiovascular disease. Local actors, Syrian doctors, and the World Health Organization (WHO) called for response to these unmet needs. Yet, standard repertoires of response dominated as international non-governmental organizations (INGOs) offered the kinds of care they were accustomed to offering in other contexts, such as first aid care and primary healthcare response. This behaviour is not uncommon to INGOs, nor should it have been unexpected. Scholars have shown that time and security constraints during emergency, humanitarian operations limit opportunities to reflect and learn. What was unexpected was a set of more transformative changes by service-delivery INGOs that followed between one and four years into the crisis, or humanitarian governance experiments (HGEs). These were first moves into new areas of service-delivery and rulemaking that altered the range of behaviours available to potential recipients, were meant to provide assistance across borders, and claimed new rights to govern populations or aspects of their lives. Aid workers deliberately and consciously contested the limits of status quo response, moving their organizations into areas of service-delivery previously considered the domain of states and outside of the humanitarian scope. It is this increasingly governmental activity by INGOs that this dissertation explores. It adds important conceptual and empirical clarity to the question: why is there variation in the timing of new behaviours across INGOs of similar size and engaged in the health sector? Drawing on comparison of those processes and factors that make experiments by three humanitarian organizations – Doctors Without Borders / Médecins Sans Frontières (MSF), Save the Children International (SCI), and the International Committee of the Red Cross and Red Crescent (ICRC) – possible, my research shows that an organization that decentralizes power to the field and is home to bottom-up channels of expert communication is most likely to experiment when experiencing insecurity. Findings contribute to studies of aid and humanitarianism, INGO behaviour in international relations theory, and governance.

Keywords: Governance
Humanitarian
INGO
Middle East
Syrian refugees
Advisor: Wong, Joseph
Hoffmann, Matthew
The Colonizer The Colonizer Who Refuses: Cultural Production and Colonial Crisis at Oka, Ipperwash, Burnt Church Caledonia

This study examines white settler responses to the Oka, Ipperwash, Burnt Church, and Caledonia Crises. Listed as the quintessential examples of contemporary “Indian Crises” in Canada, I argue these events are in fact colonial crises, produced by colonizers in an attempt to manage Indigenous resistance and the “Indian question.” Colonial crises are sites of inordinate state and mob violence, as well as anti-Native activism, however, colonizers can be found on all sides of the (proverbial) barricades as aggressors, “peacekeepers,” and allies. These four crises are sites of extraordinary white settler activity and production, where techniques and modes of power—colonial governmentalities—are (re)fashioned. To examine this spectrum of white settler responses, I assembled a corpus of materials produced concerning each crisis. Using discourse analysis and genealogy to study white settler behaviours and discursive products, the corpus reveals that whether symbolising current “Indian-White” relations or the “ugly events” from which the nation has evolved, the four crises are key to stories of colonial progress and improvement, even if in that story, progress is rendered as having gone too far. The crises are cited by a plethora of colonizers as proof of the necessity of their particular political approach to (re)managing Indigenous-settler relations. These management strategies include calls for heightened use of state force to quell Indigenous resistance, demands for the state to engage in “negotiations, not confrontation,” as well as calls for decolonization. Attentive to the discursive parameters of white settler responses, I trace three figures in a continuum of colonizers: the anti-Native colonizer, the liberal colonizer, and borrowing from Albert Memmi, the colonizer who refuses. The corpus is utilized to pattern behaviours and trace colonial structures of feeling across each figure to understand the spatio-temporal dimensions that shape when and where “pro-Native” and anti-Native sentiment emerge. Interrupting the narratives of colonial progress in the “age of reconciliation,” I argue it is imperative Memmi’s colonizer who refuses be historicized in a white settler state not as a new arrival or new subject but as a colonizer whose rejection of colonialism has always been central to the management of an ongoing colonialism.

Keywords: Colonial Crises
Colonial violence
Colonizer who refuses
Indigenous Resistance
Indigenous-Settler Relations
Settler Colonialism
Advisor: Razack, Sherene
Open Borders, Local Closures: Decentralization and The Politics of Local Responses to the Syrian Refugee Influx in Lebanon

The ongoing Syrian civil war has been characterized as the greatest crisis of forced displacement since the Second World War, and has disproportionately affected neighboring countries who host the vast majority of displaced Syrians. As a result, Lebanon, a country of nearly four million citizens, saw its population grow by nearly a third in less than three years, and quickly became the largest per capita host of refugees in the world. At its core, this dissertation is driven by a desire to understand how a country such as Lebanon, a near-archetype of what political scientists often call a “weak state,” dealt with the influx of an unprecedented number of refugees in a remarkably short period of time. Neighbouring Jordan and Turkey, the second and third largest hosts of Syrians per capita, moved quickly to implement national plans and policies, build formal refugee camps, and regulate the presence of Syrians on their territory. In contrast, in Lebanon, the over 1.1 million Syrian refugees who entered the country faced what has been called a ``policy of no policy." Among the most important elements of this policy was the refusal to build formal refugee camps. The result was that Syrian refugees self-settled across Lebanon's over 1100 municipalities, which in turn became key actors in the governance of Syrians in the country. Three main research questions structure my analysis: (1) How do so-called ``weak" states manage and govern migrants on their territory? (2) What explains variation in sub-national migration policies? (3) Finally, in what ways do sub-national practices and policies challenge, strengthen, and potentially drive national policy with regards to migrants and refugees? In answering these questions, I find that explaining a state's response to large-scale displacement must take into account the multiple scales at which migrants are governed. More specifically, it is only by looking below the central state that ostensible paradoxes between relative openness at the national level, and tensions and restrictions at the local level, can be understood. Through locally-grounded analysis, I find that so-called open borders can co-exist and even co-constitute local closures.

Keywords: Lebanon
local governance
Middle East
migration
refugees
Syria
Advisor: Schatz, Edward