VictorJuiz/thesis huggingface dataset:
Principal's Instructional Leadership: Leading Capacity for Learning

Over the past decades, a body of literature on the instructional role of the principal has emerged (Hallinger , 1996). In our times of educational reforms and attempts at closing achievement gaps, the positive influence of the school principal as capacity builder has been gathering much interest (Bredeson, 2003; Davies, 2009; DuFour, 1991; DuFour, DuFour Eaker, 2008; Leithwood, K., Seashore-Lewis, Anderson, S. Wahlstrom, K., 2004;Venables, 2011). But if Liethwood et al. (2004) argue that the principal's influence on student achievement comes second only to the teacher's influence, much of how such influence is exerted within school communities remains to be uncovered. The conceptual framework from the study is inspired by Timperley and Alton-Lee's (2008) iterative cycle of teacher professional development, where teacher professional development is followed by changing teaching practices which in turn, is informed by student outcomes. The present conceptual framework has adapted the model to include the school principal. The purpose of this study was to gain a better understanding of the principal's leadership role as it pertains to the role's reality as a school capacity builder, asking the question: How do school principals influence the professional development of teachers to support teachers' instructional practices for student learning? The study attempted to answer the following three sub questions: 1) How do principals perceive their role in influencing the professional development of their teachers? 2) What are the strategies employed by principals to support teachers' professional development? 3) What are the barriers to supporting teachers' professional learning and growth that school leaders face daily? Semi-structured interviews were conducted with fourteen principals, 10 elementary and four secondary. All principals were from publicly-funded school boards in the province of Ontario, Canada. Main impediments to building school capacity include the principals' continuous struggle between administrative and leadership duties, the lack of autonomy in the planning of professional development, the lack of time for follow ups and the centralized nature of boards' professional development plans. Implications for policy, practice and future research are discussed.

Keywords: Development
Leadership
Principal
Professional
Advisor: Campbell, Carol
Regulation of Hippo Pathway Kinases MST1/2 by DLG5 and Other Signaling Factors

The Hippo signal transduction pathway plays critical roles in regulating development, organ size, and cancer progression, and is broadly conserved across metazoans. Mammalian Sterile 20-like Kinase 12 (MST1/2) are mammalian homologues of the Drosophila Hippo kinase, and along with downstream Large Tumor Suppressor Kinase 12 (LATS1/2), constitute the core kinases of the Hippo pathway. How MST1/2 are regulated, and in particular, what mechanisms connect them to upstream signaling components is a key question in the field. To address this, I employed affinity purification coupled to mass spectrometry to identify novel interacting proteins with important regulatory roles for MST1/2 and the Hippo pathway. I examined 25 different bait proteins related to the pathway, and identified 274 high confidence protein-protein interactions (PPI). The most intriguing PPI I identified was between MST1/2 and Discs Large Homolog 5 (DLG5), a widely conserved, large, multi-domain containing protein, which plays a role in maintenance of epithelial cell polarity. Using human, mouse, and fly model systems, fellow collaborators and I investigated the potential functional connections between DLG5, MST1/2, and other components of the Hippo pathway. We found that DLG5 acts as an inhibitor of Hippo signaling, in vivo and ex vivo. Mechanistically, I demonstrate that DLG5 binds directly to both MST1/2 and MAP/Microtubule Affinity-Regulating Kinase 3 (MARK3) and promotes their association. I found that MARK3 promotes hyperphosphorylation of MST1/2 and inhibits MST1/2 kinase activity. I propose a model wherein DLG5 recruits MARK3 to inhibit MST1/2 and the Hippo pathway. Although additional details of MARK3 regulation of MST1/2 await exploration, I have characterized DLG5 as a new and conserved component of the Hippo pathway and a negative regulator of MST1/2, providing the first example of a scaffold protein that directly links MST1/2 to other regulatory kinases and cell polarity factors.

Keywords: AP/MS
DLG5
Hippo pathway
MARK3
MST1
MST2
Advisor: Emili, Andrew
Technical Developments of in vivo Proton Magnetic Resonance Spectroscopy

Proton magnetic resonance spectroscopy (MRS) is a powerful non-invasive technique to probe the biochemistry of the brain and body. Because MRS signals are collected from metabolites in concentrations on the order of a few mM in biological tissues, (rather than from water at approximately 40 M concentration, as in magnetic resonance imaging) low signal-to-noise ratio (SNR) poses a major challenge. In the face of this challenge, there is an ongoing need for improved techniques to enhance the clinical applicability of MRS. One area of interest, for example, involves using MRS data as a biomarker for the assessment of early response in radiation therapy. This thesis focuses on the development of three MRS techniques, with the ultimate goal of this work being used in early radiation detection response protocols. First, a technique is developed to extend single voxel MRS to MRS of a small number of voxels (eg. two) without the need for spatial frequency encoding, using customized selective radiofrequency (RF) excitation and the localized sensitivity of multichannel receiver coils. The SNR efficiency of this technique is demonstrated in phantoms, healthy adult volunteers and patients with brain cancer. Second, a novel inversion and saturation recovery sequence is developed in conjunction with a spectral editing module to estimate the longitudinal relaxation time (T1) of lactate in vivo at 3 T. Lactate is of significant interest due to its role in cellular metabolism, and particularly its elevation in tumors. The resulting T1 estimate enables further optimization of MRS protocols and assists in estimating the absolute concentration of lactate from MRS data. Third, a diffusion-weighted two-dimensional spectroscopy sequence is developed, subsequently referred to as DW-JPRESS. This sequence, as well as an optimized processing pipeline, is demonstrated to provide estimates of the apparent diffusion coefficient (ADC) of brain metabolites beyond those typically accessible at 3 T, namely glutamate, myo-inositol and scyllo-inositol. The DW-JPRESS data provide unique information concerning the local diffusion environment of each measured metabolite, with the potential to characterize microstructural changes from different brain pathologies including cancer. Collectively, the technical development undertaken in this thesis promises to enhance future clinical applications of MRS, such as its use in distinguishing between neoplastic and nonneoplastic lesions, or for assessing tumor recurrence.

Keywords: Diffusion-weighted Spectroscopy
Magnetic Resonance Spectroscopy
Parallel Imaging
Relaxometry
Advisor: Graham, Simon J
Rhodium-Catalyzed Asymmetric Ring Opening of Oxabicyclic Alkenes and Palladium-Catalyzed Carbon-Halogen Bond Forming Reactions

Atom-economical addition reactions to unsaturated carbonâ carbon bonds represent a powerful class of transformations in organic chemistry, since a great deal of molecular complexity can be generated from simple starting materials. Highly regio- and stereoselective processes have been made possible through the use of transition metal catalysts, alongside specialized ancillary ligands and in combination with rational substrate design. One area of research in the Lautens group involves the transition metal catalyzed asymmetric ring opening (ARO) of strained alkenes, which provides access to enantioenriched carbocyclic frameworks. Although a variety of coupling partners have been applied in this transformation, the use of soft carbon nucleophiles remains limited in scope. The first chapter describes a rhodium(I)-catalyzed ARO of meso-oxabicyclic alkenes using silyl enol ethers and ketene acetals. In analogy to the Mukaiyama aldol reaction, a novel silyl migration occurs, enabling an in situ protection of the chiral alcohols obtained. Developing new reactivity from Heck-type carbopalladation processes represents another research interest in the Lautens group. Oxidative addition into a carbonâ halogen bond constitutes the first step of nearly all palladium(0)-catalyzed cross-couplings. Conversely, reductive elimination from palladium(II) to yield an organohalide product represents a rare and often thermodynamically unfavoured process. The next two chapters address challenges in the synthesis of vinyl halides using palladium(0) catalysis via the intramolecular carbohalogenation and chlorocarbamoylation of alkynes. During our investigations, we discovered that the steric bulk of both the substrate and the phosphine ligand play an important role in promoting the desired reactivity. Mechanistic insight has been gained through combined experimental and computational studies, which implicate a palladium-catalyzed stereoisomerization in both of these transformations. Under certain conditions, we demonstrate that highly stereoselective trans-additions to alkynes can be achieved, which illustrates that specific substrate/catalyst combinations can override the inherent cis-selectivity in carbometallations. In the fourth chapter, a formal palladium(II)-catalyzed alkyne chlorocarbamoylation reaction is presented, which provides access to medicinally relevant methylene oxindole scaffolds. In contrast to the analogous protocol using palladium(0) catalysts, the reaction is initiated by an alkyne chloropalladation step, followed by intramolecular cross-coupling with a carbamoyl chloride. Experimental and computational studies provide insight into the mechanism of this reaction.

Advisor: Lautens, Mark
Translation and Development of Molecular Imaging Probes for Detecting Response of Breast Cancer to Trastuzumab

The human epidermal growth factor receptor 2 (HER2) is overexpressed in up to 20% of breast cancers (BC) and confers an aggressive phenotype and a poor prognosis. Trastuzumab (Herceptin®) is a humanized anti-HER2 monoclonal antibody approved for immunotherapy of HER2-positive BC, however, many eligible patients do not derive benefit and better predictors of response are needed. SPECT/CT imaging with 111In-labeled pertuzumab has previously been shown to sensitively detect trastuzumab-mediated HER2 downregulation as a marker of response to trastuzumab therapy in HER2-overexpressing mouse xenografts. To advance this agent to the clinic, a kit for the preparation of 111In-BzDTPA-pertuzumab injection was developed under good manufacturing practices and tested against and consistently met quality specifications, including labeling efficiency, purity, sterility and endotoxins. Biodistribution, pharmacokinetic and radiation dosimetry studies of 111In-labeled pertuzumab in non-tumour bearing mice revealed no abnormal uptake in organs, slow elimination from the blood (t½β=228.2 h), and a projected total body radiation absorbed dose of 0.05 mSv/MBq. In an acute toxicity study of normal mice administered 23-times the planned clinical radioactivity dose (scaled), blood analyses revealed only slight changes in hemoglobin and serum creatinine levels; no differences in body weight between control and radiotracer injected groups, and no histopathological abnormalities of tissues were noted. A Phase I clinical trial was approved by Health Canada and initiated. A PET probe, 64Cu-NOTA-pertuzumab F(ab')2 was constructed to similarly detect HER2 changes in response to trastuzumab and was expected to have a lower radiation absorbed dose due to the faster elimination of F(ab')2 fragments and shorter half-life of 64Cu. The total body radiation absorbed dose projected for 64Cu-NOTA-pertuzumab F(ab')2 in humans was 0.015 mSv/MBq, a 3.3-fold reduction compared to 111In-BzDTPA-pertuzumab. PET/CT showed specific accumulation of 64Cu-NOTA-pertuzumab F(ab')2 in SK-OV-3 xenografted mice. Image analysis of mice treated with trastuzumab showed 2-fold reduced uptake of radioactivity in BT-474 xenografts injected with 64Cu-NOTA-pertuzumab F(ab')2 after 1 week of trastuzumab normalized to baseline, and 1.9-fold increased uptake in SK-OV-3 xenografts after 3 weeks of trastuzumab, consistent with tumour response and resistance, respectively. These results demonstrate that radiolabeled pertuzumab-based imaging probes are able to detect response to trastuzumab therapy.

Keywords: breast cancer
HER2
molecular imaging
monoclonal antibodies
nuclear medicine
translational research
Advisor: Reilly, Raymond M
Hybrid Exact Methods for Solving Strictly Convex Integer Quadratic Programs

The strictly convex integer quadratically constrained problem (IQCP) is an important class of optimization problem that arises in numerous applications both in theoretical science and industry. Due to its NP-hard nature, common exact methods are typically tree search algorithms with various techniques for pruning sub-trees while ensuring that at least one optimal solution is retained. In this dissertation, we exploit the similarities among three tree search algorithms, discrete ellipsoid-based search (DEBS), mixed integer programming (MIP), and constraint programming (CP) and integrate their techniques to develop efficient hybrid algorithms for solving IQCPs. We empirically demonstrate the superior performance of our hybrid algorithms in comparison to the previous best known exact methods in the literature. Our novel hybrid algorithms achieve the state-of-the-art on a variety of important classes of the IQCP, such as the binary quadratic programming problem, the exact quadratic knapsack problem, the variance minimization problem, and the integer least squares problems, which all have significant influence in the research fields of operations research (OR) and communications. In addition, we propose a novel global constraint in CP that infers domain reductions based on strictly convex quadratic constraints. Our new global constraint, together with the complementary branching heuristics, bring CP within an order of magnitude of the best-known techniques for the IQCPs tested, and achieve the state of the art when compared with general solvers such as CPLEX on some problem domains. Our new global constraint and branching heuristics fit naturally in the ``model and solve" framework of CP and provide much more flexibility than the hand-crafted, specialized algorithms, allowing practitioners to easily adapt our techniques. For the first time our study brings together the research of OR, CP and communications communities on IQCPs. We believe that our success in connecting different research fields can provide new insights into IQCPs and encourage future innovation.

Advisor: Beck, J. Christopher
Flow Fields and Particle Trajectories in Abrasive Slurry-jet Micro-machining of Sintered Ceramics and Metallic-layered Structures

The extreme hardness of sintered ceramics makes it difficult to machine them economically. Abrasive slurry-jet micro-machining (ASJM), in which a target is eroded by the impingement of a micro-jet of water containing fine abrasive particles, is a low-cost alternative for micro-machining of sintered ceramic materials without tool wear and thermal damage, and without the use of patterned masks. The experimental phase of the present research utilized several model systems that have industrial relevance while incorporating sufficient generality to illustrate generic characteristics of ASJM of ceramics and metallic-layered structures. Experiments were complemented by extensive computational slurry-flow modeling to understand the effects of the ASJM process parameters on the particle trajectories and the resulting erosion. In this study for the first time, computational fluid dynamic (CFD) modeling was used to derive a generalized relation between channel geometry and erosive flow, which was used in an existing numerical-empirical model to predict the cross-sectional profiles of ASJM micro-channels in sintered ceramics. The predictions agreed with experimental measurements to within about 8%. It was found that cavitation played a significant role in the slurry erosion of curved features such as the edges of holes and channels. Features with sharper edges, flat bottoms, and relatively steep sidewalls could be machined by minimizing cavitation through the use of liquids with low vapor pressure and relatively high viscosity. The use of ASJM to polish channels was investigated experimentally and with CFD. Post-blasting channels after their initial machining under typical process conditions reduced the Rrms roughness to about 23 nm in brittle and ductile targets. Flat micro-pockets in sintered ceramic substrates containing copper-filled through-holes were machined using a hybrid AJM (abrasive jet machining)-ASJM methodology, in which AJM was used to selectively erode the brittle ceramic without etching the ductile copper, followed by levelling of the protruding copper pillars to the depth of the ceramic using ASJM. It was demonstrated that electrodeposited copper and nickel-phosphorous layers could be selectively removed without eroding the underlying ceramic or metallic substrate using over-lapping ASJM channels. A CFD-aided process design methodology was developed to predict the ASJM parameters to remove a given coating thickness.

Keywords: abrasive
computational fluid dynamics
erosion
jet
micro-machining
slurry
Advisor: Spelt, Jan K
Papini, Marcello
Statistics of class groups and related topics

We prove several results concerning class groups of number fields and function fields. Firstly we compute all the moments of the p-torsion in the first step of a filtration of the class group defined by Gerth for cyclic number fields of degree p, unconditionally for p = 3 and under GRH in general. We show that it satisfies a distribution which Gerth conjectured as an extension of the Cohen-Lenstra-Martinet conjectures. In the p = 3 case this gives the distribution of the 3-torsion of the class group modulo the Galois invariant part. We follow the strategy used by Fouvry and Kluners in their proof of the distribution of the 4-torsion in quadratic fields. Secondly, we compute all the moments of a normalization of the function which counts unramified H8-extensions of quadratic number fields, where H8 is the quaternion group of order 8, and show that the values of this function determine a point mass distribution. Furthermore we propose a similar modification to the non-abelian Cohen-Lenstra heuristics for unramified G-extensions of quadratic fields for several other 2-groups G, which we conjecture will give finite moments which determine a distribution. These are all cases in which the unnormalized average is known or conjectured to be infinite. Our method additionally can be used to determine the asymptotics of the unnormalized counting function, which we also do for unramified H8-extensions. This part of the thesis is joint work with Brandon Alberts. Thirdly we present several new examples of reflection principles which apply to both class groups of number fields and picard groups of curves over P1/Fp. This proves a conjecture of Lemmermeyer about equality of 2-rank in subfields of A4, up to a constant not depending on the discriminant in the number field case, and exactly in the function field case. More generally we prove similar relations for subfields of a Galois extension with group G for the cases when G is S3, S4, A4, D2l and Z/ lZ × Z/rZ. The method of proof uses sheaf cohomology on 1-dimensional schemes, which reduces to Galois module computations.

Keywords: Arithmetic statistics
Class groups
Cohen-Lenstra heuristics
Number fields
Number theory
Advisor: Tsimerman, Jacob
Integrated Sources of Polarization Entangled Photon Pair States via Spontaneous Four-Wave Mixing in AlGaAs Waveguides

Polarization-entangled photon pair states (PESs) are indispensable in several quantum protocols that should be implemented in an integrated photonic circuit for realizing a practical quantum technology. Preparing such states in integrated waveguides is in fact a challenge due to polarization mode dispersion. Unlike other conventional ways that are plagued with complications in fabrication or in state generation, in this thesis, the scheme based on parallel spontaneous four-wave mixing processes of two polarization waveguide modes is thoroughly studied in theory and experimentation for the polarization entanglement generation. The scheme in fact needs the modal dispersion, contradictory to the general perception, as revealed by a full quantum mechanical framework. The proper modal dispersion balances the effects of temporal walk-off and state factorizability. The study also shows that the popular standard platform such as a silicon-on-insulator wafer is far from suitable to implement the proposed simple generation technique. Proven by the quantum state tomography, the technique produces a highly-entangled state with a maximum concurrence of 0.97 from AlGaAs waveguides. In addition, the devices directly generated Bell states with an observed fidelity of 0.92 without any post-generation compensating steps. Novel suspended device structures, including their components, are then investigated numerically and experimentally characterized in pursuit of finding the geometry with the optimal dispersion property. The 700 nmx1100 nm suspended rectangular waveguide is identified as the best geometry with a predicted maximum concurrence of 0.976 and a generation bandwidth of 3.3 THz. The suspended waveguide fabrication procedure adds about 15 dB/cm and 10 dB/cm of propagation loss to the TE and TM mode respectively, on top of the loss in corresponding full-cladding waveguides. Bridges, which structurally support the suspended waveguides, are optimized using the particle swarm algorithm to maximize the power transmission, and they were experimentally verified. This work greatly simplifies the generation of the PES and identifies a novel device structure suitable for such the PES generation. In combination with the reported promising advances in interferometric components and single photon detectors implemented in AlGaAs, the result of this thesis represents a step toward realizing a complete integrated quantum photonic circuit empowered by polarization-based protocols.

Keywords: Four-wave mixing
Integrated optics
Nonlinear optics
Quantum entanglement
Quantum optics
Advisor: Aitchison, J. Stewart