VictorJuiz/thesis huggingface dataset:
Yeast Two-Hybrid is an Effective Platform for the Discovery of Novel Inhibitors of Human Deubiquitinases
Keywords: Biologics
DUBs
Ubiquitin
Yeast

Deubiquitinating enzymes represent attractive therapeutic targets that can be leveraged towards the treatment of a variety of devastating human health disorders. This doctoral thesis recounts the establishment of the well-studied yeast two-hybrid assay as a novel platform for the discovery of ubiquitin variant inhibitors of human Deubiquitinases. Furthermore, I show that ubiquitin variants isolated against the deubiquitinase USP2 in yeast are capable of binding and inhibiting USP2 function in human cells. Taken together, the work described in this thesis highlights the potential of the two-hybrid system to serve as a method to alleviate a formidable bottle-neck that currently obstructs the development of ubiquitin variants and, in conjunction with currently available in vitro screening methods, offers a platform for the discovery of novel inhibitors against human deubiquitinases.
Variational data assimilation of satellite remote sensing observations for improving methane simulations in chemical transport models
Keywords: atmospheric composition
chemical transport modelling
data assimilation
methane emissions
satellite observations
transport errors

Atmospheric concentrations of methane (CH4), the second most important anthropogenic greenhouse gas, have been rapidly rising since 1850, however, the rate of increase has varied in recent decades. In order to attribute these trends, significant effort has been put into characterizing CH4 surface emissions using inverse modelling ("top-down") approaches, which rely on the ability of chemical transport models (CTMs) to simulate atmospheric CH4 fields. However, systematic errors in models can significantly reduce the quality of the CH4 simulation and result in biased CH4 emission estimates. Until now, errors in models have been poorly characterized. The objective of this thesis was to characterize and investigate the origin of the CH4 model errors in the GEOS-Chem CTM and quantify their impact on inferred CH4 emission estimates. The weak constraint four-dimensional variational data assimilation scheme in GEOS-Chem, together with CH4 data from the Greenhouse gases Observing SATellite (GOSAT), were used to characterize model errors in GEOS-Chem at the horizontal resolutions of 4x5 and 2x2.5. Large biases in CH4 were found in the stratosphere and in vertical transport in the troposphere at mid-latitudes. The identified errors were significantly larger at 4x5 than at 2x2.5. It was determined that a major cause of the biases at 4x5 is excessive mixing due to increased numerical diffusion manifested in enhanced stratosphere-troposphere exchange, and stronger quasi-isentropic mixing through the edges of the "tropical pipe" and the polar vortex in the stratosphere. Coarsening of the model grid also weakened vertical transport in the troposphere due to the loss of advective air mass fluxes and sub-grid tracer eddy mass fluxes. A key outcome of this work is the recommendation that the 4x5 version of GEOS-Chem should not be used for inverse modeling of CH4 emissions. The thesis also investigated the sensitivity of North American CH4 emission estimates in the nested version of GEOS-Chem (at the 0.5x0.67) to biases in boundary conditions from the coarse global resolution model. It was shown that biases not fully mitigated in the global CH4 simulation could result in biases as large as 30-35% in monthly mean surface emission estimates on local to regional scales.
Biogenesis and Function of Human Centriolar Appendages
Keywords: BioID
Centriolar Appendages
Centrosome
CEP128
CEP19
Cilia

Centrosomes are the major microtubule organizing centers in animal cells. Each centrosome comprises of two centrioles that are embedded in the pericentriolar material from which microtubules emanate. The two centrioles are structurally and functionally distinct, with the older (mother) centriole harboring protein structures at its distal end termed the centriolar appendages. These proteins function in the formation of cilia, which play pivotal roles during development and adult tissue homeostasis. Mutations in genes affecting the formation or function of cilia cause a plethora of genetic diseases, collectively termed ciliopathies. Therefore, understanding the precise composition and function of centriolar appendage proteins in the development of cilia is crucial in order to better understand the molecular pathways underlying ciliopathies for targeted treatment. Towards this goal, my thesis focuses on defining a protein interaction network for human centriolar appendage proteins, and understanding the molecular mechanisms by which they regulate ciliogenesis. Here, I used BioID to define the protein proximity interaction network for centriolar appendage proteins, and identified C3ORF14 as a candidate new component of these proteins. Furthermore, a functional RNAi screen performed on a subset of members of this interactome identified potential novel regulators of ciliogenesis, and a role for CEP128, a centriolar appendage protein, in the negative regulation of ciliogenesis was described for the first time. In addition, I performed detailed molecular assays to characterize the molecular function of a novel positive regulator of ciliogenesis, CEP19. Combining proteomics, molecular, cellular and imaging assays, I described a role for CEP19, and its interaction partners FOP and CEP350 in regulating the early steps of cilia formation. Collectively, the data presented in this thesis provides new insights into the protein interaction network of centriolar appendage proteins and the function of CEP19 in ciliogenesis. The results herein represent profiling of the protein proximity interaction network of centriolar appendage proteins and, combined with functional analysis, the identification and characterization of novel regulators of ciliogenesis.
In the Breath of Learning: Place-based social movements, Learning, and Prefiguration of Other Worlds
Keywords: Adult Learning
Experiential Learning
Indigenous Research Methods
Situated Learning
Social Movement Learning
Social Movements

Social movements have been and continue to be an integral part of the lifeworld as they create and promote conditions for the transformation of micro and macro aspects of socio-ecological relationships. From the vantage point of the present, we can argue that it is through the work and agitation of feminist, civil rights, LGBTQ, anti-colonial, socialist and environmentalist social movements (among others) that we have experienced socially just changes around the world. The study of social movements is therefore critical for learning about the knowledge-practices necessary to achieve socially just change. This project sought to explore, understand and conceptualize the epistemic ecologies of place-based social movements whose work centers the construction of urgently needed life-affirming human knowledge-practices. Specifically, it sought to illuminate on the scarcely studied connections among learning, knowledge, and society, by examining the social construction of reality in the context of social movement action. The flesh and blood of the project come from the work of social actors in Kufunda Learning Movement and my organizing with Ubuntu Learning Village. The study found that in these contexts, social movement actors are learning and constructing emancipatory knowledge-practices through their engagement with place-based social action. By means of learning through practice, reflection and embodiment, the actors produce and develop practices, skills, and processes that address ecological, political, social and economic relationships. In doing so, they produce subjectivities and critical capacities that enable Other social and political ecologies and societies to emerge. Beyond the learning by movement actors and people that interact with the movement, the study argues that these movements are proposals of counterhegemonic life-affirming realities. Ultimately, Kufunda and Ubuntu knowledge-practices are useful for the movements, the society within which the movements are doing work and the global community, to the extent that their knowledge-practices have analytic validity for social theory.
Ovid's Visceral Reactions: Reproduction, Domestic Violence, and Civil War
Keywords: Augustus
fertility
Latin literature
Ovid
Roman poetry
viscera

Throughout a body of poetic texts composed from the late first century B.C.E. to the early first century C.E., the Roman poet Ovid enacted a semantic shift upon the Latin word viscera. Traditionally denoting the vital inner organs of a human or animal, viscera appear in Ovidian texts as metaphors for wombs and children. This dissertation demonstrates that these visceral reproductive bodies are deployed specifically in contexts of domestic violence and civic discord. Almost without exception, visceral wombs and visceral children in Ovidian mythography mark acts of violation that threaten familial bonds and presage the civic conflicts that tear communities apart from within. Against the backdrop of a nascent dynasty whose program of rebuilding after decades of civil war exerted pressure on its citizens to produce numerous children, Ovid’s visceral bodies link reproduction to destruction rather than renewal. At the end of his career, the author in exile employed viscera as a figure for his own poetic texts, implicating those dangers associated with sexual reproduction in the act of authorial production. Ovid’s new visceral metaphors continue to resonate in later Julio-Claudian and Flavian literature, from the domestic bloodshed of Senecan tragedy to Lucanian civil war epic to an account of private grief in Quintilian’s rhetorical handbook. In the end, these visceral bodies are demonstrative of a sharpening of Roman poetics around abortion, fertility, and women’s bodies in the Augustan period. They serve as a useful point of contact with the ideological substrates of the political, cultural, and social environment in which they developed, indicating to us first what is Augustan about Ovid, and then what is Ovidian about the poet’s literary successors.
Asymptotic Analysis of Locally Linear Embedding
Keywords: Differential Geometry
Laplace Beltrami Operator
Manifold Learning

Since its introduction in 2000, locally linear embedding (LLE) algorithm has been widely applied in data science. In this thesis, we provide an asymptotical analysis of LLE under the manifold setup. First, by study the regularized barycentric problem, we derive the corresponding kernel function of LLE. Second, we show that when the point cloud is sampled from a general closed manifold, asymptotically LLE algorithm does not always recover the Laplace-Beltrami operator, and the result may depend on the non-uniform sampling. We demonstrate that a careful choosing of the regularization is necessary to ensure the recovery of the Laplace-Beltrami operator. A comparison with the other commonly applied nonlinear algorithms, particularly the diffusion map, is provided. Moreover, we discuss the relationship between two common nearest neighbor search schemes and the relationship of LLE with the locally linear regression. At last, we consider the case when the point cloud is sampled from a manifold with boundary. We show that if the regularization is chosen correctly, LLE algorithm asymptotically recovers a linear second order differential operator with ``free'' boundary condition. Such operator coincides with Laplace-Beltrami operator in the interior of the manifold. We further modify LLE algorithm to the Dirichlet Graph Laplacian algorithm which can be used to recover the Laplace-Beltrami operator of the manifold with Dirichlet boundary condition.
Molecular Mechanisms of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: New Insights into the Formation of TDP-43 Protein Assemblies
Keywords: amyotrophic lateral sclerosis
fluorescence microscopy
neurodegeneration
protein misfolding
proteomics
TDP-43

Advances in modern medicine in the past century have dramatically improved the average life expectancy in the western world. Unfortunately, the molecular mechanisms that maintain the integrity of proteins in the body appear to be unable to keep pace. This has led to a growing prevalence of late-onset diseases involving abnormal accumulation of proteins, especially in the last century. The increase in occurrence of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and transmissible spongiform encephalopathies such as prion disease, has become a great burden to the healthcare system. All of these diseases are currently incurable and fatal, but they share the common hallmark of misfolding and aggregation of proteins within the effected neurons. The discovery and characterization of such proteins have often led to the identification of potential targets for treatment and drug design. In the case of ALS, progressive death of upper and lower motor neurons leads to full-body paralysis, and patient death from respiratory failure. The cause of ALS is currently unknown, but remarkably, regardless of the type of ALS (familial or sporadic), the RNA binding protein, TDP-43, is found in 97% of cases as neuronal inclusions, suggesting a mechanistic role in disease pathogenesis. In this thesis, several techniques are used to enable detailed biophysical characterization the TDP-43 aggregation process in solution and in model membranless organelles. Equilibrium turbidity measurements of the protein under aggregating conditions and the inhibitory effects of native-state stabilizing oligonucleotides on aggregation are presented. The modulatory effects of physiological concentrations of electrolytes on TDP-43 aggregation and their implications are also discussed. A novel technique called spatially targeted optical microproteomics (STOMP) is presented as a method to interrogate the proteomic contents of small cellular features in mammalian tissue in hope of identifying common proteins in neuronal inclusions and stress granules. Although the STOMP technique still requires refinement, the biophysical studies on TDP-43 presented here begin to unravel the complex and largely unknown etiology of what is currently a devastating and incurable disease.
Investigating the Combined Impact of Cognitively Guided Instruction and Backward Design model in Mathematics on Teachers of Grade 3 students
Keywords: Backward Design
CGI
Grade 3
Mathematics
Student Achievement
Teacher Performance

This study investigated the effectiveness of combining the Backward Design model and Cognitively Guided Instruction (CGI) in elementary school mathematics classrooms. The study employs a case study model of four Grade 3 Elementary teachers at two different schools and the impact this intervention has on teachers’ mathematics teaching practices and student performance in this area. This intervention utilizes Wiggins and McTighe’s (2005) Backward Design model as a framework to plan, teach, and assess a unit on multiplication, while embedding Carpenter et al.’s (2014) CGI to examine its effectiveness in improving teacher practice and student performance and achievement in elementary mathematics. The findings of this study demonstrate that the delivery of this intervention through professional development can be effective, provided that teachers dedicate adequate time, support, and resources to the implementation of the intervention. Moreover, upon successful implementation of this intervention, the findings of this study suggest: (1) teacher perception of improved student performance; (2) increased student engagement in mathematics; (3) changed teacher practices that include more diverse activities and assessment measures; (4) increased teachers’ knowledge, both pedagogically and in the mathematics content area; and (5) that using the intervention and teaching grade 3 students computational skills through problem-solving questions is a more effective means to teaching students each skill separately.
Participation, positioning, and power: Opportunities to learn in a university Kinesiology Classroom
Keywords: equity
learning sciences
opportunities to learn
science education
sociocultural theory
university education

Past studies in science education research have documented that people of colour and women continue to be underrepresented in science-related university programmes and careers. To better understand issues of equity and student achievement, providing equitable opportunities to learn (OTL) in diverse, content-focused classrooms has been recognized as an important aim in educational research. This critical microethnographic study examines a Canadian, undergraduate, Kinesiology classroom and how the professor’s framing of science learning made space for a range of OTL. Then I explore how students’ navigation of scientific discussions shaped their access to particular OTL. Drawing from cultural-historical activity theory and positioning theory, this dissertation brings into focus the sociohistorical and discursive practices of students and teachers in a science classroom. The research draws data from classroom videotapes, interviews, and stimulated recalls, wherein two participants were the foci of analysis. The analyses consider students’ verbal and non-verbal acts of positioning, highlighting how these positions can facilitate and/or constrained their access to OTL. In one group, a focal student appeared to take up the position of a facilitator, and in another, there appeared to be no expert or facilitator. The second student adopted a powerful role in one activity, then shifted from an initially more passive role to a mediator position in another group. My findings show how a common task led to differential contexts for learning. In particular, conflicts and student differential uptake of positions in small-group settings are examined for their ability to potentially foster unique OTL. My study’s theoretical contributions include a synthesis of sociocultural theories of learning, as well as how these theories can be strengthened through sustained attention to multi- levels of inquiry. The different grains of video analysis afford a broader look at how students learn together in scientific discussions; what resources they draw upon to make meaning; how they negotiate the multiple, interactional demands of the task; and how power and social relations shape available OTL. Implications for science education research are also raised, including suggestions for a greater analytic focus on student-led spaces, and bringing together conversations of learning, identity, and power.
Faculty Narratives of Disability in Academic Work
Keywords: disability avoidance
diversability
neoliberalism
performativity

In the neoliberal academy, professors who disclose any form of impairment risk raising concerns about their fitness to perform their jobs. Academics are expected to deliver highly measurable outcomes from their work in order to build a positive reputation among their peers. But given the negativity that typically characterizes the disability discourse in Western cultures, it is all too easy for the scholarly community to infer that differentness equates to ineptness. Thus, individualist and ableist discourses are central to the discussion of power relations and care of the self in the contemporary academy. The focus of this doctoral thesis is “diversable” professors performing under neoliberal academic regimes. The term “diversability” is used to designate people with disabilities—particularly of an invisible nature—while debunking the fallacious connotation of incompetence habitually attached to their differentness. Combining self-narrative and postmodern-grounded theory, this study derives valuable insights from the stories of 16 professors, both tenured and untenured, who reveal how they navigate disability, as well as the intersecting dimensions of differentness attached to their self-identities. The findings suggest that diversable professors, in spite of an academic environment embedded in disability avoidance—and the usual structural contingencies that can prevent scholars from fully demonstrating their value—can present counter-narratives that include positive constructions of self-identity as good teachers, researchers and advocates for social justice. This research also uncovers inadequacies in the academy itself—but not without a message of hope for remedial change.
Making and Maintaining Metropolises: Entrepreneurial Municipalism in Turkey
Keywords: Comparative urban politics
Intergovernmental relations
Metropolitan governance
Municipalities
Neoliberal urbanizations
Urban entrepreneurialism

This dissertation explores the implications of the public administration and local governance reforms that took place in Turkey in the mid-2000s with a comparative focus on three major metropolitan cities: İstanbul, İzmir, and Diyarbakır. Engaging with the literatures on state rescaling and urban entrepreneurialism, the author analyzes how reforms transformed municipalities into entrepreneurial organizations primarily concerned with territorial competitiveness of their jurisdictions while the central state repositioned itself as a critical actor in urban policy-making. The dissertation research is guided by three critical aspects of urban governance in Turkey: the changing dynamics of intergovernmental relations (national/local and metropolitan/district), the institutional transformation of municipalities (New Public Management restructuring), and emergent urban policies (city branding initiatives, urban transformation projects, and social services). The author argues that variations across three cities indicate how intergovernmental relations imbued with party politics and the local political context are critical in conditioning the scope and content of entrepreneurial action. The author proposes that studies of neoliberal urbanism, which analytically prioritize the political economy perspective, should put cities back into their national context to capture the political and institutional embeddedness of contemporary neoliberal urban governance.