VictorJuiz/thesis huggingface dataset:
Alterations in Transcription and Connectivity in Stem Cell-Derived Neurons of Children with Neurodevelopmental Disorders

Many neurodevelopmental disorders (NDD) have a genetic etiology. Some arise from mutations at a specific locus whereas others are polygenic. For example, Williams-Beuren Syndrome (WBS) is caused by hemizygous deletions at 7q11.23 that result in intellectual disability and increased socialization. In contrast, autism spectrum disorder (ASD) is common, results in impaired socialization, and has a polygenic, sex-dependent pattern of inheritance. While these NDDs involve genes in transcription and synapse function, it has been challenging to discover associated neuronal phenotypes owing to a lack of suitable human tissue. The recent development of human induced pluripotent stem cells (IPSC) allows to bridge this gap by providing a renewable source of neurons specific to individuals with NDDs. To examine transcription, I used IPSCs from a child with WBS and two children with ASD with mutations at the PTCHD1/PTCHD1AS locus, which encodes a protein and long non-coding RNA (lncRNA) of unknown function. In WBS neurons, I found an overall reduction in expression of synapse, voltage-gated potassium channel and extracellular matrix genes. In ASD neurons, I found a reduction in genes involved in RNA splicing, export, cellular respiration, and an increase in extracellular matrix genes. The large range of transcriptional alterations suggests that mechanisms of disease in these NDDs are complex and varied. To assess synaptic connectivity in ASD, I compared IPSC-derived neurons from two cases with mutations in SHANK2, a synaptic scaffolding gene, and engineered SHANK2 knockouts to parental and isogenic controls. Because heterogeneity among IPSC-derived neurons can compromise connectivity comparisons, I developed a Sparse coculture for Connectivity (SparCon) assay that increases statistical power by sparsely plating differentially labeled control and mutant neurons onto a lawn of unlabeled control neurons. Using SparCon, I found that dendrite complexity and total synapse number are increased in SHANK2 mutant cells, which was paralleled by increased excitatory synaptic activity. These findings are the first example of excitatory hyperconnectivity in IPSC-derived neurons from subjects with ASD and provide evidence that SHANK2 functions in early neuronal development as a suppressor of dendrite branching. In summary, IPSC-derived neurons are beginning to reveal transcriptional and synaptic neuronal phenotypes in vitro that are associated with NDDs. As the model system matures, methodological refinements like SparCon will further increase the ability of this system to discover disease phenotypes. Investigating alterations in transcription of synaptic genes in WBS, RNA splicing in PTCHD1/PTCHD1AS ASD, and hyperconnectivity in SHANK2 ASD will yield further insight into the pathophysiology of these NDDs.

Keywords: autism spectrum disorder
CRISPR
human neuron
induced pluripotent stem cell
SparCon
Williams-Beuren disorder
Advisor: Ellis, James
Studies of Atmospheric Ozone and Related Constituents in the Arctic and at Mid-latitudes

Two UV-visible differential absorption spectroscopy (DOAS) ground-based spectrometers (GBSs) were installed at the Polar Environment Atmospheric Research Laboratory (PEARL) in the Canadian High Arctic (80.1o N, 86.4o W). These two instruments have been used to measure stratospheric trace gases since 1999 and 2006 respectively. In 2010 and 2014, two solar-tracking systems were integrated with the GBSs to make tropospheric trace gas measurements. One goal of this work was to study surface ozone depletion events (ODEs) in the Arctic, using data from the GBSs. The measurements of ozone and BrO, combined with model results, indicate that both high wind/blowing snow and low wind/stable boundary layer are favorable environmental conditions for bromine explosion events, and in some cases, the combination of these two conditions will extend the lifetime of a bromine explosion event. In addition, during a strong surface ODE (ozone VMR

Keywords: Arctic
Bromine
MAX-DOAS
Ozone
profile retrieval
UV-visible spectroscopy
Advisor: Strong, Kimberly
Data Plane Traffic Engineering in Multimedia Communications using Software-Defined Networking

The quality of multimedia communications heavily relies on the condition of the end-to-end network. Sub-optimal resource allocation may deplete certain links sooner, making the network less resilient to link failures, traffic fluctuation or random traffic spikes. Regulating traffic can improve the media quality, but is not an easy operation to do in legacy IP networks. The maturing Software Defined Networking (SDN) technology provides the support for an unprecedented centralized solution in this regard: making it possible to deploy the optimal embedding of data flows via the central SDN controller. Thus the biggest challenge is to calculate such an optimal embedding for the data flows. This thesis presents our design of traffic engineering in multimedia communications which addresses to the resource allocation concerns in the data plane. Given the physical network, our objective is to allocate the network resource and embed the multimedia data flows in the way such that the total throughput is maximized. To achieve this, we introduce a Centralized Data Flow Routing Module into the control plane of the system. The Module employs a Two-Phase flow embedding procedure: Phase \RNum{1} is a global planning subroutine, periodically invoked. Given the traffic input of an extended time period, it produces and installs the optimal end-to-end tunnels between each pair of communication endpoints. Phase \RNum{2} is a Traffic Engineering (TE) subroutine, always active. It receives the individual data flow requests, and selects one of the pre-installed tunnels to embed the flow. For Phase \RNum{2}, first we propose a greedy-based TE algorithm. We investigate its performance and compare it with the performance if a Dijkstra-routing algorithm is employed. We show that the proposed heuristics outperform the Dijkstra's in three different metrics: session accept rate, maximum/average physical link utilization, and network criticality. In a second attempt, we present an incremental TE algorithm for Phase \RNum{2}. We numerically evaluate it and compare it with (\RNum{1}) Dijkstra algorithm and (\RNum{2}) the greedy-based TE heuristics. We show that the incremental TE excels in all three metrics: session accept rate, throughput, and link utilizations, under a wide spectrum of various network conditions and traffic conditions.

Keywords: Computer Networks
Multimedia Communications
Network Criticality
Software Defined Networking
Traffic Engineering
Advisor: Leon-Garcia, Alberto
Analysis and Design of Staircase Codes for High Bit-Rate Fibre-Optic Communication

Low-complexity, iterative hard-decision decoded staircase codes for hard-decision optical transport-networks (OTNs) are designed, with overheads (OH) between 6.25% and 33.3%. Extensive software simulations are performed for all code designs. Net coding gain gaps to hard-decision capacity are found to range from 0.45 dB at 6.25% OH to 1.38 dB at 33.3% OH. All code designs with

Keywords: coding theory
error correcting code
fiber-optical networks
graph theory
low-density parity-check codes
spatial coupling
Advisor: Kschischang, Frank R
Mobilizing for Distant Rebels: Weak Diasporas and the Mass Mobilization of Solidarity Activists

This dissertation examines the causes of grassroots organizing in support of distant rebel groups. In most discussions of this kind of transnational activism, scholars often focus on the mobilization of ethnic kin, or diasporas. By contrast, I focus on the mass mobilization of grassroots activists who have no ethnic tie to the distant rebels they support. I refer to these mobilizations as â mass solidarity mobilizations.â The emergence of these mobilizations is puzzling given not only that those who make them up often have weak historical, cultural and material ties to the distant rebels they support, but also that only some rebels but not others receive this kind of external assistance. Why do mass solidarity mobilizations form in support of some distant rebels but not others? This question matters since these mobilizations can shape distant intra-state conflicts by influencing third-party state policies and distant rebel resistance strategies. Contrary to most recent scholarship which focuses on how distant rebels frame their cause internationally and on international gatekeeper NGO advocacy, I focus on rebel recruitment strategies abroad. Drawing on more than 150 interviews with solidarity activists, a statistical analysis of an original dataset, and a comparative case of the grassroots solidarity organizing in North America and Europe for Palestinians and its absence for the Kurdish struggle in Turkey, I show that mass solidarity mobilizations are more likely to form for distant rebels that cannot rely on their ethnic kin abroad for meaningful support. In the absence of a strong external ethnic constituency, rebel activists are more likely to look beyond their ethnic kin and recruit non-diasporans instead. When they actively recruit non-diasporans, mass solidarity mobilizing on their behalf becomes more likely.

Advisor: Wong, Wendy
Single-Molecule Spectroscopy of Disordered States and Dynamics in Proteins

Single-molecule fluorescence techniques, such as Fรถrster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS), were applied to investigate the conformations, dynamics and interactions of disordered protein systems using custom-built confocal and total internal reflection microscopes. Conformational states of the N-terminal Src-homology-3 domain of downstream of receptor kinases (drkN SH3) were characterized. Both folded and unfolded states of drkN SH3 were detected under non-denaturing conditions. When exposed to high concentrations of urea and GdmCl denaturants, the protein still exhibits two distinct smFRET populations. We propose that the high-FRET population corresponds to denaturation-induced looped conformations. FRET experiments in formamide and DMSO suggest that interactions between hydrophobic amino-acid groups in the distal regions are involved in the formation of the looped state. To gain more insight into the determinants of unfolded protein structures, we studied an intrinsically disordered protein (IDP), the eukaryotic initiation factor 4E (eIF4E) binding protein 2 (4E-BP2). Nanosecond-scale dynamics was observed by FCS and was tentatively assigned to local peptide chain contact formation. Our data suggest that multi-site phosphorylation of the protein slows down the proximal chain motions and modulates the kinetics of distal regions. Segmental rotational correlation times and wobbling cone angles provided a rigidity map of the protein at different sites and were used to evaluate the binding mode to eIF4E. smFRET analysis reveals changes in the conformational ensemble responding to phosphorylation, denaturation, salt and pH. It is shown that both hydrophobic and electrostatic interactions play vital roles in determining the conformations of 4E-BP2. Encapsulating proteins into lipid vesicles has been widely used in studying their structural properties and the kinetics of protein-protein interactions. False signals will be introduced in these studies if the fluorescent probe itself interacts with the lipid wall. We employed the FCS method to systematically quantify the interaction between commonly used fluorophores and lipids and proposed mechanisms for the underlying interactions. This study offers a baseline correction for non-specific interactions and can be used to guide the pairing of dyes and lipids in the single-molecule fluorescence studies.

Keywords: Conformations
Dynamics
Fluororescence
Intrinsically disordered protein
Protein folding
Single molecule
Advisor: Gradinaru, Claudiu C
Exploratory High-Fidelity Aerostructural Optimization using an Efficient Monolithic Solution Method

This thesis is motivated by the desire to discover fuel efficient aircraft concepts through exploratory design. An optimization methodology based on tightly integrated high-fidelity aerostructural analysis is proposed, which has the flexibility, robustness, and efficiency to contribute to this goal. The present aerostructural optimization methodology uses an integrated geometry parameterization and mesh movement strategy, which was initially proposed for aerodynamic shape optimization. This integrated approach provides the optimizer with a large amount of geometric freedom for conducting exploratory design, while allowing for efficient and robust mesh movement in the presence of substantial shape changes. In extending this approach to aerostructural optimization, this thesis has addressed a number of important challenges. A structural mesh deformation strategy has been introduced to translate consistently the shape changes described by the geometry parameterization to the structural model. A three-field formulation of the discrete steady aerostructural residual couples the mesh movement equations with the three-dimensional Euler equations and a linear structural analysis. Gradients needed for optimization are computed with a three-field coupled adjoint approach. A number of investigations have been conducted to demonstrate the suitability and accuracy of the present methodology for use in aerostructural optimization involving substantial shape changes. Robustness and efficiency in the coupled solution algorithms is crucial to the success of an exploratory optimization. This thesis therefore also focuses on the design of an effective monolithic solution algorithm for the proposed methodology. This involves using a Newton-Krylov method for the aerostructural analysis and a preconditioned Krylov subspace method for the coupled adjoint solution. Several aspects of the monolithic solution method have been investigated. These include appropriate strategies for scaling and matrix-vector product evaluation, as well as block preconditioning techniques that preserve the modularity between subproblems. The monolithic solution method is applied to problems with varying degrees of fluid-structural coupling, as well as a wing span optimization study. The monolithic solution algorithm typically requires 20%-70% less computing time than its partitioned counterpart. This advantage increases with increasing wing flexibility. The performance of the monolithic solution method is also much less sensitive to the choice of the solution parameter.

Keywords: Aerostructural Optimization
Aircraft Design
Computational Fluid Dynamics
Coupled adjoint
Geometry Parameterization and Mesh Movement
Monolithic Solution Algorithm
Advisor: Zingg, David W
The Future of Canada's Medical Assistance in Dying (MAID) for the Mentally Ill and Physically Disabled

Canada's Medical Assistance in Dying (MAID) law continues to be a dividing issue. While it has been decided that only a few qualifying Canadians suffering from severe conditions may request assistance in dying, barriers currently in place may inevitably be lifted as legal challenges are brought against Bill C-14 for potential discrimination towards parties excluded from qualifying under the billâ s eligibility criteria. There is a potential of using the Charter as a force to expand assisted dying which may likely have negative implications on two of the most vulnerable groups in society, those living with a mental illness or physical disability. Studies on controversial practices emerging within the most liberal assisted dying regimes in Europe, Belgium and the Netherlands, may inform Canadian lawmakers on issues to avoid when possibly enacting a broader legalized practice in the near future.

Keywords: assisted dying
bill c-14
carter
euthanasia
health law
medical assistance in dying
Advisor: Lemmens, Trudo
Deeds, Gifts, and Executed Agreements: A Theory of Unilateral Transfer at Common Law

This thesis proposes to justify the place of the deed under seal within the common law of contracts. It argues that the effects of this particular device, at least in its more modern form, should not be understood by analogy to consideration-based contracts, but as the result of a unilateral transfer of rights analogous to the executed gift. Following the framework provided by Immanuel Kantâ s The Metaphysics of Morals, this second type of agreement arises simultaneously with, and is mediated through, the immediate transfer of particular rights from the deed-maker to the offeree. Accordingly, the enforceability of the deed is tied not to the nature of the promise made, but to the simultaneous performance of the underlying agreement.

Keywords: Contract
Deed
Gift
Promise
Seal
Transfer
Advisor: Benson, Peter
Parental Alienation in Quebec Custody Litigation

This thesis is a study of all Quebec custody cases dealing with parental alienation in 2016. It explores the definitions, findings, and implications of parental alienation in legal disputes, in light of the models of parental alienation and parental alienation syndrome described in the academic literature. This research confirms feminists’ skepticism towards the use of parental alienation in custody litigation. It concludes that alienation has varying and inconsistent definitions in law, that there is a considerable disconnect between the state of the research in science and judges’ knowledge on alienation, and that the concept of parental alienation in law is ambiguous and over-inclusive, seemingly to the detriment of mothers. There is a dire need for clearer and stricter guidelines on the use of parental alienation in Quebec jurisprudence to ensure its accuracy, coherence, and fairness. Cette thèse est une étude de toutes les décisions de garde d’enfant traitant d’aliénation parentale rendues au Québec en 2016. Elle explore les définitions, les raisonnements et les implications associées à l’aliénation parentale dans les litiges, à la lumière des modèles d’aliénation parentale et de syndrome d’aliénation parentale développés dans la littérature académique. Cette recherche confirme les préoccupations des féministes quant à l’utilisation du concept d’aliénation parentale dans les litiges sur la garde. Elle conclut que l’aliénation a des définitions variées et contradictoires en droit, qu’un fossé sépare l’état de la recherche en science et les connaissances des juges, et que le concept d’aliénation parentale en droit est ambigu et trop large, vraisemblablement au détriment des mères. Cette recherche conclut au besoin criant de lignes directrices claires et plus strictes relativement à l’utilisation de l’aliénation parentale dans la jurisprudence québécoise, afin d’en assurer l’exactitude, la cohérence et l’équité.

Keywords: custody
divorce
family
gender
law
parental alienation
Advisor: Shaffer, Martha
Whose Data? The Public Interest in Clinical Trial Information in Canada

Traditionally, the conception of clinical trial information has only recognized the commercial interest of the trial sponsor. This understanding has gradually shifted as the public interest in clinical trial information, which is grounded in the public contributions to the production of the information, has been recognized. The public interest is supported by the public health harms that can result when clinical trial information is kept confidential, and those public health harms reinforce the argument that the governmentâ s lack of transparency with respect to clinical trial information is an infringement of the freedom of expression and rights to life, liberty and security of the person. This paper will evaluate Health Canadaâ s current regime and argue that the public interest supports increased transparency of clinical trial information. It will also review the policies of the European Medicines Agency to demonstrate where there is room for improvement in the Canadian experience.

Advisor: Lemmens, Trudo
The Copyright- Design Conundrum: An Inquiry into the Efficacy of Sui Generis Design Laws

There exists a legal gulf separating copyright from industrial design in that these laws appear to be protecting different kinds of subject matter. While copyright law protects pure artistic works such as paintings and sculptures, design law purports to protect artistic works that are industrially applied to mass-produced goods. Copyright law refuses to protect designs that are applied to mass-produced goods and this is the line separating copyright from design. The normative assumption remains that a sui generis design law effectively protects all designs. This thesis aims to establish that in many cases copyright and design protect similar subject matter and, more importantly, challenges the notion that a piece of art must lose the status of a work, and the designer the status of an author merely because the artistic work has been industrially applied.

Advisor: Drassinower, Abraham
Memory Architecture Optimization for Streaming Applications in High-Level Synthesis

FPGA designs have an immense design space, and there can be an order of magnitude performance difference between a naive and an optimized implementation. To optimize memory, the programmer faces the burden of a large number of iterative manual optimizations to achieve high performance. Motivated by this challenge, the goal of this work is to make memory optimizations easier to achieve. We present two frameworks 1) a buffer-to-BRAM mapping tool called MPack, and 2) a library of Stream Memory Components (SMCs). MPack optimizes the mapping of application buffers to FPGAâ s on-chip physical memories (BRAMs). One of the key challenges is the mismatch between the dimensions (bit width and depth) of application buffers and FPGAâ s on-chip physical memories, which leads to low memory utilization. We automate the process of grouping buffers together and implementing them as a single memory. We use a simulated annealing-based algorithm that analyzes buffer dimensions and throughput and automatically generates a memory solution such that the throughput is maximized for a given BRAM budget. The SMC library contains three types of SMCs that implement data transformations, frequently implemented by programmers manually: 1) stencil, 2) transpose, and 3) tiling. The SMCs can be optimized through our custom library API. The SMC can be configured to stream data directly between OpenCL kernels, as well as off-chip memory. The SMC library provides fast design space exploration by allowing the user to specify a target BRAM budget for each SMC, and automatically maps SMC buffers to on and off-chip memory regions. We demonstrate that through the use of the MPack tool and the SMC library, the programmer can quickly generate a range of streaming application memory solutions, and reach performance targets without time consuming manual memory optimization.

Keywords: FPGA
HLS
memory optimization
stream applications
Advisor: Chow, Paul
The Compatibility of Human Rights Remedies with the Rule of Law: An Analysis of Rights Remedies in Canada and the United Kingdom, and Their Compatibility with the Rule of Law

This thesis analyses the development of human rights remedies in Canada and the United Kingdom in the context of two controversial rights issues, euthanasia and prisoner voting. It argues that the development of rights remedies in both jurisdictions has been done in a manner which is incompatible with the rule of law, and as such, creates the risk that individuals will be denied effective protection of their rights, either temporarily or permanently. It proposes a new framework for rights remedies, which ensures the immediate and effective correcting of rights violations, whilst providing a mechanism for engagement with the legislature, ensuring that the any judicial development of policy is constrained by legislative oversight, and ultimately subject to legislative amendment.

Keywords: Canadian Charter
Human Rights
Human Rights Act
Remedies
Rule of Law
Advisor: Roach, Kent