VictorJuiz/thesis huggingface dataset:
A Novel Gene Therapy Approach Based on Secreted Antiviral Proteins for the Control of HIV Replication
Keywords: Bifunctional entry inhibitor
Fusion inhibitor
Gene therapy
HIV entry
Lentiviral vector
Secreted entry inhibitor

HIV entry into target cells requires the interaction of the HIV envelope glycoprotein (Env) with a primary receptor (CD4) and a co-receptor (most commonly CCR5 or CXCR4). Protein-based HIV entry inhibitors are highly effective in protecting cells from infection. However, their clinical application is limited because their use requires the frequent injection of highly purified proteins. This study focuses on the development of a gene therapy strategy for the delivery of protein-based HIV entry inhibitors. In Chapter 2 we show that an antibody fragment targeting CCR5 (sscFvPRO140) is secreted from gene-modified human cells and can protect unmodified cells from infection. Chapter 3 describes the secretion and antiviral effect of entry inhibitors targeting HIV Env. A soluble receptor (sCD4), sCD4 covalently linked to a fusion inhibitor (sCD4-FIT45) and sCD4 linked to an antibody fragment targeting the co-receptor-binding site (sCD4-scFv17b) were secreted in significant quantities and protected primary HIV target cells from infection. In Chapter 4 we examine the secretion of sCD4 in a mouse model of HIV infection. sCD4 was present in the blood (~100 ng/ml) of mice engrafted with gene-modified hematopoietic stem cells, reduced viral load over time and protected CD4+ T cells from depletion. Chapter 5 describes the use of gene-modified cell lines for the production of secreted human proteins and their small-scale purification from the culture media. In Chapter 6 we further investigate the antiviral potency of sCD4-FIT45. The bifunctional protein inhibited HIV Env-mediated cell fusion and HIV entry of several primary isolates more potently than VRC01, sCD4, or sCD4-scFv17b. Taken together, we have shown that human cells can be engineered to secrete HIV inhibitors. Furthermore, our results highlight the benefit of combining inhibitors that target receptor-binding and membrane fusion.
Stairway to nowhere: Structural incoherencies reveal the role of the medial temporal lobe in visual perception
Keywords: Cognitive Neuroscience
Hippocampus
Medial Temporal Lobe
Neuroimaging
Scene Perception
Visual Perception

Surprisingly little is known about how the brain combines visual elements to form a coherent percept of the surrounding environment. Recent evidence has highlighted a critical role of the medial temporal lobe (MTL) in binding together disparate visual elements into conjunctive representations that supports both declarative memory and some types of perception, suggesting that these regions may play an important role in perceptual coherency. In particular the hippocampus (HC) is hypothesized to support complex spatial perception, in contrast to the perirhinal cortex (PRC) thought to support object perception. In order to investigate scene perception, I have developed a novel experimental paradigm, the impossible scenes task, in which participants are presented with a series of single, unique virtual reality scenes and instructed to indicate whether each was ‘possible’ (i.e. spatially coherent) or ‘impossible’ (i.e. spatially incoherent). In the current dissertation I leverage the impossible scenes task to argue that the HC is sensitive to spatial coherency, and by extension, scene perception. In Chapter 2, univariate analyses of fMRI response to impossible scenes judgments in neurologically healthy young adults (YA) revealed greater HC activity to spatially incoherent than spatially coherent scenes. In Chapter 3, multivariate statistical analyses of these data demonstrated spatial coherency-dependent functional connectivity for the HC, with greater connectivity to posterior visual regions during incoherency detection. In Chapter 4, measures of eye-movements during scene coherency judgments reveal that the observed pattern of response in the HC reported in earlier chapters cannot be accounted for by working memory task demands. In Chapter 5, I contrast performance of healthy older adults (h-OA) thought to have compromised HC function, and OA at-risk for diseased aging (ar- OA) thought to have additional PRC dysfunction, on the impossible scenes task and impossible objects task. I analyzed eye-movements to each task to reveal that, compared to YA, both h-OA and ar-OA, showed an abnormal fixation pattern to impossible scenes, whereas only ar-OA made abnormal fixations to impossible objects. Together, these data speak an important role of the MTL in complex visual perception, and the HC in visual scene perception.
Exploring a Two-Solver Architecture for Clause Learning CSP Solvers
Keywords: Constraint Satisfaction Problems
Satisfiability Problem
Search

Many real world problems can be encoded as Constraint Satisfaction Problems (CSPs). Constraint satisfaction problems contain variables over finite domains, as well as constraints over these variables. There exists many solvers that can solve these problems efficiently. Once these problems are solved, their solutions correspond to solutions of the real world problem the CSP encodes. Similarly, many problems can be encoded as instances of the Satisfiability Problem (SAT). In SAT all the variables are binary propositions, and the only kind of constraint they allow is the disjunction of a set of variables. SAT and CSP are closely related, and they both are NP-complete. These two approaches have their own advantages and disadvantages. SAT solvers perform clause learning, which prevents them from visiting similar subtrees in the search tree. The advantage of CSP solvers is that the CSP instances contain higher level constraints, which allows better reasoning. Recently, methods combining the advantages of SAT and CSP solvers have emerged. In such methods, solvers maintain a propositional representation of the CSP problem, and perform clause learning over this representation. Such solvers are called "clause learning CSP solvers". However, the question of how to handle constraints in such solvers is unresolved. For each constraint, a solver must choose whether to encode the constraint entirely in SAT or use a special purpose propagator, and this choice also determines the propagation strength and efficiency. Different choices perform better in different scenarios, hence hybrid methods which can be adaptive are promising. In this thesis, we propose an alternative architecture for clause learning CSP solvers, which incorporates two solvers of different strength. One of the solvers directs the search using fast and weak propagators. Once it gets into a dead end, it produces a conflict clause, and asks the other solver to enhance it using stronger but slower propagators. In this way, the slower propagators are run only whenever they are likely to be needed, instead of each node in the search tree. We instantiate this architecture in different ways, and perform experiments to demonstrate the trade-offs between these instantiations.
Looking for Work: How Second Generation Caribbean Black Male Youth Make Sense of Social Mobility, Social Networks and Employment Opportunities in Toronto
Keywords: African Caribbea Diaspora Studies
Critical Race Theory
Neoliberalism
Precarious Work
Youth Studies

ABSTRACT This dissertation project examines the ways in which working class Caribbean Black Males Youth (CBMY) that are in precariously employed seek to get full- time employment. These CBMY are subjected to being unprepared to access employment for two main reasons, either they fall into the 50% drop out rate (Allahar, 2010; Dei, 2008; Gordon Zinga, 2012; James, 2011) or these men fall into the 52 % of precariously employed in the Greater Toronto Area (Lewchuck et al., 2014; Block Galabuzi, 2011). Post high school transitions into the job market for these Black Males are expressed through their viewpoints. My research is theoretically grounded in Critical Race Theory in acknowledging that racism is embedded in Canadian life moving to capsulize the various complex ways CBMY navigate the demands of the market place in the city of Toronto. The aim is to conceptualize the meaning making process through key elements (i.e., schooling experiences, family experiences, peers conversations) shaped by their choices on deciding on particular kinds of employment. I argue that dominant social ideals of manhood are influenced by privileged, white, male middle-class standards. I therefore interrogate how CBMY make sense of themselves, either within or outside of these conventional standards of manhood and masculinity as it relates to precarious work. Based on these larger research arguments, I critically examine how CBMY address social issues of mobility, social networks and employment opportunities from their own perspectives.
Visual Scanning and Attentional Biases in Alzheimer's Disease: Assessing Symptoms and Outcomes
Keywords: Alzheimer's disease
cognition
eye-tracking
neuropsychiatric symptoms
visual attention

Current assessments of cognition and behaviour in Alzheimer’s disease (AD) rely on indirect evaluations and are complicated by communication deficits, hampering ability to effectively prescribe and monitor pharmacotherapy. The purpose of this thesis was to determine whether direct measurements of visual scanning behaviour can optimize symptom and outcome assessments in this patient population. In the four studies conducted, a non-verbal eye tracking technique was used to characterize visual scanning behaviour in order to quantify methods of measuring cognition, behaviour and pharmacotherapy-induced changes in AD patients. To evaluate selective attention towards novel stimuli or novelty preference in AD, mild-to-moderate AD patients (n=41) and elderly controls (n=24) viewed novel and repeated images simultaneously. Compared with controls, AD patients spent less time on novel than repeated images (F(1,63)=11.18, p=0.001). Reduced novelty preference was associated with worse cognition (Standardized Mini-Mental State Examination, sMMSE, r(63)=0.29, p
Behind Closed Doors: How the Peer-review Process Works and How Arts Councils Make Decisions About Arts Funding
Keywords: arts funding
Canada
decision making
groupthink
peer review
symbolic power

Visual artists have often expressed discouragement and mistrust of the peer-review process in the arts. In conversations and in interviews I conducted in 2012, visual artists explained that they mistrusted the decision-making granting system because they did not understand art councils’ categorization policies and processes. Once artists were denied funding, they often did not reapply. They wished that they had learned the reason for being turned down. As a visual artist, I share this sentiment. Arts grants applications are assessed under the peer-review model. The peer-review model is a closed-door process. Peer review has become the standard process to assess artistic excellence and artistic merit. Several scholars and artists find that the peer-review process is flawed and hence it has been questioned by the lack of transparency. Hence, this dissertation provides more clarity of the peer-review process and opens the doors in an aim to unveils the process. I study three arts councils: The Canada Council for the Arts (CCA), the Ontario Arts Council (OAC), and the Toronto Arts Council (TAC). This study focuses on the adjudication of funding for the visual arts. In order to understand the complexity of the issues in the art world, I use a multi-disciplinary approach, drawing from education, social psychology, business, economics, and the arts. This study examines the dynamics of the decision-making process in the peer-review process and it is organized in three chapters that resulted in three independent papers that have been submitted for publication. Paper One, using discourse analysis, examines the definition of “artistic excellence” that is applied during the deliberation process. Paper Two studies government priorities that shape arts funding decisions. I draw from Pierre Bourdieu’s concept of Symbolic Power as the mechanism to analyze how government agencies exert influence on arts funding decision. Finally, in Paper Three, I focus on group decision-making. I draw from Irving Janis’ theory of Groupthink, a psychological phenomenon that occurs within a group of people, wherein the desire for conformity in the group results in an irrational or poor decision-making outcome. The three unique research papers explore the overall decision-making dynamic forces of arts councils in regards to peer-review processes and open new doors for the peer-review process because arts funding matters.
Architecture, Mapping Algorithms and Physical Design of Mesh-of-Functional-Units FPGA Overlays for Pipelined Execution of Data Flow Graphs
Keywords: Data Flow Graphs
FPGA
High-Performance
Overlay Architecture
Physical Design
Programming models

FPGAs can deliver high performance but their programmability wall hinders widespread use: they require hardware expertise and their CAD tools have long compile times. We tackle this challenge by exploring overlays: pre-compiled FPGA circuits that are themselves programmable via software-familiar models without FPGA CAD tools. We propose a high-performance mesh-of-functional-units overlay architecture that projects a model of pipelined execution of data flow graphs (DFGs). It consists of cells, each containing a functional unit (FU) and routing logic, with elastic pipelines and FIFOs in every routing hop. The architecture realizes latency insensitive data-driven execution, facilitates high Fmax and scales to large mesh sizes. We design a DFG-to-overlay mapping algorithm that places, routes, and balances DFGs on the overlay for high throughput. We also propose a bottom-up CAD flow based on partitioning and floorplanning of an overlay into tiles. The flow maintains high Fmax for large overlays and enables parallel compilation and quick stitching of tiles from a pre-compiled library. We prototype two overlays on a Stratix IV FPGA that has 212K ALMs: a 355 MHz 24x16 integer overlay and a 312 MHz 18x16 floating-point overlay. We map 16 DFGs and show that the two overlays deliver throughput of up to 37 GOPS and 22 GFLOPS, respectively. The DFG mapping is fast, taking less than 7 seconds. The tile-based bottom-up flow achieves 37% higher Fmax than the flat flow (the default CAD flow), with only 8% more resources. Compared to the flat flow, which compiles an overlay in 4 hours, the bottom-up flow stitches together an overlay from pre-compiled tiles in 35 minutes and can compile one from scratch in one hour, if tiles are compiled in parallel. The resource overhead of implementing the DFGs on the floating-point and integer overlays as opposed to compiling them directly to the FPGA averages to 4x and 9x, respectively. The compile time across the DFGs is reduced by 1500x. Our work demonstrates the feasibility of designing high-performance overlays that project a software-familiar programming model, scale with increasing FPGA resources and provide a considerable reduction in compile time. These benefits come with a modest resource overhead.
Synthesis, Reactivity and Photochemistry of π-Conjugated Tellurophenes
Keywords: conjugation
halogen photoelimination
oxidative addition
photochemistry
tellurophene

Organotellurium compounds undergo oxidation with halogens or other oxidants to form hypervalent adducts. This thesis presents studies on the redox chemistry of conjugated 2,5- disubstituted tellurophenes with a particular focus on light-driven reduction of the Te(IV) center. Functionalizing the tellurophene ring with conjugated substituents such as isoindigo allowed for visible light-driven reactivity (Chapter 2), and halogen photoelimination from tellurophene was demonstrated for the first time using green light. By replacing the isoindigo units with phenyl rings (Chapter 3), the bromine photoelimination quantum yields were improved by nearly 100- fold using blue light irradiation. Chlorine and fluorine photoelimination were also achieved. A series of substituted 2,5-diphenyltellurophenes was then studied to determine the effect of substituents on halogen photoelimination (Chapter 4). Quantum yields up to 42% were achieved for strongly electron-withdrawing 2,5-diphenyltellurophenes. Results from density functional theory calculations and laser flash photolysis experiments were used to propose mechanisms for halogen oxidative addition and photoelimination for the first time. These experiments also demonstrated that 2,5-diphenyltellurophenes are efficient singlet oxygen sensitizers. In chapter 5, the possibility of using conjugated tellurophenes as catalysts for aerobic oxidation reactions is explored. Telluroxides, which can be generated by reaction of tellurium-containing compounds with singlet oxygen, are efficient oxidants for various organic transformations. Since tellurophenes can generate singlet oxygen, a light-driven, self-sustaining catalytic cycle was envisioned where the Te(II) tellurophene both generates singlet oxygen and reacts with it to form the active Te(IV) telluroxide oxidant. The development of this catalytic system was unfortunately unsuccessful due to decomposition of the tellurophene by an oxidative ring-opening reaction. Based on the nature of the decomposition product formed in Chapter 5, an ene-dione, Chapter 6 explores whether derivatives of this structure could undergo ring-closing reactions with tellurium. Initial attempts to develop a synthetic route to conjugated 1,3-disubstituted benzo[c]tellurophenes have thus far been unsuccessful.
Deformation Behaviour of NiCo Multilayers with Modulated Microstructures
Keywords: deformation twinning
molecular dynamics
multilayers
nanocrystalline
physical metallurgy
work hardening

Metallic multilayers, which possess a material architecture of modulated coarse-grained and nanocrystalline features stacked in a laminate configuration, represent an ideal structure to study the influence of abrupt heterogeneities on deformation behaviour. While the deformation mechanisms of homogeneous coarse-grained and nanocrystalline materials are well documented, it is not clear from the current literature how these mechanisms may interact in a heterogeneous structure, and how these interactions manifest in the measured mechanical properties. The objective of this thesis is to characterize the dominant deformation mechanisms in NiCo multilayers with modulated microstructures. More specifically, a targeted study is performed to understand the influence of interfacial plastic interactions between multilayer features on the overall deformation behaviour. For this purpose, a wide range of multilayer architectures, which possess varying fractions of coarse-grained-nanocrystalline interfaces, are manufactured. The mechanical properties of these multilayers are measured using uniaxial tensile testing and nanoindentation, and the as-deposited structures are characterized through a combination of electron microscopy and crystallographic analysis. Interestingly, the flow stress of the multilayers is observed to significantly exceed rule of mixtures expectations as the fraction of structural interfaces is increased. These results indicate a strong contribution of interfacial effects to the overall deformation behaviour. Inspired by these findings, targeted molecular dynamics simulations are performed on representative architectures to investigate interfacial deformation mechanisms. Based on molecular dynamics simulations, a novel deformation mechanism, whereby strain relaxation is achieved in nanocrystalline features through emission of deformation twins into the coarse-grained microstructure, is elucidated. Consequently, the coarse-grained microstructure undergoes dynamic grain size refinement, leading to an increase in the intragranular boundary density. This deformation behaviour effectively reduces the dislocation mean free path of coarse-grained features, subsequently enabling additional strengthening. Based on the observed deformation mechanisms, a generalized phenomenological model is developed to predict multilayer work hardening, delivering significant improvements to rule of mixtures estimates. The emergence of deformation twinning in coarse-grained features is a unique consequence of microstructure modulation. This result offers a pathway to engineer deformation mechanisms and tailor mechanical performance through heterogeneous architectural design.
Neighbourhood Policymaking and Political Discourses of Exclusion, Risk and Effect: An Interpretive Policy Analysis of the Evolution of Place-Based Programs in the UK and Canada
Keywords: Critical social policy
Interpretive policy analysis
Neighbourhood effects
Organizational theory
Policy transfer
Social exclusion

The impact of various forms of neighbourhood change on the social fabric of metropolitan areas is a major concern throughout affluent Western nations. In addressing spatially-concentrated problems, urban policy-making and development patterns have become increasingly similar across the advanced capitalist countries. There is a transnational movement among policy-makers toward the application of geographically targeted, neighbourhood-based interventions referred to as area-based, or place-based policies. In cities across Western Europe, Australia, the United States, and Canada, we see the emergence of a new policy language: new policy frames, or storylines, which function to discursively construct the individuals and communities that reside in technocratically-defined ‘disadvantaged’, ‘priority’ or ‘at-risk’ neighbourhoods. Asking the question ‘why do certain ideas catch on in public policy’, this dissertation utilizes interpretive policy analysis (IPA) to understand how policy actors go about adopting transnational policy language, ideas and concepts – and how they enact them in their local contexts. This dissertation is focused on place-based policies and programs in the United Kingdom (UK) and Canada. Divided into three stand-alone papers, the dissertation explores three different but conceptually analogous topics. In doing so, it outlines the geographical and ideological origins of a place-based approach to local governance, and the means through which it has been established in local systems of governance. In the absence of scholarly research on ‘how, why, where and with what effects’ place-based policies have been circulated, learned, reformulated, and mobilized, this dissertation seeks to develop an understanding of the adaptations in the modalities and rhetoric of political actors, institutions and policy regimes which have accompanied the enactment of place-based policies at various scales of governance. IPA links ‘high’ politics (i.e., elite political institutions and multinational organizations) with ‘low’ politics (i.e., local and community-level governance). It orders and relates discursive elements (subjects, objects, tropes, narratives) to processes of meaning-making, representation and action. The IPA approach is used here to help account for the assemblage of policies, political discourses and regulatory tools that have produced new, place-based logics of 'social exclusion', 'risk' and 'neighbourhood effects' that are now widely understood as universal aspects of cities.