As customer demands become more stringent for canbody stock, it becomes essential to understand the complex interaction between the processing conditions and resulting product properties. This research focused on investigating the influence of homogenization process parameters (heat-up rate, soak temperature and time) on the microstructural evolution of an AA3104 aluminum alloy used for canbody stock. Experiments were conducted on samples taken from an industrial D.C. cast ingot and homogenized in a programmable temperature controlled laboratory furnace under various thermal profiles (i.e. homogenization temperatures 550°C, 580°C and 610°C at various heating rates and homogenization soak times of up to ten hours). The samples were then characterized in terms of their microstructure (retained manganese in solid solution, percentage a-phase, and size distribution and density of dispersoids). The homogenization process parameters were found to affect the evolving microstructure profoundly with: • An increase in heat-up rate favoring a reduction in the number of evolving dispersoids. • An increase in soak temperature increasing the Mn in solid solution, and decreasing the number of dispersoids that form. • An increase in soak time up to 3 hrs increasing the volume percent of α- Al₁₂(Fe,Mn)₃Si. Based on this work, a homogenization profile for optimum microstructure and texture development would include a fast heat-up rate to a high soak temperature (610°C) with moderate soak times (up to 3 hrs).

Appointment scheduling involves picking a strategy for sequencing patient appointments such that the wait time per patient is minimized and the idle time and overtime for the doctor are minimized. The goal of this project is to increase the number of scans per day at the echocardiogram clinic in the Hospital for Sick Children. The objectives were realized by performing simulations of the workflow of the echo clinic using simulation software. The simulation model did not precisely reflect the echo clinic, and the disparity was attributed to limitations in the simulation model. Nevertheless, the user accepted the model and six different policy change scenarios were explored. All six scenarios yielded significant increases in average scans per day per sonographer. Scenario IV, which eliminated the use of sonographer schedules, was recommended to be implemented due to ease of implementation and lack of negative effect on patient wait time and sonographer overtime.

Objectif: Examiner le lien entre la participation des parents aux activités physiques (AP) de leur enfant et les habitudes de vie et le statut pondéral de ces derniers. Méthode: Les données proviennent de l’Enquête Sociale et Santé des Enfants et des Adolescent Québécois (1999), comprenant des échantillons représentatifs de jeunes de 9, 13 et 16 ans (n=2511). L’implication des parents est définie par aucun, 1 seul, ou 2 parents faisant de l’AP avec leur enfant ≥1/semaine. Un rappel 7 jours a servi à classer les jeunes selon leur niveau d’AP, soit faible, modéré ou élevé. Le temps d’écran a été défini par: ≤14 vs. >14 heures/semaine. Le statut pondéral a été défini selon les critères de Cole. Résultats: Lorsque les deux parents participent aux AP du jeune, le niveau d’AP des adolescents de 13 (OR 3.89, IC 95%: 1.85-8.18) et 16 ans (OR 3.45, IC 95%: 1.32-9.01) est davantage élevé, et le temps d’écran moindre (OR 2.36, IC 95%: 1.30-4.25) chez ceux de 13 ans. Des analyses secondaires montrent que le lien entre l’implication des parents et le niveau d’AP des jeunes est présent chez les familles biparentales seulement; le lien avec le temps d’écran est présent dans les quartiers sécuritaires seulement. Aucune association n’est observée pour le statut pondéral. Conclusion: Les stratégies de promotion de la santé ciblant la participation des parents aux AP de leurs enfants pourraient réduire le fardeau des maladies chroniques, étant donné l’association favorable entre leur implication et les habitudes de vie des jeunes. / Objective: To examine the association between parental involvement in their child’s physical activity (PA) and child lifestyle behaviours and weight status. Methods: Data were from the 1999 Quebec Child and Adolescent Health and Social Survey, comprising representative samples of youth aged 9, 13, and 16 years. Parental involvement in PA with their child was assessed and measured as both, one, or neither parent engaging in PA with their child ≥once/week, based on parent reports. A 7-day PA recall was used to categorize youth as inactive, moderately-active, or highly-active. Screen time was classified as ≤14 and >14 hours of TV and video viewing/week. Overweight status was defined according to Cole’s sex- and age-specific BMI cut-points. Results: Participants (n=2511) with both parents engaging in PA with them ≥once/week (vs. neither parent) were more likely to be highly-active at ages 13 (OR 3.89, 95% CI: 1.85-8.18) and 16 (OR 3.45, 95% CI: 1.32-9.01), and to report ≤14 hours/week of screen time at age 13 (OR 2.36, 95% CI: 1.30-4.25). No associations were observed for weight status. We examined effect modification in post-hoc analyses; the association between parental involvement and youth PA was present in two-parent households only, while the association between parental involvement and screen time was only present in neighbourhoods perceived to be safe by parents. Conclusion: Health promotion strategies targeting parental involvement in youth PA may reduce the future burden of chronic disease, given the favorable association of parental involvement with several youth lifestyle behaviours.

Appointment scheduling involves picking a strategy for sequencing patient appointments such that the wait time per patient is minimized and the idle time and overtime for the doctor are minimized. The goal of this project is to increase the number of scans per day at the echocardiogram clinic in the Hospital for Sick Children. The objectives were realized by performing simulations of the workflow of the echo clinic using simulation software. The simulation model did not precisely reflect the echo clinic, and the disparity was attributed to limitations in the simulation model. Nevertheless, the user accepted the model and six different policy change scenarios were explored. All six scenarios yielded significant increases in average scans per day per sonographer. Scenario IV, which eliminated the use of sonographer schedules, was recommended to be implemented due to ease of implementation and lack of negative effect on patient wait time and sonographer overtime.

The identity of the source of the cosmic X-ray background (XRB) radiation above a few keV has been a mystery for the past 40 years. After the cosmic microwave background was found to have a spectral shape very close to that of a blackbody, it came to be accepted that some kind of discrete sources must produce the bulk of the X-ray background. However, by the mid-1990s, only about 30 per cent of this radiation had been resolved into discrete active galactic nuclei (AGN). The new generation of X-ray telescopes (<i>Chandra</i> and <i>XMM-Newton</i>) have now detected sources which possess the requisite flux and spectral shape to account for the bulk of the background at least up to 10 keV. This thesis presents several sets of observations and an XRB synthesis model, all of which aim to investigate the nature of the source populations which contribute a large fraction of the observed background flux and thus a large fraction of the Universal accretion energy density. An X-ray sample biased towards such sources is compiled from the fields of <i>Chandra</i> observations of galaxy clusters and powerful radio galaxies. These serendipitously-discovered sources cover the flux range ~ 10^-15- 10^-13 erg s^-1 cm^-2 [0.5-7 keV]. Starting with the field of Abell 2390, deep optical spectroscopy was carried out for a sample of these serendipitous sources. In this field itself, we find clear identifications of powerful and highly obscured AGN, at least one of which is a member of the class of 'type 2' quasars that should exist in the framework of AGN unification but have remained elusive so far. A sample of hard X-ray sources with weak optical fluxes in a number of fields is then compiled with the aim of discovering more such powerful, obscured sources. Near-infrared spectroscopy reveals a number of sources to have significantly featureless continua consistent with line emission being depleted due to large columns of intrinsic obscuring gas and associated dust. Near-infrared photometry is combined with medium-deep optical photometry to estimate photometric redshifts. The results are broadly consistent with targeted deep-field surveys which find a large fraction of obscured sources at moderate redshifts that are lower than previously predicted. The AGN we target are consistent with being hosted in massive galaxies at a large range of redshifts which peaks close to <i>z</i> = 1. We detect Iron reflection features in a few X-ray spectra. A new background synthesis model which successfully accounts for the recently updated observational constraints (including the areal number density of sources at faint fluxes and the peak of the observed redshift distribution) is then presented and predictions are made regarding observable features on the XRB spectrum. Concluding remarks draw together the results and discuss implications for AGN studies, including future work.

No description available.

Ligand-activated signal transduction is a process critical to cell survival and function as it serves as a means of communication between the cells and their environment. Endocytosis is generally thought to down-regulate incoming signals by reducing the surface availability of receptors. However, increasing evidence in many systems suggests a notion which is referred to as the „signalling endosome" hypothesis - that endocytosis can also actively contribute to signalling apart from clearance of activated receptors and thereby attenuation of signalling. The functional aspect of signalling endosomes has been well-characterized in several pathways including RTK and TGF-β signalling. There are, however, various other signalling pathways where the active mechanism of endocytotic regulation is yet to be understood. In this study, we probe this aspect in the cytokine signalling system, where the receptors are known to internalize but the significance of such internalization and precise mechanism is unclear. My thesis aims to elucidate the function and molecular details of internalization of cytokine receptor using interleukin-4 receptor (IL-4R) signalling as a model. IL-4 and IL-13 ligands can induce assembly of three distinct complexes: IL4 induced IL-4Rα – IL-2Rγ (type I), IL-4 induced IL-4Rα – IL-13Rα1 (type II) or the IL-13 induced IL-13Rα1-IL-4Rα (type II). The formation of any of these complexes triggers signalling through the JAK/STAT pathway. However, models of how the oligomerization of the transmembrane receptors and activation takes place are very diverse and lack a clear molecular and biophysical understanding of the underlying receptor dynamics. Previous results of the lab had shown that the affinities between subunits are low, precluding complex formation at the plasma membrane at physiological concentrations. In addition, IL-4R subunits localize in to endosomal structures adjacent to the plasma membrane. It had already been shown that the shared IL-4R subunit IL-2Rγ is internalized by a specific, actin dependent, Rac1/Pak1 regulated endocytosis route in the IL-2 context. We could show that pharmacological suppression of this endocytosis pathway also prevented IL-4 induced JAK/STAT signalling, placing endocytosis upstream of signalling. Here I show using immuno-EM techniques that these endosomal structures are multivesicular bodies. Importantly, I could show that receptor subunits are highly enriched in the limiting membrane of these endosomes relative to the adjacent plasma membrane. Using quantitative loading assays I could furthermore demonstrate that this enrichment is achieved by constitutive internalization of receptors from the cell surface into cortical endosomes. The trafficking kinetics of the receptor subunits is independent of ligand occupancy. Pharmacological inhibition shows that receptors and ligand traffic via the previously identified Rac1/Pak1 pathway. Finally, Vav2 was identified as a candidate Guanine Exchange Factor (GEF) that may regulate Rac1 activity and thereby control the actin polymerization cascade driving IL-4R endocytosis. Immunoprecipitations showed that Vav2 interacts both with the cytoplasmic tail region of the receptors and the receptor associated 2 kinase JAK3. Vav2 may thus couple the receptor/JAK complexes to the Rac1/Pak1 mediated endocytosis route. Taken together, our results suggests that stable „signalling endosomes‟ adjacent to the plasma membrane act as enrichment centres, where ligand and receptor concentrations are locally increased by constitutive trafficking. The confined environment of the endosome then compensates for the weak affinities between the ligand and receptor and facilitates ligand-mediated receptor dimerization. Importantly, overexpression of both type II IL-4R subunits renders signal transduction resistant to endocytosis inhibition, strongly suggesting that the critical factor effecting signalling is sufficient concentration, which the endosomes facilitate achieving. The endosomes are thus dispensable as signalling scaffolds when the receptors are in sufficient concentration, where activated receptors could interact with downstream pathway components. Endocytosis thus provides a crucial means for the signalling process to overcome the thermodynamic hurdles for receptor oligomerization. In conclusion, our data propose a novel, purely thermodynamic role of endosomes in regulating cytokine receptor signalling not seen in any other signalling pathway.

This thesis considers the tensile deformation characteristics of polypropylene fibre reinforced hardened cement paste having heterogeneous fibre geometries and a range of volume concentrations. Polypropylene fibres were prepared under various manufacturing conditions using a laboratory extruder, to ascertain the effect of these conditions on fibre characteristics. The relevant properties of cement paste likely to influence the polypropylene fibres and the eventual composite were investigated. An investigation of continuous aligned fibre composites in tension, containing various volume concentrations of fibres, showed that multiple cracking occurred despite the elastic modulus of the fibre being considerably lower than that of the hardened cement paste. Factors which enabled fibre/matrix contact to be maintained during the multiple cracking process, despite the unfavourable Poisson's ratio of polypropylene, were considered. Discontinuous aligned fibre composites were tested in tension, to ascertain the effect of volume concentration and length of fibres on the shear stress transfer between fibre and matrix and on multiple cracking. Composites containing parallel fibres, with fibre directions at varying angles to the direction of applied tensile stress, allowed an assessment to be made of the role of inclination. Crack distributions, pull-out behaviour of fibres and the ultimate stress of composites were investigated. Finally, random fibre reinforced composites were evaluated to provide a comparison with the Continuous, Discontinuous and Inclined fibre reinforced systems. In addition to determining the mechanical deformation of the various composites, the acoustic emission associated with internal deformation mechanisms was studied. This was undertaken with equipment capable of monitoring a range of acoustic pulse parameters.

Neurotransmitters play important roles in the early development of the mammalian central nervous system. Specifically, glutamate has been shown to mediate striatal neurogenesis via the ionotropic NMDA receptor. Here, it was investigated whether glutamate could exert an action on striatal neurogenesis by a metabotropic receptor mechanism in the developing rat. In vivo and in vitro methods were used to identify a role for the metabotropic glutamate receptor 5 (mGluR5) in striatal neurogenesis. mGluR5 glutamate receptor activation promotes neuroblast proliferation both in vivo and in vitro. The results of these experiments suggest that glutamate acting via the mGluR5 receptor plays an important novel role in striatal neurogenesis.

Methods of chemical hazard ranking and toxic impact assessment estimate fate and toxicity assuming the chemical exists in dissolved and particulate phases and, for metals, that all dissolved species are equally bioavailable. This treatment of metals, similar to organic chemicals, introduced a significant error in their estimates of hazard ranking since metal bioavailability and ecotoxicity are related to truly dissolved phase and specifically free metal ion within it. My thesis addressed this concern by developing a new method that introduced Bioavailability Factor (BF) to the calculation of Comparative Toxicity Potentials (CTPs) for hazard ranking of chemicals; also known as Characterization Factors for use in Life Cycle Impact Assessment (LCIA). First, the metal speciation/complexation was incorporated into fate calculations by loosely coupling commercial geochemical metal speciation model, WHAM, with a multimedia fate model, USEtoxTM, which is originally designed to calculate CTPs for organic chemicals. Second, Biotic Ligand Model (BLM) was used to calculate the bioavailability-corrected adverse toxic effects of metals. This new method was applied to assess the implications of choosing environmental characteristics, notably freshwater chemistry, by calculating BFs and CTPs of several cationic metals (e.g., Cd, Cu, Co, Pb, Ni and Zn) using 12 European, 24 Canadian ecoregions, several distinct freshwater-types selected from large river and lake systems world-wide. The newly estimated metal CTPs (i.e., ecotoxicity potentials) are up to ~1000 times lower than previous values used in LCIA. Notably the model results showed that the absolute values of CTPs, and their relative ranking amongst chemicals, are a product of the characteristics of a receiving environment. Hence it is crucial to select a generic freshwater archetype on which this analysis should be based. Finally, the new model framework was extended to apply within the Unit World Model (UWM) framework to estimate critical loads (CLs) of cationic metals to surface aquatic systems.