VictorJuiz/thesis huggingface dataset:
Dietary Factors and Bone Health in Postmenopausal Women

Introduction: About 80% of those affected by osteoporosis are postmenopausal women. Therefore, identifying beneficial or harmful dietary factors for postmenopausal osteoporosis may have a significant public health impact. Objectives: The overall objective of this thesis was to examine the relations between various dietary factors and bone health in postmenopausal women aged ≥ 45 years using different analytical approaches. Methods: First, the associations between fruit and vegetables (F&V) intake and indicators of bone health were assessed using a systematic review approach. Electronic databases were searched and peer-reviewed observational and interventional studies published in English with F&V intake as a main dietary exposure were included. Data selection, extraction and evaluation of risk of bias were performed independently by two reviewers. Second, the associations between an overall diet quality index (HEI-2005) and its components with bone turnover markers (BTMs) were examined. Third, the relationships between alpha-tocopherol intake, serum alpha- and gamma-tocopherol, two concentration biomarkers of vitamin E intake, and their ratio and BTMs were assessed. For the second and third studies, cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were used. Weighted multiple regression models with adjustments for relevant confounders were used to examine the relationship between exposures and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-Telopeptides/Creatinine (uNTx/Cr), a biomarker of bone resorption. Results: There was significant between-study heterogeneity in design, definition and amount of F&V intake, outcomes, analyses and reporting of results in the eight included studies. Overall, cross-sectional and case-control analyses reported protective associations between F&V intake and bone health, whereas interventional and prospective cohort analyses did not. There were no associations between total HEI-2005 scores and BTMs. However, the Milk Group component of HEI-2005 had a significant inverse relationship with uNTx/Cr. Higher serum gamma-tocopherol and lower ratio of serum alpha- to gamma-tocopherol were associated with higher BAP concentrations but had no associations with NTx/Cr concentrations. Conclusions: The results confirm the existing knowledge that a diet with adequate intake of dairy may reduce bone loss. Further research is needed to examine the potential anabolic effects of gamma-tocopherol on bone in postmenopausal women.

Keywords: diet
bone health
nutrition
osteoporosis
postmenopausal women
vitamin E
diet Quality
fruit and vegetables
Advisor: Angela, Cheung
A Burl on the Living Tree: Freedom of Conscience in Section 2(a) of the Canadian Charter of Rights and Freedoms

The Charter grants to everyone, in s.2(a), the “fundamental …freedom of conscience and religion.” Yet the interaction between the two operative terms, “religion” and “conscience” remains largely unexplored. What, for example, is meant by “conscience”? By conscience in contradistinction to religion? Does s. 2(a) make a distinction between the state’s respect for religion and that of conscience? Can freedom of conscience be elevated to a freestanding right? Can conduct motivated by conscience be exempted from general laws in the way that some religious conduct has? Should the state take action to ensure conscience is protected? After more than 25 years of Charter commentary and jurisprudence, these remain deep questions, only partially answered. This project considers the possibility of building a case for an independent and robust “conscience” branch of s. 2(a), which will protect a broader range of freedoms, at the same time as allowing other disputes to be cast in more neutral tones (by taking them out of religious-based language, where possible) and allowing still others more room to develop in a more analytical and principled basis (as purely “religious” disputes more commonly associated with religious norms). In my view, there is, despite some opposition, sufficient justification in history, theory and doctrine to establish a separate and independent concept of freedom of conscience. At the same time, freedom of religion will always remain relevant as an acknowledgement of the distinct communal aspects of religion. Thus, a broad approach to freedom of conscience could include individual religious claims where the religious belief is based on a matter of conscience, and those conscience-based claims that lack a communal dimension, such as the prisoner who cannot eat meat or the whistleblower who feels compelled to report a supervisor. By exploring the origins of conscience and religious freedom, the basis behind the inclusion of conscience in many human rights documents, and the need for a theory that encompasses both as equal and complementary aspects of liberty, the dissertation sets out some possible ways in which freedom of conscience could be invoked and present a potential framework for assessing constitutional freedom of conscience claims.

Keywords: constitutional law
freedom of conscience
Advisor: Sossin, Lorne
Multidisciplinary Design Optimization of A Highly Flexible Aeroservoelastic Wing

A multidisciplinary design optimization framework is developed that integrates control system design with aerostructural design for a highly-deformable wing. The objective of this framework is to surpass the existing aircraft endurance limits through the use of an active load alleviation system designed concurrently with the rest of the aircraft. The novelty of this work is two fold. First, a unified dynamics framework is developed to represent the full six-degree-of-freedom rigid-body along with the structural dynamics. It allows for an integrated control design to account for both manoeuvrability (flying quality) and aeroelasticity criteria simultaneously. Secondly, by synthesizing the aircraft control system along with the structural sizing and aerodynamic shape design, the final design has the potential to exploit synergies among the three disciplines and yield higher performing aircraft. A co-rotational structural framework featuring Euler--Bernoulli beam elements is developed to capture the wing's nonlinear deformations under the effect of aerodynamic and inertial loadings. In this work, a three-dimensional aerodynamic panel code, capable of calculating both steady and unsteady loadings is used. Two different control methods, a model predictive controller (MPC) and a 2-DOF mixed-norm robust controller, are considered in this work to control a highly flexible aircraft. Both control techniques offer unique advantages that make them promising for controlling a highly flexible aircraft. The control system works towards executing time-dependent manoeuvres along with performing gust/manoeuvre load alleviation. The developed framework is investigated for demonstration in two design cases: one in which the control system simply worked towards achieving or maintaining a target altitude, and another where the control system is also performing load alleviation. The use of the active load alleviation system results in a significant improvement in the aircraft performance relative to the optimum result without load alleviation. The results show that the inclusion of control system discipline along with other disciplines at early stages of aircraft design improves aircraft performance. It is also shown that structural stresses due to gust excitations can be better controlled by the use of active structural control systems which can improve the fatigue life of the structure.

Keywords: Multidisciplinary Design Optimization
Aeroservoelasticity
Flexible Aircraft
Active Control
Advisor: Liu, Hugh
Martins, Joaquim R. R. A.
In Vitro and In Vivo Studies with Measles Virus and its Interaction with the Mouse Innate Immune System

Measles is one of the most contagious diseases known to mankind. Despite the availability of a safe and effective vaccine, approximately 164,000 measles-related deaths were recorded in 2008. The inherent restricted host tropism of MV means that the development of authentic rodent models will be a valuable research tool in testing new vaccines and antivirals. In addition to the receptor requirement, mouse innate immunity has been shown to inhibit MV growth. In this thesis, the contributions of several key components of the mouse innate immune system on the inhibition of MV replication were examined. The transcription factor interferon regulatory factor 3 (IRF3), which normally plays a key role in mediating innate immune signaling, contributed relatively little in inhibiting MV replication both in vitro and in vivo. In contrast, the JAK/STAT pathway and the double-stranded RNA inducible protein kinase, PKR, played more important roles in controlling virus replication. The resurgence of measles in areas where the virus was once thought to be eradicated makes the development of anti-MV treatments essential. Concurrent to the development of an animal model to better study its pathogenesis, we wanted to look at the effect of MV inhibitors on its replication. The MV fusion inhibitor, carbobenzoxy-D-phenylalanine-L-phenylalanine-glycine (ZfFG), was developed in the past to study fusion; however, its mechanism of action has not yet been elucidated. To examine this, spontaneous ZfFG-resistant mutants were generated and characterized. Mutations were found in the HRB region of the fusion (F) protein, and when these were modeled using published paramyxovirus F crystal structures, data suggested that ZfFG targeted a small pocket present between the head and stalk regions of its pre-fusion conformation. An authentic mouse model of measles developed from findings in this study may allow for in vivo efficacy testing of ZfFG in the future.

Keywords: molecular biology
virology
paramyxovirus
measles
innate immunity
mouse models
transgenic mouse
fusion
fusion inhibitor
FIP
IRF3
microbiology
ZfFG
plasmacytoid dendritic cell
mouse embryonic fibroblast
receptor
Advisor: Richardson, Christopher Donald
Coping with Crises: Christian – Jewish Relations in Catalonia and Aragon, 1380‐1391

This dissertation explores Christian-Jewish relations in the decades prior to the watershed of 1391, when Christian mobs throughout Castile and the Crown of Aragon killed or, more often, forcibly converted many Jews. My research indicates that the explosive violence of 1391 was not the predictable, inevitable result of growing interfaith animosity in the Crown of Aragon but was sparked by developments in Castile. Because of the resultant converso problem many historians consider 1391 to be a turning point in Iberian history. Yet historians have not closely explored Jewish-Christian interaction in the crucial later fourteenth century, particularly not in the Crown of Aragon, and have assumed, wrongly I believe, that the period following the Black Death (1348) saw a steady deterioration in the Jews’ relations with Christians. The first three chapters of the dissertation deal with the “crises” that marked late fourteenth-century Catalonia and Aragon. In the first chapter I outline the long-term precedents - the Black Death and successive wars – of the economic crisis that would follow. The second chapter focuses on economic matters – the Jewish contribution to the economy as well as the impact of growing debt and the development of new credit mechanisms. Chapter three, in turn, focuses on the impact of increasing taxation on Jewish communities. The final three chapters explore ways in which Jews and Christians coped with crises: chapter four deals with sources of conflict within Jewish communities, chapter five with conflict between Jews and Christians, while the last chapter looks at conversion as a way of coping with the crises of the fourteenth century. Throughout, my research shows how Jews and their Christian neighbours and rulers developed strategies and means of coping with the effects of epidemic disease, famine, and frequent warfare. I pay particular attention at how the law became a mechanism for coping with the worsening of economic conditions.

Keywords: Jews
relations
Spain
conversion
acculturation
legal culture
Advisor: Meyerson, Mark
Characterization of the SH2D5 Protein

The SH2D5 signaling molecule is a previously uncharacterized adaptor-like protein, containing an N-terminal phosphotyrosine binding (PTB) domain and a noncanonical Src Homology-2 (SH2) domain. With an antibody that I developed, I have shown that SH2D5 is highly enriched throughout adult brain regions. Furthermore, SH2D5 is localized to purkinjie cells in the cerebellum, the cornu ammonis (CA) of the hippocampus and pyramidal cells in the cortex. Despite harbouring two potential phosphotyrosine (pTyr) recognition domains, SH2D5 binds minimally to pTyr ligands. To discover the interaction partners of SH2D5 I conducted an immunoprecipitation/ mass spectrometry (IP/MS) screen from cultured Human Embryonic Kidney (HEK) 293T and Neuro2A cells along with murine brain lysates. These experiments revealed novel binding partners to SH2D5 including a prominent association with the RacGAP protein, Breakpoint Cluster Region protein (BCR), which is also highly expressed in brain. I have defined the interaction between SH2D5 and BCR and show that the PTB domain of SH2D5 engages an NxxF motif located within the N-terminal region of BCR. To address the biological significance of SH2D5, I utilized an siRNA approach to deplete the neuroblastoma cell-line, B35, of iii SH2D5. In these assays, B35 cells display a cell rounding phenotype and grow in a lattice formation. Furthermore, upon SH2D5 depletion these cells display low levels of activated Rac, associated with cell rounding. Taken together, these data reveal the first characterization of the SH2D5 signaling protein, its novel interaction with BCR and phenotype in neuronal-like cells. These data signify a biological function for SH2D5 in neurobiologic signaling perhaps applicable to learning and memory.

Keywords: protein signaling
neurobiology
Advisor: Pawson, Tony
Human Umbilical Cord Perivascular Cells: Putative Stromal Cells for Hepatocytes

Liver failure, which is the result of liver injury and pathological inflammation, is currently only successfully treated by organ transplantation. However donor organ shortages preclude transplantation for many patients in need. Thus, bioartificial liver systems (BALS) are being developed as a bridge to transplantation, or to create an environment conducive to liver regeneration. Hepatocytes, the main functional cells of the liver, are the cells of choice for BALSs, but in standard conditions ex vivo, they rapidly suffer from a reduction of their functionality and viability. Coculture with stromal cells, for example bone marrow mesenchymal stromal cells (BM-MSC), has been shown to improve, and extend, hepatocyte function ex vivo up to 21 days. But, only small numbers of BM-MSCs can be harvested from adult volunteers. We have previously described an alternative, more plentiful, source of MSCs — human umbilical cord perivascular cells (HUCPVC) — that are easily expanded and non-alloreactive. Our hypothesis was that HUCPVCs are putative stromal cells for hepatocytes. Our results show that HUCPVCs improved hepatocyte albumin secretion, urea synthesis and maintained hepatocyte cytochrome activity and the expression of hepato-specific genes. Furthermore, there was a net proliferation of hepatocytes, which were polarized in coculture with HUCPVCs, as judged by functional bile canaliculi that were present for up to 40 days. We found that both soluble and non-soluble factors contributed to these effects, while neither was able to allow net proliferation individually. Moreover, HUCPVCs expressed both hepato-trophic and anti-inflammatory factors, at different levels to BM-MSCs, indicating the potential for differential hepato-therapeutics. We conclude that HUCPVCs are putative stromal cells for hepatocytes; they improve hepatocyte functionality, polarity, morphology and net proliferation, and thus present an opportunity for the improvement of both BALS function and liver therapy.

Keywords: hepatocytes
mesenchymal
coculture
BALS
Advisor: Davies, John Edward
Beyond Affinity Propagation: Message Passing Algorithms for Clustering

Affinity propagation is an exemplar-based clustering method that takes as input similarities between data points. It outputs a set of data points that best represent the data (exemplars), and assignments of each non-exemplar point to its most appropriate exemplar, thereby partitioning the data set into clusters. The objective of affinity propagation is to maximize the sum of similarities between the data points and their exemplars. In this thesis, we develop several extensions of affinity propagation. The extensions provide clustering tools that go beyond the capabilities of the basic affinity propagation algorithm, and generalize it to various problems of interest in machine learning. We also investigate alternative approaches to the underlying mechanism of affinity propagation using recent inference techniques that are based on optimization theory. Affinity propagation was first described using a particular graphical model for the exemplar-based clustering problem. We first provide an alternative graphical model and derivation of affinity propagation, which are more amenable to model manipulation. Building on this representation, we develop capacitated affinity propagation, semi-supervised affinity propagation, and the hierarchical affinity propagation algorithms. We also discuss the relationship of affinity propagation to some canonical problems in combinatorial optimization. The underlying mechanism of affinity propagation is an approximate inference procedure known as max-product belief propagation. We provide a comparison of affinity propagation to alternative inference techniques such as max-product linear programming, and dual decomposition. We show that for a collection of benchmark data sets, affinity propagation outperforms these more theoretically justified approaches. We conclude by discussing the contributions and findings of this thesis, and how they relate to current research themes in more general inference problems. We point to several interesting avenues for future research.

Advisor: Frey, Brendan J.
Microorganisms and Metabolic Pathways Involved in Anaerobic Benzene Biodegradation under Nitrate-reducing Conditions

This thesis describes the characterization of benzene-degrading denitrifying cultures. Four objectives were pursued. The first objective was to identify conditions that promote or inhibit benzene decomposition and thus, to improve the biodegradation capacity of the cultures. FeS, resazurin, and nitrite had a detrimental impact on benzene degradation, whereas addition of supernatant from an active culture improved the benzene degradation activity by reducing the lag times. The second objective was to determine the microbial community composition in enrichment cultures and to identify the bacterial species that mediate benzene mineralization. Five dominant bacterial Operational Taxonomic Units (OTUs) were identified. The most abundant phylotype was related to the gram-positive Peptococcaceae family. Other bacteria present were closely affiliated with Dechloromonas, Azoarcus, Chlorobi and Anammox species. To correlate the growth of these specific microbes with benzene degradation, the abundance of specific 16S rRNA genes was monitored during mineralization process using quantitative polymerase chain reaction (qPCR). Based on the result of qPCR experiments and information about the metabolisms of the above bacteria, a syntrophic mode of benzene degradation was hypothesized to occur under denitrifying conditions. In this process, Peptococcaceae initiate attack on benzene, and ferment benzene to hydrogen and low molecular weight products such as acetate. These products are then consumed by nitrate-respiring Azoarcus and Dechloromonas or phototrophic Chlorobi. Anammox bacteria recycle and detoxify nitrite, and stabilize the culture. The third objective was to isolate and characterize pure cultures with the ability to mineralize benzene anaerobically. Dechloromonas- and Dechlorosoma-like microorganisms were isolated from several benzene-degrading microcosms. Theses bacteria, however, were not able to metabolize benzene anaerobically. The fourth objective was to investigate the key metabolic steps in the anaerobic benzene degradation pathway and to identify enzymes that are involved in this process. Differential transcription during growth of the culture on benzene versus growth on a metabolite of benzene degradation, i.e. benzoate was examined. Carboxylase-related genes were specifically transcribed in the presence of benzene. Furthermore, mRNA sequences corresponding to the genes that encode different enzymes of the benzoyl-CoA degradation pathway were present in the culture. These findings suggest that mineralization of benzene starts by its activation to benzoate through a carboxylation reaction catalyzed by benzene carboxylase. Benzoate is further metabolized through benzoyl-CoA pathway.

Keywords: Anaerobic benzene degradation
Benzene pathway
Advisor: Edwards, Elizabeth A.
Network Performance Analysis of Packet Scheduling Algorithms

Some of the applications in modern data networks are delay sensitive (e.g., video and voice). An end-to-end delay analysis is needed to estimate the required network resources of delay sensitive applications. The schedulers used in the network can impact the resulting delays to the applications. When multiple applications are multiplexed in a switch, a scheduler is used to determine the precedence of the arrivals from different applications. Computing the end-to-end delay and queue sizes in a network of schedulers is difficult and the existing solutions are limited to some special cases (e.g., specific type of traffic). The theory of Network Calculus employs the min-plus algebra to obtain performance bounds. Given an upper bound on the traffic arrival in any time interval and a lower bound on the available service (called the service curve) at a network element, upper bounds on the delay and queue size of the traffic in that network element can be obtained. An equivalent end-to-end service curve of a tandem of queues is the min-plus convolution of the service curves of all nodes along the path. A probabilistic end-to-end delay bound using network service curve scales with O(H logH) in the path length H. This improves the results of the conventional method of adding per-node delay bounds scaling with O(H^3). We have used and advanced Network Calculus for end-to-end delay analysis in a network of schedulers. We formulate a service curve description for a large class of schedulers which we call Delta-schedulers. We show that with this service curve, tight single node delay and backlog bounds can be achieved. In an end-to-end scenario, we formulate a new convolution theoii rem which considerably improves the end-to-end probabilistic delay bounds. We specify our probabilistic end-to-end delay and backlog bounds for exponentially bounded burstniess (EBB) traffic arrivals. We show that the end-to-end delay varies considerably by the type of schedulers along the path. Using these bounds, we also show that a if the number of flows increases, the queues inside a network can be analyzed in isolation and regardless of the network effect.

Keywords: Performance analysis
Scheduling analysis
Network calculus
End-to-end delay bounds
Advisor: Liebeherr, Jorg