The Slit family (Slit1-3) of secreted glycoproteins and their cognate Roundabout family (Robo1-4) of transmembrane receptors provide important repulsive signals to guide cell migration during development and postnatal life. The dynamic regulation of Slit/Robo signaling is poorly understood in vertebrates. In this study, we identified a novel role for endocytosis in regulating Slit2 /Robo1 expression. Using heterologous expression systems, Slit2 was found be endocytosed in a Robo1-dependent manner and subsequently degraded in the lysosome, while Robo1 was found to be primarily recycled. An AP-2 consensus binding site, which mediates clathrin-dependent endocytosis, was identified in the Robo1 cytoplasmic tail and found to be required for Slit2 down-regulation and Slit2-induced endocytosis of Robo1. Preliminary data suggests that Slit2-induced endocytosis of Robo1 may be required for downstream signaling. These findings have important implications for how Slit/Robo signaling may be dynamically regulated during cell migration.

The Optical Spectrograph and InfraRed Imaging System (OSIRIS) satellite instrument spearheaded by a team of researchers at the University of Saskatchewan has provided scientists with 13 years of information about the state of the atmosphere. The success of the mission has motivated further development of the technology in a next generation instrument called the Canadian Atmospheric Tomography System (CATS) to provide better spatial and spectral resolution through a successive satellite mission. This work details the development of a proof-of-concept prototype built to test the validity of the CATS optical design. This thesis project utilized the developmental model built for the OSIRIS mission. The major modification made to the instrument replaced the optical element that defines the instrument’s field of view. This new development transformed the original single line of sight utilized by the satellite based OSIRIS instrument into three separate fields of view, which increased the imaging capabilities of the instrument. The new system has improved spatial resolution by collecting spectral information from three separate regions in the atmosphere in a single exposure, as opposed to the single region imaged by the original system. The newly developed prototype was tested on the platform of a stratospheric balloon. This test platform offered the capabilities to make limb scattered measurements similar to those that are made by a satellite based instrument. However, from the balloon geometry, the instrument required an additional pointing system to redirect the line of sight over stratospheric tangent altitudes. The design and test of this pointing system is also detailed in this work.

The development of remote sensing satellite-borne instrumentation for the study of the Earth’s atmosphere has provided an immense increase in our understanding of atmospheric trends and processes. The Canadian built OSIRIS satellite instrument uses the limb scatter technique to measure scattered sunlight for the retrieval of vertical profiles of atmospheric species such as ozone. Recently, the next generation instrument, CATS, based on the OSIRIS design, is under development to continue OSIRIS measurements into the future. One key optical design change for CATS is the ability to measure simultaneously over multiple fields of view. However, this new optical design concept needs to be tested and evaluated. To achieve this, a prototype slit plate was installed into the preflight developmental version of OSIRIS, called OSIRIS-DM, for testing in the laboratory and on a stratospheric balloon. In this thesis work, an evaluation of the performance of this multi-slit instrument was undertaken through laboratory calibrations and limb scatter measurement collection. The calibration process includes a wavelength registration, a spectral point spread function analysis, a relative calibration and an absolute calibration, all performed with laboratory equipment. Along with laboratory calibrations, this thesis work involved preparation for the stratospheric balloon mission including the development of a flight ready electronic control and communication system to operate OSIRIS-DM during the mission. The upgraded instrument was launched on September 19, 2014, and ascended to a stable float altitude of 36.5 km. The collected flight measurements were used to evaluate the calibrations and general instrument performance. Overall, the laboratory calibrations proved to be sufficiently accurate and the measurement collection produced multiple spectra that may be used for atmospheric analysis in the future. These results show that the multi-slit design of the slit plate produces an instrument that can be reliably calibrated and implemented for limb scatter measurement collection.

Plasmonics have been used to enhance the interaction of light with metallic nanostructures and lanthanide-doped upconversion nanocrystals. This enhancement can be achieved by using specific structures, materials, and plasmonic resonators at the emission and absorption wavelengths of the particles. This dissertation is based on four projects, which are mainly about the interaction of light and matter in metallic nanostructures and the up-conversion of nanocrystals using plasmonic resonators. In metal-insulator-metal systems, the cavity's resonant length is determined by the plasmon wavevector and the phase of reflection from the end faces. In general, the resonance length is not a simple multiple of the half-wavelength due to the significant reflection phase. As a result, in order to have a better understanding of MIM cavity resonances, the reflection phase must be calculated correctly. In the first project, the reflection phase obtained by SPPs upon reflection off the slit end-faces is calculated analytically using a simple mode matching model for real metals showing both dispersion and loss. The technique is similar to previous works, with the exception that we use the unconjugated version of the orthogonality relation. The results show good agreement with the experimental data. By having a strong grasp of the SPP dispersion, this technique aids in the design of plasmonic devices for operation at a specific wavelength. Single-photon sources are optical sources capable of emitting a single photon. A single lanthanide ion within a plasmonic nano structure with a large emission enhancement is one technique to generate a single-photon source at 1550 nm, which is a low-loss band used in fibre optics. In the second project, plasmonic double nanohole resonators are fabricated using colloidal lithography. These structures have been used to enhance the emission from low-concentration erbium emitters. The results indicate that different levels of emissions exist based on the amount of Er contained inside the nanocrystals. These findings would be an excellent starting point for developing a single-photon source operating at a 1550 nm wavelength employing erbium. Because not only can it increase the emission rate from erbium emitters, but it also helps to find and isolate a single emitter, which gives a stable single photon source. Because the surface plasmon resonance is exponentially coupled to the surface, it exhibits excellent sensitivity to changes in the refractive index near the surface. This is the underlying principle of commercially available surface plasmon resonance biosensors. Due to the wide range of applications in water quality testing and biosensing, it is critical to developing highly sensitive sensors that are compatible with commercial sensors. In the third project, we develop a design for SRSP sensing using a rectangular stripe grating and a 10 nm thick gold film. The 10 nm gold layer is sufficiently thick to enable continuous films to be formed using standard deposition procedures. We demonstrate that by employing rigorous coupled-wave analysis, the surface sensitivity of these films to an adlayer is increased by 3.3 times in angle units and the resolution is increased by fourfold while working at the commercial SPR system wavelength of 760 nm. Before trapping a particle in double nanohole apertures, we must first locate the double nanohole on the sample (gold on glass with apertures) and compare the scanning electron microscopy images with the image on the camera in the optical setup using certain markers. In the fourth project, to make DNH aperture trapping easier, we provide a polarization and transmission dependency approach for localizing and orienting DNHs on a substrate. This method provides a time and cost-effective way to ease the experimental process. This technique may also be used to localize different aperture clusters and single holes. / Graduate

Food allergy is a potentially life-threatening disease affecting up to 10% of individuals in Western countries. Clinical reactivity to food allergens is primarily mediated by immunoglobulin (Ig) E, with symptoms ranging from mild urticaria to anaphylaxis. Currently, food allergy remains a disease without a cure. Oral immunotherapy (OIT), which involves consuming small amounts of allergen, remains an experimental treatment in Canada, although has been approved by the Food and Drug Administration (FDA) in the United States for treatment of peanut allergy. While efficacious to induce desensitization, OIT is accompanied by a significant rate of adverse effects. Sublingual immunotherapy (SLIT) is a novel route of treatment for food allergy, where small amounts of allergen are placed under the tongue and held for 2-3 minutes. In contrast to OIT, SLIT offers not only treatment efficacy but also promises an excellent safety profile. The first objective of this thesis was to first develop a SLIT regimen in murine models of food allergy where sensitization is carried out either epicutaneously or intragastrically. Secondly, we investigated the efficacy of SLIT in modulating the clinical and humoral responses in prophylactic and semi-therapeutic settings. In the prophylactic setting, where SLIT was administered prior to sensitizing allergen exposures, SLIT-treated mice were completely protected from allergic sensitization including absent production of serum ovalbumin-specific IgE. In the semi-therapeutic setting, where SLIT was administered to mice primed to develop food allergy, it produced a partial protection against food-induced clinical reactivity. This was associated with lower levels of IgE production in comparison to non-treated, allergic mice. Together, this work provides both an optimized SLIT protocol, as well as evidence on the efficacy of SLIT in the treatment of food allergy in murine models. These findings will aid future work investigating the cellular and molecular mechanisms underlying SLIT-induced protection. / Thesis / Master of Science (MSc) / Food allergy is a potentially life-threatening disease which is primarily mediated by IgE antibodies. Strict allergen avoidance and use of rescue epinephrine upon accidental allergen exposure remain the standard of care. Oral immunotherapy, where individuals ingest small amounts of allergen, is currently the experimental treatment of reference to induce clinical tolerance; however, it is accompanied by a significant rate of adverse reactions. In contrast, sublingual immunotherapy (SLIT), which is less efficacious, upholds a superior safety profile. The primary objective of this thesis was to investigate the impact of SLIT in inducing clinical and immunological changes in murine models of food allergy. We demonstrated that when administered prophylactically, SLIT prevents mice from undergoing anaphylaxis. When administered to sensitized mice in a pre-allergic state, SLIT was protective against severe clinical reactivity after challenge. In conclusion, the work presented here establishes a useful platform to investigate the mechanisms underlying SLIT-mediated protection.

Разработка излучателя на основе волновода специальной формы. Щелевые волноводные излучатели находят широкое применение как в качестве элементов антенных решеток или облучателей апертурных антенн, так и в виде самостоятельных излучателей. Излучатели на основе прямоугольного волновода используется достаточно давно и их характеристики подробно исследованы. Но современные требования к антенным системам приводят к необходимым решениям ряда вопросов при использовании щелевых излучателей в волноводах специальной формы. В данной работе приведены результаты электродинамического расчета щелевых излучателей в некоторых разновидностях таких волноводов. / Development the radiator on the base of waveguide special form. Slotted waveguide radiators are used in construction for antennas elements arrays, irradiators reflector antennas, or for separate radiators. Radiators on the rectangular waveguide are explored many years ago. But modern requirements to antenna systems are leading to many questions, which we using slotted radiators in the waveguide special form. In this work you can see the results of electrodynamics calculation slotted radiators in some types of this waveguides.

No description available.

Para melhorar a visualização das pequenas estruturas anatômicas importantes para o diagnóstico do câncer de mama e otimizar o processamento das mamografias pelos sistemas computadorizados de auxílio ao diagnóstico (CAD), foi desenvolvido um dispositivo, baseado na tecnologia slit, que melhora a aquisição dos mamogramas. Este dispositivo reduz a radiação espalhada e o tamanho do foco e foi projetado a partir de um modelo computacional. O modelo adotado permite quantificar o valor desses parâmetros para qualquer sistema radiológico, qualquer espessura de tecidos moles radiografada e qualquer tensão aplicada ao tubo de raios-X. O dispositivo foi implementado e testado, quantificando as melhorias obtidas. As imagens geradas foram comparadas com as fornecidas pelos sistemas mamográficos convencionais. O modelo serviu para estudar também a interferência do espalhamento sobre o desempenho dos algoritmos usados nos sistemas de diagnóstico auxiliado por computador (CAD). / In order to improve the visualization of the small and important anatomical structures for breast cancer diagnosis and to optimize the image processing of mammograms by the computer aided diagnosis systems (CAD), a device that comes from slit technology was developed to improve the acquisition of mammograms. This device reduces the amount of scattered radiation and the focus size and it can be projected from a computational model. This model allows quantifying the value of those parameters, scattered radiation and the focus size, for any radiological system, any X-rayed soft tissue thickness and any tension applied to the X-ray tube. The device was implemented and tested quantifying the obtained improvements. The generated images were compared to the supplied for conventional mammography systems. The model was also good for studying interference on the algorithms used in the computer aided diagnosis systems (CAD).

No description available.

This study aimed to evaluate the clinical efficacy and systemic/mucosal antibody response changes after sublingual immunotherapy (SLIT) using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial extracts in mite-allergic children. One-hundred and two patients presenting allergic rhinitis with or without asthma were selected for a randomized double-blind, placebo-controlled trial and distributed into three groups: DPT (Dpt allergen extract, n=34), DPT+MRB (Dpt allergen plus mixed respiratory bacterial extracts, n=36), and Placebo (n=32). Clinical evaluation and immunological analyses were carried out before and after 12 and 18 months of treatment, including rhinitis/asthma symptom and medication scores, skin prick test (SPT) to Dpt extract, and measurements of Dpt, Der p 1, Der p 2 specific IgE, IgG4, and IgG1 in serum and specific IgA in saliva and nasal lavage fluid. Clinical results showed a significant decline in rhinitis/asthma symptom scores in all groups, but medication use decreased only in DPT group after 12 months. SPT results showed no significant changes and SLIT was generally safe, with no severe systemic reactions. SLIT using Dpt allergen alone induced increased serum IgG4 levels to Dpt, Der p 1 and Der p 2, and increased serum IgG1 and salivary IgA levels to Dpt and Der p 1. SLIT using DPT+MRB was able to decrease IgE levels to Der p 2, to increase salivary IgA levels to Der p 1, but had no changes on specific IgG4 and IgG1 levels. In conclusion, clinical improvement was observed both in the SLIT group and the control, but only active SLIT was able to modulate the mucosal/systemic antibody responses. These findings support the role of specific serum IgG4 and IgG1, in addition to salivary IgA, as probable blocking antibodies or biomarkers of tolerance that may be useful for monitoring the allergen specific immunotherapy. / Este estudo teve como objetivo avaliar a eficácia clínica e alterações da resposta de anticorpos sistêmicos e de mucosa após a imunoterapia sublingual (SLIT), utilizando alérgenos de Dermatophagoides pteronyssinus (Dpt), com ou sem extratos bacterianos em crianças alérgicas a ácaros. Cento e dois pacientes com rinite alérgica com ou sem asma foram selecionados para um estudo randomizado duplocego, controlado por placebo e distribuídos em três grupos: DPT (extrato alergênico de Dpt, n=34), DPT+MRB (extrato alergênico de Dpt associado com extrato de bactérias mistas do trato respiratório, n=36), e Placebo (n=32). Avaliação clínica e análises imunológicas foram realizadas antes do tratamento e após 12 e 18 meses, incluindo a pontuação de escores de sintomas e medicamentos de rinite/asma, teste cutâneo (SPT) ao extrato Dpt, e medidas de anticorpos específicos IgE, IgG4 e IgG1 para Dpt, Der p 1, Der p 2 no soro e IgA específicos na saliva e no lavado nasal. Os resultados clínicos mostraram uma redução significativa nos escores de sintomas de rinite/asma em todos os grupos, mas o uso de medicamentos diminuiu apenas no grupo DPT após 12 meses. Resultados de SPT não mostraram mudanças significativas e SLIT foi geralmente segura, sem reação sistêmica grave. SLIT usando somente alérgeno Dpt induziu aumento dos níveis de IgG4 para Dpt, Der p 1 e Der p 2 no soro, e aumentou os níveis de IgG1 no soro e salivares de IgA para Dpt e Der p 1. SLIT usando DPT+MRB foi capaz de diminuir os níveis de IgE para Der p 2, aumentar os níveis salivares de IgA para Der p 1, mas não tiveram alterações nos níveis de anticorpos específicos de IgG4 e IgG1. Em conclusão, foi observado melhora clínica tanto no grupo da SLIT como do controle, porém somente na SLIT com alérgeno foi capaz de modular as respostas de anticorpos sistêmicos e de mucosa. Estes achados reforçam o papel de anticorpos IgG4 e IgG1 séricos específicos, além de IgA salivar, como prováveis anticorpos bloqueadores ou biomarcadores de tolerância que podem ser úteis para monitoramento da imunoterapia alérgeno-específica. / Doutor em Imunologia e Parasitologia Aplicadas