Alzheimer’s disease (AD) patients could benefit from a more effective treatment than the current FDA-approved options. Because amyloid-beta (Aβ) is thought to play a central role in AD pathogenesis, many experimental drugs attempt to reduce Aβ-induced pathology. Preventing amyloid accumulation may be a more effective strategy than clearing Aβ plaques after they form. If preventing Aβ accumulation can treat or prevent AD, then understanding Aβ primary nucleation may aid rational drug design. This study examines Aβ residue interaction networks and reports network and structural observations that may provide insight into primary nucleation. While many studies identify structural features of Aβ that promote aggregation, this study reports features that may resist primary nucleation by examining Aβ42 studies in more and less polar solvents. In Aβ42 in a less polar solvent (PDB ID: 1IYT), Val24 and Ile31 have higher betweenness and residue centrality values. This may be due to a predicted interaction between Val24 and Ile31. Residues in the central hydrophobic cluster (CHC) of Aβ40 and Aβ42 had significantly higher betweenness values compared to the average betweenness of the structures, highlighting the CHC’s reported role in oligomerization. The predicted interaction between Val24 and Ile31 may reduce the likelihood of primary nucleation of Aβ.

In optical disk systems, a semiconductor laser is used to read out the data recorded on the disc. Since the laser is the first noise source, there are strictly rated values for laser's noise in various optical disk systems to ensure the normal operation of the system. Among different laser noises, the worst one is the optical feedback noise. The feedback light will disturb the longitudinal modes of the laser and induce huge fluctuation in Laser's output. In our work, we study the effect of optical feedback on Laser's modes and relative intensity noises under various driving current and chop temperature. We try to find out methods that can suppress the Laser's noise and try to give some suggestions for the design of disc driven. Some experiments about a commercialized optical disk driver are also reported as well.

Traumatic brain injury (TBI) is a progressive disorder, in which the primary injury results in the initiation of a complex cascade of secondary biochemical and metabolic changes resulting in lasting neurological dysfunction and cognitive impairment. The heterogeneous nature of the disease has complicated the development of pharmacological agents to improve the outcomes of TBI; to date, no therapeutic treatment has been shown to be effective in clinical trials. Treatments targeting multiple secondary outcomes (cell death, axonal degeneration, and inflammation) may provide enhanced therapeutic efficacy following TBI. Small Ras family GTP-binding proteins govern diverse cellular processes by directing the relay of extracellular stimuli to the activation of select intracellular signaling pathways. Rin (RIT2) is a member of the Rit subfamily of Ras-related family of GTPases, and is expressed solely within neurons of the CNS. Early cell culture models demonstrated that Rin signaled upstream of the stress-activated protein kinase, p38, and lacked the transformative abilities displayed by other members of the Ras family, suggesting functions for Rin other than cell growth and proliferation. To begin to define the physiological function of Rin, we generated a RIT2 knockout mouse and examined the impact of Rin loss in the CNS following brain trauma. Our data demonstrates that Rin deficiency is neuroprotective following a controlled cortical impact (CCI) injury, reducing both acute hippocampal neurodegeneration and promoting sustained neuronal survival, without affecting post-CCI neurogenesis. Hippocampal neuroprotection achieved by Rin loss was accompanied by improved cognitive function in injured mice. Furthermore, we demonstrated that Rin loss led to blunting of axonal degeneration and microglial activation in the optic nerve following optic nerve stretch injury. The molecular interaction between Rin and dual leucine zipper kinase suggested a potential role for Rin in the regulation of a novel stress MAPK-dependent neuronal death cascade. Lastly, we demonstrated through diffuse closed head injury, that Rin loss mitigates cytokine release as a result of injury without altering glial activation. Together, these studies establish Rin as a novel regulator of neuronal cell death, cognitive decline, axonal degeneration, and cytokine production following traumatic brain injury.

Les interconnections optiques dans les fermes de données (data centers) nécessitent la mise au point de nouvelles approches technologiques pour répondre aux besoins grandissants en composants d’interface respectant des cahiers de charge drastiques en termes de débit, coût, encombrement et dissipation d’énergie. Les peignes de fréquences optiques sont particulièrement adaptés comme nouvelles sources optiques, à mêmes de générer un grand nombre de porteuses optiques cohérentes. Leur utilisation dans des systèmes de transmission en multiplexage de longueurs d’onde (WDM) et exploitant de nouveaux formats de modulation, peut aboutir à des capacités jamais atteintes auparavant. Ce travail de thèse s’inscrit dans le cadre du projet européen BIG PIPES (Broadband Integrated and Green Photonic Interconnects for High-Performance Computing and Enterprise Systems) et a pour but l’étude de peignes de fréquences générés à l’aide de lasers à verrouillage de modes, à section unique, à base de bâtonnets quantiques InAs/InP et puits quantiques InGaAsP/InP. Nous avons entrepris l’étude de nouvelles couches actives et conceptions de cavités lasers en vue de répondre au cahier des charges du projet européen. Une étude systématique du bruit d’amplitude et de phase de ces sources a en particulier été menée à l’aide de nouvelles techniques de mesure afin d’évaluer leur compatibilité dans des systèmes de transmission à très haut débit. Ces peignes de fréquences optiques ont été utilisées avec succès dans des expériences de transmission sur fibre optique avec des débits records dépassant le Tbit/s par puce et une dissipation raisonnable d’énergie par bit, montrant leur fort potentiel pour les applications d’interconnections optiques dans les fermes de données / The increasing demand for high capacity, low cost, high compact and energy efficient optical transceivers for data center interconnects requires new technological solutions. In terms of transmitters, optical frequency combs generating a large number of phase coherent optical carriers are attractive solutions for next generation datacenter interconnects, and along with wavelength division multiplexing and advanced modulation formats can demonstrate unprecedented transmission capacities. In the framework of European project BIG PIPES (Broadband Integrated and Green Photonic Interconnects for High-Performance Computing and Enterprise Systems), this thesis investigates the generation of optical frequency combs using single-section mode-locked lasers based on InAs/InP Quantum-Dash and InGaAsP/InP Quantum-Well semiconductor nanostructures. These novel light sources, based on new active layer structures and cavity designs are extensively analyzed to meet the requirements of the project. Comprehensive investigation of amplitude and phase noise of these optical frequency comb sources is performed with advanced measurement techniques, to evaluate the feasibility of their use in high data rate transmission systems. Record Multi-Terabit per second per chip capacities and reasonably low energy per bit consumption are readily demonstrated, making them well suited for next generation datacenter interconnects

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Le développement de sources lasers monomodes et accordables constitue un enjeu important dans plusieurs domaines en fort développement telle que la métrologie, les senseurs optiques, la spectroscopie, le traitement optique de l'information ou la médecine. Dans cette thèse nous faisons le point sur les limites des technologies actuelles, puis nous montrons comment les surpasser à travers la conception et l'étude physique de lasers à semiconducteur de haute cohérence émettant dans l'infrarouge. Nous nous intéressons particulièrement aux VECSEL dans le but d'obtenir un fonctionnement monofréquence accordables et robustes. Nous traitons de la conception et de la caractérisation de ces lasers, depuis l'optimisation du milieu à gain jusqu'à l'élaboration de prototypes laser fonctionnels. Nous effectuons ensuite une étude approfondie des propriétés physiques de la source. Les différents sujets abordés traitent de nombreux aspects de l'optoélectronique tels que la physique du solide, l'optique traditionnelle et quantique, la technologie des matériaux, la thermique, ect. Les travaux présentés ici ouvrent la voie à de nombreux développements liés aux VECSEL et à leurs applications.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Thesis (Ph. D.)--University of Wisconsin--Madison, 1980. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 543-548).

>Magister Scientiae - MSc / The plant Hypoxis hemerocallidea, also known as the African potato, is commonly used as a traditional medicine to treat diabetes in South Africa. The mechanism by which it lowers blood glucose levels is not known. The main aim of this research was to study the possible hypoglycemic effect of HH using RIN-5 F pancreatic tumor cells. To accomplish this, the study was divided into three parts: (1) to test whether exposure of RIN-5F cells to glucose and HH extract affect the cell proliferation and cell viability, (2) to test whether the HH extract have an effect on insulin secretion, and (3) to test whether the HH extract has an effect on alpha amylase and alpha glucosiadase enzyme activity. The RIN-5F cells were exposed to different concentrations of glucose (5, 10, 20, 37.5, 50, 55, 74, and 92.3 mM) for different times (1, 3, 6 and 24 hours). The RIN-5F cells were also exposed to different concentrations of HH (50, 100, 150, 200 and 500 μ/ml) for different times (1, 3, 6 and 24 hours). Cell proliferation was evaluated using crystal violet staining and cell viability was evaluated using the XTT assay. To evaluate the effect of glucose and HH on RIN-5 F cell insulin secretion the cells were exposed to HH (100 μg/ml or 500 μg/ml) and / or glucose (2 mM or 50 mM) for 30 or 90 minutes. Insulin, α-amylase activity and α-glucosidase activity were evaluated by using commercially available colorimetric assays. Enzymatic activity in the presence of HH was compared with positive controls for α-amylase activity or α-glucosidase activity. Results are expressed as means ± SEM or median. Statistical differences among groups were analyzed by analyses of variance. P < 0.05 was considered as significant. An increase in the cell viability and cell proliferation was found when RIN-5 F cells were exposed to high glucose concentrations and a high dose of HH extract for a short time period (1, 3 and 6 hours). When the cells were exposed to the HH extract over 24 hours, HH did not affect cell viability significantly. Insulin secretion from RIN-5 F cells was increased when exposed to low glucose (2 mM) or high glucose (50 mM) for 30 minutes. Insulin secretion was increased from RIN5F cells after exposure to low HH (100 μg/ml) or high HH (500 μg/ml) for 30 minutes. Exposure of RIN5-F cells to HH for 90 minutes caused a further increase in insulin secretion from (4.3±0.17 mIU/mg protein; P ≤ 0.01) in 100 μg/ml, to (7.87±0.17 mIU/mg protein; P ≤ 0.001) in 500 μg/ml. At both 30 minutes and 90 minutes, insulin secretion was significantly higher when cells where exposed to 500 μg/ml HH compared to 100 μg/ml HH. Insulin secretion by cells exposed to 2 mM glucose + 100 μg/ml HH (4.69±0.16 mIU/mg protein; P ≤ 0.001) was significantly higher than when exposed to 2 mM glucose only (2.27±0.17 mIU/mg protein), while the insulin secretion in 2 mM glucose + 500 μg/ml HH (2.56±0.17 mIU/mg protein; P > 0.05) was not significantly different from that in 2 mM glucose treated cells (2.27±0.17 mIU/mg protein). Similar results are obtained after 90 minutes. In the presence of high-glucose (50 mM), at both 30 minutes and 90 minutes, insulin secretion was significantly decreased when cells where exposed to low concentration of HH (100 μg/ml) and high concentration of HH (500 μg/ml). The HH extract produced α-amylase enzyme inhibition. The maximum inhibition was at a concentration of 10μg/ml (922±117U/ml; P ≤ 0.01). The 5 μg/ml concentrations failed to produce significant inhibition. The HH extract had significant α- glucosidase inhibitory activity at a concentration of 5μg/ml (0.12±0.3U/ml; P ≤ 0.001) or 10μg/ml (0.13±0.3U/ml; P ≤ 0.001). In conclusion, based on its ability to inhibit α-amylase and α- glucosidase activity HH has the potential to be used in control of blood glucose levels. The HH aqueous extract increased insulin secretion under our basic experimental conditions and in the presence of low glucose levels, but not at high (50 mM) glucose concentrations. Insulin secretion in the presence of different glucose concentrations, in the presence of HH, needs further investigation. It is recommended that the ability of HH to stimulate insulin secretion be evaluated at 15-20 mM glucose.

U rgyan pa Rin chen dpal (1230-1309) was a great adept of the bKa' brgyud school of Tibetan Buddhism, particularly renowned for his knowledge of the Kālacakra tantra and the unique teaching known as the Approach and Attainment of the Three Vajras (rDo rje gsum gyi bsnyen sgrub), said to have been given to him in his vision by Vajrayoginī (rDo rje rnal 'byor ma) in the Miraculous Land (sprul pa'i zhing) of U rgyan. He was the student of the 2nd Karma pa, who entrusted him with the Black Hat, which he passed to the 3rd Karma pa. He was also a great traveller who journeyed widely across and beyond Tibet. He met Qubilai Khan in the capital of Yuan China and visited sacred Buddhist sites in South India. He has been aptly described by van der Kuijp as "the great Tibetan yogi, thaumaturge, scholar, alchemist, and traveler". Thanks to the availability of a large amount of hitherto unknown materials from eleven biographies, the thesis has put considerable weight on the bibliographical comparison and analysis of the different works in an attempt to establish the possible relationship between them. This is supplemented by summaries of the biographies, to give an overview of the protagonist's life in Part One of the thesis. Part Two consists of a critical study of the different phases and aspects of U rgyan pa's life in the unique historical, political and religious context of each phase, drawing materials from the corpus of biographies and in the light of other primary and secondary sources in Tibetan, Chinese and Western languages. In Chapter I, U rgyan pa's family lineage, childhood and early studies are discussed in order to find out how his innate propensities and early studies are represented as having influenced his character. In Chapter II, the account of U rgyan pa's journey to West Tibet and U rgyan is studied. A sixteen-stanza song in his own words epitomising this journey, supplemented by route maps, will be used as a framework to illustrate and reconstruct his journey to the Land of the Ḍākinīs. In Chapter III, the teachings he received and the subsequent transformation of his character and status, are explored. In Chapter IV, his career as a tantric master, his other pilgrimages and benediction trips, and his conflicts with various religious and political authorities, are examined. The materials will be scrutinised in the hope of separating as far as possible fact from fiction.