No description available.

No description available.

No description available.

No description available.

No description available.

Kubernetes is a fast emerging technological platform for developing and operating modern IT applications. The capacity to deploy new apps and change old ones at a faster rate with less chance of error is one of the key value proposition of the Kubernetes platform. A continuous integration and continuous deployment (CI/CD) pipeline is a crucial component of the technology. Such pipelines compile all updated code and do specific tests and may then automatically deploy the produced code artifacts to a running system. There is a thriving ecosystem of CI/CD tools. Tools can also be divided into two types: integrated and standalone. Integrated tools will be utilized for both pipeline phases, CI and CD. The standalone tools will be used just for one of the processes, which needs the usage of two independent programs to build up the pipeline. Some tools predate Kubernetes and may be converted to operate on Kubernetes, while others are new and designed specifically for usage with Kubernetes clusters. CD systems are classified as push-style (artifacts from outside the cluster are pushed into the cluster) or pull-style (CD tool running inside the cluster pulling built artifacts into the cluster). Pull- and push-style pipelines will have an impact on how cluster credentials are managed and if they ever need to leave the cluster. This thesis investigates the deployment time, fault tolerance, and access security of pipelines. Using a simple microservices application, a testing setup is created to measure the metrics of the pipelines. Drone, Argo Workflows, ArgoCD, and GoCD are the tools compared in this study. These tools are coupled to form various pipelines. The pipeline using Kubernetes-specific tools, Argo Workflows and ArgoCD, is the fastest, the pipeline with GoCD is somewhat slower, and the Drone pipeline is the slowest. The pipeline that used Argo Workflows and ArgoCD could also withstand failures. Theother pipelines that used Drone and GoCD were unable to recover and timed out. Pull pipelines handles the Kubernetes access differently to push pipelines as the Kubernetes cluster credentials does not have to leave the cluster, whereas push pipelines needs the cluster credentials in the external environment where the CD tool is running.

<p>Crohn’s Disease is a chronic inflammatory bowel disease characterized by an overzealous immune response to a microbial trigger in genetically susceptible individuals. Although this microbial trigger is unknown, <em>Escherichia coli</em> with adherent and invasive properties (Adherent-Invasive <em>Escherichia coli</em>, AIEC) is preferentially enriched in a proportion of Crohn’s Disease patients. AIEC can adhere to and invade intestinal epithelial cells and replicate intracellularly within epithelial cells and macrophages <em>in vitro</em>. One important colonization factor expressed by AIEC is the type 1 fimbrial adhesin protein FimH. FimH mediates colonization of CEABAC10 transgenic mice and can bind several host cell receptors including the macrophage receptor CD48 <em>in vitro</em> indicating a potential role for FimH in macrophage interaction. However, it was not known whether FimH contributed to phagocytosis of AIEC or colonization of wild-type mice. Here we show that FimH enhances early intracellular AIEC levels <em>in vitro</em> and colonization <em>in vivo</em>. We found that deletion of <em>fimH</em> may reduce intracellular AIEC burden at 2 hours post-infection and that this effect was modulated by bacteria opsonisation. Using a competitive index assay, we show that a Δ<em>fimH</em> mutant is unable to chronically colonize CD-1 mice at the same levels as the parental strain. Our results demonstrate that FimH is an important AIEC colonization factor and may increase interaction with macrophages. Identifying factors such as FimH which contribute to colonization and persistence will further our understanding of AIEC survival strategies within the host. Development of therapeutics targeting FimH may provide a means to reduce harmful bacteria overgrowth particularly after surgical intervention.</p> / Master of Science (MSc)

The tachykinin NK-3 receptor is a G-protein coupled receptor activated by mammalian tachykinin neuropeptides, which can modulate dopaminergic neurotransmission, and alter dopamine-mediated behaviors. The NK-3 receptor is currently under investigation as a novel therapeutic target for cocaine addiction. Our studies, as outlined in this dissertation, sought to determine if NK-3 receptors have a functional role in the acute as well as long-term behavioral effects of cocaine. Administration of NK-3 receptor agonists or antagonists potentiates or attenuates dopamine-mediated behaviors, respectively. Based on these findings, we hypothesized that blockade of neurokinin-3 receptors would alter acute and long-term behavioral responses to cocaine. We investigated whether acute and repeated administration of the NK-3 receptor antagonist SB 222200 altered hyperactivity induced by cocaine, and determined a possible mechanism involving dopamine D1 receptors in the striatum. We also determined whether NK-3 receptor blockade altered the development and expression of behavioral sensitization after repeated cocaine administration. Lastly, we investigated whether modulation of behavioral effects of acute and repeated cocaine by NK-3 receptors involved GSK3 phosphorylation in the nucleus accumbens. As described in this dissertation, we show that acute administration of the NK-3 receptor antagonist SB 222200 before a cocaine injection attenuated stereotypic responses produced by cocaine. Repeated administration of SB 222200 enhanced stereotypic activity produced by either cocaine or a low dose of SKF 82958 (0.125 mg/kg, i.p.) when administered seven days later. Dopamine receptor binding studies were performed to determine the mechanism of enhanced stereotypic responses. Binding studies showed a 19.7% increase in dopamine D1 receptor density in the striatum seven days later after repeated SB 222200 administration. These findings demonstrate that acute blockade of NK-3 receptors attenuated cocaine-induced behaviors in agreement with previous studies. Furthermore, these studies also show novel effects of repeated blockade of NK-3 receptors, which causes subsequent enhancement of cocaine and dopamine D1 receptor-mediated behaviors, possibly resulting from dopamine D1 receptor up-regulation in the striatum. In order to determine a role of NK-3 receptors in the development of cocaine-induced behavioral sensitization, the NK-3 receptor antagonist SB 222200 (2.5 or 5 mg/kg, s.c.) was administered prior to daily cocaine injections for 5 days. After a 7-day drug-free period, behavioral responses to a cocaine challenge were measured. Repeated administration of cocaine for 5 days induced a sensitized response upon a cocaine challenge 7 days later. Administration of SB 222200 prior to daily cocaine attenuated the development of behavioral sensitization. Moreover, administration of SB 222200 prior to the cocaine challenge blocked the expression of behavioral sensitization. These findings demonstrate that NK-3 receptor activity is involved in the development and expression of behavioral sensitization to cocaine. Lastly, we examined GSK3 phosphorylation in the nucleus accumbens induced by acute and repeated cocaine administration and determined if phosphorylation was altered by NK-3 receptor blockade. Similar to the drug administration regimens used in the behavioral studies, the NK-3 receptor antagonist SB 222200 was administered 30 mins prior to an acute cocaine injection. The nucleus accumbens was examined for changes in GSK3 phosphorylation by Western blot analysis. Increases in phosphorylation of the isoforms, GSK3α and GSK3β in the nucleus accumbens were detected 20 mins after an acute injection of cocaine. NK-3 receptor blockade prior to cocaine administration did not alter the cocaine-induced increase in GSK3 phosphorylation. Similar to the behavioral sensitization studies, SB 222200 was administered prior to repeated cocaine for 5 days, and 7 days later GSK3 phosphorylation was measured after a subsequent cocaine challenge. In contrast to the increases in GSK3α and GSK3β in the nucleus accumbens after an acute cocaine injection, no regulation of GSK3 phosphorylation was found after prior repeated cocaine administration and cocaine challenge. Administration of SB 222200 prior to repeated cocaine produced an increase in GSK3α and GSK3β phosphorylation after a cocaine challenge. Collectively, these data point to involvement of NK-3 receptor activity in changes in the phosphorylation of GSK3 in the nucleus accumbens produced by cocaine. In summary, functional involvement of NK-3 receptors in acute and long-term behavioral effects of cocaine was investigated. In agreement with previous findings, studies in this dissertation demonstrate that acute blockade of NK-3 receptors attenuates cocaine-induced behaviors. In addition, we found novel effects of repeated blockade of NK-3 receptors on cocaine-induced hyperactivity. There is enhancement of subsequent cocaine and dopamine D1 receptor-mediated behaviors possibly due to dopamine D1 receptor up-regulation in the striatum. NK-3 receptor activity was shown to be involved in long-term behavioral effects of cocaine and molecular changes in GSK3 phosphorylation in the nucleus accumbens. Blockade of NK-3 receptors prevented the development and expression of behavioral sensitization to cocaine and also blocked the changes in the phosphorylation of GSK3 in the nucleus accumbens. This dissertation has demonstrated a role of NK-3 receptors in modulating acute as well long-term cocaine-induced behavioral hyperactivity. Therefore, there is potential clinical relevance of NK-3 receptors in cocaine abuse and dependence as a therapeutic target for treatment, which warrants further characterization in future preclinical and clinical investigations. / Pharmacology

<p> In nuclear astrophysics, there are still undiscovered areas involving unstable nuclei, like the nucleosynthesis in exploding stars. The unstable nuclei are extremely difficult to produce in the laboratory for study since they decay away quickly once they are formed. To make the unstable nuclei available in the laboratory, Canada has built one of the best facilities in the world for nuclear astrophysics studies with radioactive beams, called TRIUMF-ISAC. Its recent upgrade to ISAC-2 can produce even heavier radioactive beams with higher energy. To fully utilize the ISAC-2 facility, a high-segmented HPGe γ-ray detector-TIGRESS, has been developed to study exotic nuclei using the well-established technique of Coulomb Excitation.</p> <p> As an essential part of the TIGRESS facility, auxiliary detectors, such as silicon detectors, are used to improve the sensitivity of the experiments through Doppler correction. Two types of silicon detectors will be used. One is the CD-shaped double-sided silicon strip detector, which is the topic of this thesis. The other one is the silicon barrel detector. This thesis will discuss the computer simulations and experimental tests of the CD detector.</p> <p> Simulations were made using a simulation toolkit GEANT4, which was run under the Linux system. The goal was to test the hypothesis that measurements of the energies of heavy ions in Coulomb excitation may improve the Doppler correction by constraining the scattering location in a thick target. To test the performance of the simulated CD detector, simple simulations were performed for shooting calibration alpha particles from an 241Am source first directly onto the CD and second through a thin target onto the CD. The goal of additional simulations was to attempt to determine the corresponding scattering depth in a thick target by putting an energy cut on the spectrum of the scattered beam detected in the CD. These simulation results verify the possibility of such localization, though the resolution is not very good.</p> <p> Experimental tests for the CD detector are aimed to obtain the energy resolution for each strip element of the CD and to have at least 8 channels instrumented in our test lab before this detector is sent to TIGRESS facility. The test station including electronics and detector systems and all results from initial tests are described in detail in this thesis.</p> / Thesis / Master of Science (MSc)

The adsorption behavior of silicic acid and arsenite alone and competitively on goethite over a broad pH range (3-11) at environmentally relevant concentrations was investigated utilizing pH adsorption data and zeta potential measurements. Both addition scenarios (Si before As(III) and As(III) before Si) were examined. The results of the adsorption experiments and zeta potential measurements were then used to model the single ion and competitive ion adsorption on goethite with the CD-MUSIC model implemented in the FITEQL 4.0 computer program. Silicic acid adsorption was reduced by the presence of arsenite for all but one of the adsorption scenarios examined, while in contrast silicic acid had little effect upon arsenite adsorption. However, the presence of silicic acid, regardless of the addition scenario, dramatically increased the arsenite equilibrium solution concentration over the entire pH range investigated. The CD-MUSIC model was able to predict the single ion adsorption behavior of silicic acid and arsenite on goethite. The modeled zeta potential data provided further evidence of the CD-MUSIC model's ability to describe the single anion adsorption on goethite. Our model was also able to collectively describe adsorption and zeta potential data for the low Si-arsenite adsorption scenario quite well however, our model under-predicted silicic acid adsorption for the high Si-arsenite competitive scenario. / Master of Science