SERS (surface-enhanced Raman spectroscopy) has the potential to be used in a variety of commercial and basic applications, which often rely on molecules that are bound to a nanostructured metal surface. Thiols are usually used as the intermediate to modify the substrate surface for SERS. In recent years, N-heterocyclic carbene (NHC) has been introduced as an alternative approach for metal surface modification. Nanostructured gold surfaces suitable for SERS had been modified by NHC species. Those studies showed the promising of the NHC modification route for the fabrication of a robust platform for SERS. The objective of this work is to explore the SERS characteristics of NHC species on silver surfaces. The interactions between two different NHC molecules and a nanostructured silver surface, instead of a gold surface, were studied for the first time. The experiments were realized in electrochemical conditions, using a three-electrodes system, to fully test the stability of the NHC-modified surfaces. The SERS spectra were compared to theoretical calculations and normal Raman in order to identify the vibrational characteristics of the NHC molecules. The effects of different NHC molecule substituents on the electrochemical stability of the surface were also discussed. The results showed that NHC molecules can be decomposed on the silver surface easily under electrochemical conditions. This contrast with the observations in gold, where the NHC monolayers showed a high level of stability. This work also discusses potential side products which may be derived from the decomposition of the NHC molecules. Raman spectra of potential side products were collected and compared to the NHC SERS collected under electrochemical control at different potentials. This study provides insights into the influence of the substituents at the NHC on their stability under the electrochemical condition, which should guide the development of future applications. / Graduate

El desarrollo de nuevos catalizadores solubles en agua, así como el estudio de su aplicación a distintas transformaciones químicas, sus propiedades fisicoquímicas y su potencial recuperación, es un aporte muy significativo a la catálisis organometálica, y a la química orgánica en general. La presente Tesis, organizada en cinco capítulos, comprende la síntesis, caracterización y aplicaciones de 12 complejos de oro(I) con ligandos carbeno Nheterocíclico (NHC) derivados del imidazol (capítulos 1-4) y un resumen de los resultados obtenidos en una estancia doctoral realizada en el exterior (capítulo 5). En el capítulo 1 se describen las metodologías sintéticas llevadas a cabo para la generación de los ligandos y sus correspondientes complejos, así como el estudio de su estabilidad en medio acuoso. De los complejos sintetizados, seis de ellos contienen grupos sulfonato en su estructura y los restantes son neutros, por lo que mediante el tratamiento con KPF6 o AgSCN, rinden las correspondientes especies iónicas. La caracterización se realizó mediante técnicas complementarias (RMN, FT-IR, UV-Vis, EM) y, en el caso de los complejos, en colaboración con los Dres. Marcelo Ceolín y Agustín Picco (INIFTA-La Plata), se empleó la Espectroscopía de Absorción de Rayos X de Estructura Fina (XAFS). El capítulo 2 trata sobre un exhaustivo estudio catalítico, en medio acuoso, de los complejos sintetizados así como su reciclaje y reutilización. La especie activa fue generada por tres vías diferentes: i) térmica; ii) empleando sales de plata; iii) mediante la asistencia de radiación de microondas o ultrasonido. En colaboración con la Dra. Viviana Dorn (INQUISUR-UNS) se realizaron cálculos teóricos que apoyan los resultados experimentales obtenidos. Por otro lado, teniendo en cuenta la inestabilidad de ciertos complejos, en colaboración con el grupo del Dr. Mariano Correa (UNRC), se estudió la generación de Au-NPs y su estabilización con sales de imidazolio sulfonadas (capítulo 3). En el capítulo 4, teniendo en cuenta la hidrofilia de los complejos sulfonados, se evaluó su eficacia antibacterial frente a bacterias Gram+ y Gram-, en comparación con sus respectivos ligandos. Los estudios biológicos fueron realizados en colaboración con las Dras. M. Soledad Vela Gurovic (CERZOS) y Nelda Olivera (CENPAT). Finalmente, el capítulo 5 describe la síntesis de 5 complejos de oro(I) generados a partir de indazoles y 3 conteniendo fosfinas, junto con los resultados preliminares obtenidos en la cicloisomerización de eninos. Este trabajo fue realizado en colaboración con el Dr. Javier Carreras (ICIQ), bajo la supervisión del Dr. Antonio M. Echavarren (ICIQ). / The development of new water-soluble catalysts and the study of their application to different chemical transformations, physicochemical properties and potential recovery is a very significant contribution to organometallic catalysis, and organic chemistry in general. This thesis, organized in five chapters, includes the synthesis, characterization and applications of 12 gold(I) complexes with imidazole-derived N-heterocyclic carbene (NHC) ligands (Chapters 1-4) and a summary of the results obtained in a doctoral stay abroad (chapter 5). In Chapter 1, synthetic methodologies carried out for the generation of the ligands and their corresponding complexes and the study of its stability in aqueous medium are described. Six complexes contain sulphonate groups in its structure and the rest are neutral, which by treatment with AgSCN or KPF6, generate the corresponding ionic species. The characterization was done by complementary techniques (NMR, FT-IR, UV-Vis, MS) and, in the case of complexes, in collaboration with Dr. Marcelo Ceolín and Agustin Picco (INIFTA-La Plata), Spectroscopy X-ray absorption fine-structure (XAFS) was used. Chapter 2 deals with a comprehensive catalytic study in aqueous medium of the complexes synthesized, and their recycling and reuse. The active species was generated by three different ways: i) heating; ii) silver salts; iii) microwave radiation or ultrasound assistance. Theoretical studies, in collaboration with Dr. Viviana Dorn, support the experimental results. On the other hand, considering the instability of certain complexes, in collaboration with Dr. Mariano Correa (UNRC), the generation of Au-NPs and their stabilization with sulphonated imidazolium salts, was studied (Chapter 3). In Chapter 4, considering the hydrophilicity of sulphonated complexes, its antibacterial effectiveness against Gram + and Gram- bacteria, compared to their respective ligands, was evaluated. Biological studies were conducted in collaboration with Dr. M. Soledad Vela Gurovic (CERZOS) and Nelda Olivera (CENPAT). Finally, Chapter 5 describes the synthesis of 5 complexes of gold(I) generated from indazoles and 3 containing phosphines, as well as preliminary results obtained in cycloisomerization of enynes. This work was performed in collaboration with Dr. Javier Carreras (ICIQ), under the supervision of Dr. Antonio M. Echavarren (ICIQ).

We develop and analyze a combination of techniques to improve timing measurement accuracy of systems processing Gaussian pulses distorted by noise. The approach involves M/N detection, integration, and either correlation or threshold timing measurement techniques. The gain of this process is an increase of the detection capabilities of the system: improvement of the detection probability and decrease in false alarm probability, reduction in pulse distortion, and increase of the accuracy of time delay measurements between pulses using either threshold or correlation measurement methods. Each element of the proposed architecture is studied separately, and modeled analytically. As a result, a design method is proposed in order to develop an appropriate solution to any system requiring accurate time delay measurements in noisy environments. This general method is then applied to a real system, and the results in terms of detection improvement and rms timing error of the method meet expectations: the signal to noise ratio (SNR) operating point of the system is lowered by 10dB, and correlation proves to generate 2dB less rms timing error than threshold. / Master of Science

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Alzheimer's Disease (AD) is an irreversible, age-related neurodegenerative disorder which causes cognitive impairment and a wide variety of neuropsychiatric and behavioral disturbances. Acetylcholinesterase inhibitors (AChEI) are the mainstay for the treatment of AD. Acetylcholinesterase (AChE) catalyzes the hydrolysis of acylcholinesters with a relative specificity for acetylcholine (ACh). Observation of a deficiency of cholinergic neurotransmission in AD led to the development of AChEI as the first approved treatment for dementia symptoms. Tacrine (9-amino-1,2,3,4-tetrahydroacridine) is a reversible inhibitor of AChE. It was the first drug approved by the FDA for the treatment of cognitive symptoms of AD. Tacrine is now rarely prescribed as a drug for the treatment of AD due to its high hepatotoxicity in almost 50% of the patients. However, tacrine derivatives have considerable potential for the palliative treatment of AD. Synthesis of various bivalent tacrines led to the improvement in inhibitory potency and selectivity towards inhibition of AChE. Heptylene-linked bis-tacrine has especially shown immense promise to be an ideal AChEI. Thus dimerization of a lead compound seemed to be an ideal strategy where the compound can bind to both catalytic anionic site (CAS) and peripheral anionic site (PAS) on the AChE enzyme. However synthesis of N-alkyl derivatives of expanded tacrines like 12-chloro-2-methyl-6,7,8,9,10,11-hexahydrocycloocta[b]quinoline by the standard SNAr methods was unsuccessful and thus alternatives needed to be developed to synthesize N-alkylated and bivalent 12-chloro-2-methyl-6,7,8,9,10,11-hexahydrocycloocta[b]quinoline. Upon exploring the alternatives, N-arylation by Pd-catalysis seemed to be the most mild and convenient alternative over the standard SNAr procedures. / Master of Science

Yes / Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator−activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator−activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator−activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris.

Ce mémoire constitue une analyse et une mise en contexte de mon évolution, en tant qu'artiste et en tant qu'homme, voulant expliquer ma démarche artistique ainsi que tout le questionnement découlant de la réalisation d'un corpus d'oeuvres lors de mes deux années à la maîtrise. Cette recherche questionne entre autres la nature de l'image identitaire, son symbolisme et mon processus de création amenant à une modification de cette même image. Ce texte présente donc une analyse personnelle face à l'ouverture occasionnée par l'appropriation et la création d'une image matière.

Mon mémoire est un essai bibliographique. Une tentative pour trouver naturellement une manière d’écrire et de discuter. Une recherche d’une forme authentique pour développer une pensée conséquente de mon travail d’atelier et par le fait même, éviter de décrire ce dernier. J’ai l’ambition d’évoquer implicitement la peinture, pour progresser, ou régresser, vers une sensation de crédibilité des choses. Some Writings est un exercice dont le cadre n’est pas théorique, mais littéraire, pour évoquer des choses indirectement, par analogie.

Ce texte est un accompagnement théorique de l'exposition Piscines, présentée au mois de juin 2008 à la Galerie des Arts Visuels de l'Université Laval. J'y traite de mon travail de création en explicitant les points théoriques et formels essentiels : la représentation et ses mécanismes, le factice et l'apport des traces du travail, le jeu et sa relation à l'art et au rite, et enfin, l'hétérotopie et son rapport à la problématique du fragment et de la totalité.

Ce texte d'accompagnement pose une réflexion sur mon projet de recherche création en arts visuels portant sur le diptyque en peinture et sur sa relation avec ma pratique artistique. Mon projet de maîtrise est constitué de quatorze peintures qui m'ont permis d'établir des confrontations, des formes de duels ou d'échos entre mes œuvres. J'ai observé mes diptyques et j'ai posé une réflexion sur mon processus de création et sur l'origine de chaque oeuvre. De plus, j'ai réfléchi sur le continuum de cette série et étudié l'impact du diptyque dans ma production artistique. Cette recherche vise à accroître mes connaissances sur ma pratique en arts visuels tout en m'aidant à mieux comprendre ma vie de jeune femme artiste dans la vingtaine. / This accompanying text describes an art-based research project that consists of my study of the diptych in painting and its relation to my art. I created fourteen paintings and was able to construct confrontations, forms of duels and echoes, and paintings that compliment each other. I examined my diptychs while reflecting on my creative process and the origin of each painting. Also, I reflect on the continuum of my series, as well as the impact of the diptych on my paintings. The goal of this research was to gain understanding on the continuum of my art practice while shedding light on my life as a young woman artist in her twenties.