Das Ziel dieser Dissertation besteht darin, die Realisierbarkeit der Berechnungen der Niederenergie-Konstanten der chiralen Lagrangedichte zur Gewinnung physikalischer Informationen im epsilon--Regime der quenched QCD zu erforschen. Wir haben der Neuberger Operator und Overlap Hyperkubus Operator eingesetzt. Ein Hauptergebniss dieser Arbeit ist der Vergleich der Wahrscheinlichkeitsverteilungen einzelner Eigenwerte des Neuberger Operators in der QCD mit den analytischen Vorhersagen der Theorie der Zufallsmatritzen. Wir beobachten eine gute Übereinstimmung solange jede Seite des physikalischen Volumens größ er als etwa 1.12 fm ist. Dabei kann auch das chirale Kondensat Sigma abgeschätzt werden. Es ergab sich, daß diese untere Schranke von L allgemein gilt und die Größ e des physikalischen Volumens, auf dem der Axialkorrelator den Vorhersagen des chiralen Störungstheorie folgt, festlegt. Damit koennen wir die Pionzerfallskonstante bestimmen. Unsere Simulationen zeigen, daß wegen der groß en Wahrscheinlichkeit niedriger Eigenwerte die Messung des Axialkorrelators im topologischen neutralen Sektor extrem aufwändig ist. Doch reicht die Empfindlichkeit der Vorhersagen der chiralen Störungstheorie in höheren topologischen Sektoren bei der gegebenen Statistik nicht zur Bestimmung von Sigma aus. Als alternative Methode, gehen wir dazu über, allein den Beitrag der Nullmoden zu betrachten. Hier koennen wir Abschätzungen für die Pionzerfallskonstante und alpha gewinnen. Wir berechnen die topologische Suszeptibilität für den Neuberger und Overlap Hyperkubus Operator. Im letzten Fall ist der berechnete Wert näher beim Kontinuumslimes. Die Lokalisierung für den Overlap Hyperkubus Operator ist auch besser als für den Neuberger Operator. Unser anderes Ziel ist die Erforschung einer topologieerhaltenden Eichwirkung. / This thesis is dedicated to explore the feasibility of extraction of the low energy constants of the chiral Lagrangian in the epsilon--regime of quenched QCD. We apply two formulations of the Ginsparg-Wilson fermions, namely, the Neuberger operator and the hypercube overlap operator to compute the observables of interest. As a main result we present the comparison of the distributions of the leading individual eigenvalues of the Neuberger operator in QCD and the analytical predictions of chiral random matrix theory. We observe a good agreement as long as each side of the physical volume exceeds about 1.12 fm. At the same time the chiral condensate Sigma can also be estimated. It turns out that this bound for L is generic and sets the size of the physical volume where the axial correlator behaves according to chiral perturbation theory. This allows us to compute a value for the pion decay constant. The simulations also show that due to the high probability of the near-zero modes it is prohibitively difficult to sample the axial correlator in the neutral topological sector. In the higher sectors, however, we observe that the sensitivity of the analytical predictions for the axial correlator to extract Sigma is lost to a large extent. As an alternative procedure we only consider the contribution from the zero modes. Here we are able to obtain an estimate for the pion decay constant and alpha, where alpha is a low energy constant peculiar to quenching. We calculate the topological susceptibility, both for the Neuberger operator and for the overlap hypercube operator. It turns out that the result with the overlap hypercube operator is closer to the continuum limit. Also the locality properties are superior to those of the Neuberger fermions. As a theoretical development the Lüscher topology conserving gauge action is investigated. This enables us to sample the observables of interest in the epsilon--regime without recomputing the index.

Os não-carbeno complexos pentacoordenados do tipo [RuCl2(PPh3)2(amina)], sendo as aminas pirrolidina, azocano e dietilamina, foram sintetizados e caracterizados por análise elementar, espectroscopia de absorção na região do infravermelho, espectroscopia de absorção na região do ultravioleta e visível, espectroscopia de ressonância magnética nuclear de fósforo-31 e espectroscopia de ressonância paramagnética eletrônica. Estudos da teoria do funcional da densidade dos complexos foram realizados para buscar melhor interpretação dos resultados experimentais obtidos. O complexo [RuCl2(PPh3)2(pirrolidina)] exibiu uma geometria do tipo pirâmide de base quadrada em solução, com a amina na posição apical e as trifenilfosfinasestão trans-posicionada. Os complexos [RuCl2(PPh3)2(azocano)] e [RuCl2(PPh3)2(dietilamina)] exibiram geometria do tipo bipirâmide trigonal na qual as duas trifenilfosfinas estão trans-posicionadas no eixo axial. O complexo [RuCl2(PPh3)2(pirrolidina)] exibiu boa atividade catalítica nas polimerizações de norborneno e norbornadieno, tanto em atmosfera de argônio quanto em ar a 25 °C, como observado com os complexos similares [RuCl2(PPh3)2(peridroazepina)] e [RuCl2(PPh3)2(piperidina)]. Os complexos [RuCl2(PPh3)2(azocano)] e [RuCl2(PPh3)2(dietilamina)] obtiveram baixo rendimento de polimerização mesmo a 40 °C. Acredita-se que a geometria do tipo pirâmide de base quadrada seja a ativa para formação da espécie metal-carbeno com o etil diazoacetato no período de indução e favorável para iniciar a reação de polimerização via metátese por abertura de anel. A geometria do tipo bipirâmide trigonal pode dificultar o período de indução. Os estudos teóricos corroboraram com essa discussão. Os polinorbornenos, polinorbornadienos e seus copolímeros obtidos com os três complexos ativos foram caracterizados por espectroscopia de ressonância magnética nuclear de carbono-13, calorimetria exploratória diferencial, análise dinâmico-mecânica, termogravimetria e microscopia eletrônica de varredura. O complexo [RuCl2(PPh3)2(peridroazepina)] foi eficiente na metátese cruzada entre lignina metacrilada e o 10-undecen-1-ol para modificar a lignina Protobind 2400, e a lignina modificada foi solúvel em diversos solventes. O complexo [RuCl2(PPh3)2(peridroazepina)] também foi utilizado na autometátese da olefina terminal do 10-undecen-1-ol para obtenção de um diol que foi usado como segmento flexível e extensor de cadeia em reações de poliuretanas com óleo de mamona ou poli(ε-caprolactona) diol. Esse diol, quando utilizado em pequenas quantidades (10% em massa) nas poliuretanas derivadas do óleo de mamona, foi capaz de prover características adesivas a um material inicialmente rígido. Os resultados das reações de poliuretanas derivadas da poli(ε-caprolactona) diol não apresentaram resultados satisfatórios. / Non-carbene five-coordinate [RuCl2(PPh3)2(amina)] complexes, with pyrrolidine, azocane and diethylamine, were synthesized and characterized by elemental analysis, infrared absorption spectroscopy, ultraviolet-visible absorption spectroscopy, phosphorus-31 nuclear magnetic resonance and electron paramagnetic resonance. Density functional theory studies of the complexes were performed to complete and improve the experimental studies. [RuCl2(PPh3)2(pyrrolidine)] presented a square pyramidal geometry in solution, with the amine in the apical position and trans-positioned phosphines. [RuCl2(PPh3)2(azocane)] and [RuCl2(PPh3)2(diethyl amine)] exhibited a trigonal bipyramidal geometry in solution, with two phosphine molecules trans-positioned in the axial axis. [RuCl2(PPh3)2(pyrrolidine)] presented activity for ring opening metathesis polymerization of norbornene and norbornadiene under either air or inert atmosphere of argon at 25 °C, as observed with the parent complexes with perhydroazepine and piperidine. The latter three complexes presented square pyramidal geometries and high yields of polynorbornene and polynorbornadiene, different from the trigonal bipyramidal geometry of the complexes with azocane and diethylamine, which showed lower yields for polymerization even at 40 °C. This suggests that the cyclic amines in the apical position of the square pyramidal geometry provoke less steric hindrance, which provides prompt reactivity for ring opening metathesis polymerization. The bipyramidal geometry can hinder the induction period. Theoretical studies corroborate this discussion. The polynorbornenes, polynorbornadienes, and their copolymers obtained with the three active complexes were characterized by carbon-13 nuclear magnetic resonance, differential scanning calorimetry, dynamic mechanical analysis, thermogravimetry analysis, and scanning electron microscopy. [RuCl2(PPh3)2(perhydroazepine)] was efficient to perform cross metathesis between the methacrylate lignin and 10-undecen-1-ol to modify the Protobind 2400 lignin, and the modified lignin was soluble in several solvents. Self-metathesis of the terminal olefin in 10-undecen-1-ol was conducted in the presence of [RuCl2(PPh3)2(perhydroazepine)] and ethyl diazoacetate to form a bioderived diol. The diol was utilized as soft segment and chain extender in polyurethane reactions with castor oil or poly(ε-caprolactone) diol. At only 10 wt% of the diol, an adhesive characteristic was observed in the castor oil-based polyurethane. The results from poly(ε-caprolactone) diol-based polyurethane were not satisfactory.

L'objectif de cette thèse est d’encapsuler l'indométacine dans des nanoparticules polymériques en association à l’huile essentielle de Nigella Sativa L. extraite à partir de ses graines afin d’optimiser son utilisation par voie cutanée et potentialiser son activité anti-inflammatoire.Pour ce faire, des nanoparticules à base de poly-epsilon-caprolactone ont été préparées par nanoprécipitation. Une étude systématique a été menée pour comprendre l'effet de la variation des paramètres de préparation sur les propriétés colloïdales des nanoparticules obtenues. Une fois les différents paramètres optimisés, l'indométacine et l'huile essentielle de Nigella Sativa L. ont été encapsulées séparément dans les nanoparticules polymériques. Puis, l’ensemble, indométacine et huile essentielle de Nigella Sativa L. a été encapsulé. Les nanoparticules préparées ont à chaque fois été caractérisées notamment en termes de stabilité et de performance d’encapsulation. Ensuite, nous avons mené une étude ex vivo et in vivo des nanoparticules obtenues afin d’évaluer le potentiel de pénétration cutanée d’une part, et le potentiel clinique dans la prise en charge de l’inflammation / The objective of this PhD thesis was to extract the Nigella Sativa L. Seeds Essential Oil and its encapsulation together with indomethacin within polymeric nanoparticles in order to reduce taken amount and to enhance indomethacin cutaneous penetration, and anti-inflammatory activity. To this direction poly-epsilon-caprolactone based nanoparticles were designed using nanoprecipitation method. A systematic study was performed to figure out the effect of process and formulation parameters on the characteristics of obtained nanoparticles. Once the effects of all parameters were studied, then indomethacin and Nigella Sativa L. Seeds Essential Oil was encapsulated separately. Consequently, both together indomethacin and Nigella Sativa L. Seeds Essential Oil was encapsulated. Then prepared nanoparticles were characterized in terms of stability, encapsulation efficiency. In addition, ex vivo skin penetration and in vivo anti-inflammatory activity of designed nanoparticles was investigated

The mutated forms of the Discs overgrown gene causes overproliferation of imaginal discs of Drosophila melanogaster. Somatic mutations in its human counterpart, casein kinase I epsilon, were strongly associated with human breast cancer. Using the advantage of a high conservancy between fly's dco and human casein kinase I epsilon genes we have chosen D. melanogaster as a model organism to provide a list of probable Dco interaction partners via tandem affinity purification and mass spectrometry analysis. However, these proteins need to be independently verified as true Dco interaction partners.

In this thesis we consider extensions and generalizations of some classical problems in Combinatorial Geometry. Our work is an offshoot of four classical problems in Combinatorial Geometry. A fundamental assumption in these problems is that the underlying point set is R2. Two fundamental themes entwining the problems considered in this thesis are: “What happens if we assume that the underlying point set is finite?”, “What happens if we assume that the underlying point set has a special structure?”. Let P ⊂ R2 be a finite set of points in general position. It is reasonable to expect that if |P| is large then certain ‘patterns’ in P always occur. One of the first results was the Erd˝os-Szekeres Theorem which showed that there exists a f(n) such that if |P| ≥ f(n) then there exists a convex subset S ⊆ P, |S| = n i.e., a subset which is a convex polygon of size n. A considerable number of such results have been found since. Avis et al. in 2001 posed the following question which we call the n-interior point problem: Is there a finite integer g(n) for every n, such that, every point set P with g(n) interior points has a convex subset S ⊆ P with n interior points. i.e. a subset which is a convex polygon that contains exactly n interior points. They showed that g(1) = 1, g(2) = 4. While it is known that g(3) = 9, it is not known whether g(n) exists for n ≥ 4. In the first part of this thesis, we give a positive solution to the n-interior point problem for point sets with bounded number of convex layers. We say a family of geometric objects C in Rd has the (l, k)-property if every subfamily C′ ⊆ C of cardinality at most l is k-piercable. Danzer and Gr¨unbaum posed the following fundamental question which can be considered as a generalised version of Helly’s theorem: For every positive integer k, does there exist a finite g(k, d) such that if any family of convex objects C in Rd has the (g(k, d), k)-property, then C is k-piercable? Very few results(mostly negative) are known. Inspired by the original question of Danzer and Gr¨unbaum we consider their question in an abstract set theoretic setting. Let U be a set (possibly infinite). Let C be a family of subsets of U with the property that if C1, . . . ,Cp+1 ∈ C are p + 1 distinct subsets, then |C1 ∩ · · · ∩Cp+1| ≤ l. In the second part of this thesis, we show in this setting, the first general positive results for the Danzer Grunbaum problem. As an extension, we show polynomial sized kernels for hitting set and covering problems in our setting. In the third part of this thesis, we broadly look at hitting and covering questions with respect to points and families of geometric objects in Rd. Let P be a subset of points(possibly infinite) in Rd and C be a collection of subsets of P induced by objects of a given family. For the system (P, C), let νh be the packing number and νc the dual packing number. We consider the problem of bounding the transversal number τ h and the dual transversal number τ c in terms of νh and νc respectively. These problems has been well studied in the case when P = R2. We systematically look at the case when P is finite, showing bounds for intervals, halfspaces, orthants, unit squares, skylines, rectangles, halfspaces in R3 and pseudo disks. We show bounds for rectangles when P = R2. Given a point set P ⊆ Rd, a family of objects C and a real number 0 < ǫ < 1, the strong epsilon net problem is to find a minimum sized subset Q ⊆ P such that any object C ∈ C with the property that |P ∩C| ≥ ǫn is hit by Q. It is customary to express the bound on the size of the set Q in terms of ǫ. Let G be a uniform √n × √n grid. It is an intriguing question as to whether we get significantly better bounds for ǫ-nets if we restrict the underlying point set to be the grid G. In the last part of this thesis we consider the strong epsilon net problem for families of geometric objects like lines and generalized parallelograms, when the underlying point set is the grid G. We also introduce the problem of finding ǫ-nets for arithmetic progressions and give some preliminary bounds.

Chez les plantes, les méristèmes ont la capacité de se diviser tout au long de la vie de la plante, qui peut dépasser 1000 ans pour certaines espèces. De plus, la lignée germinale n'est pas définie dès l'embryogenèse mais provient des cellules méristématiques et s’individualise relativement tard au cours du développement. Il est donc crucial que le cycle cellulaire soit finement régulé afin d'éviter une accumulation de mutations au cours de la croissance végétative et de la reproduction. Chez tous les eucaryotes, les protéines CDT1 sont impliquées dans l’initiation de la réplication de l'ADN en permettant la formation du complexe de pré-réplication et l'ouverture de la fourche de réplication avant le recrutement des ADN polymérases. Leur activité est strictement régulée afin que chaque partie du génome soit répliquée une fois et une seule au cours de la phase S. Le génome d’Arabidopsis thaliana code pour deux protéines homologues du facteur d’initiation de la réplication CDT1 (CDC10 Target1) : AtCDT1a et AtCDT1b. La sur-expression de CDT1a stimule la réplication de l’ADN et, chez Arabidopsis, cette protéine aurait une double fonction dans la régulation du cycle cellulaire et dans la division des plastes. Nous avons étudié ici les fonctions respectives de AtCDT1a et AtCDT1b. En utilisant des approches génétiques, nous avons montré que ces deux protéines jouent des rôles partiellement redondants pour maintenir l’intégrité du génome et permettre le développement des gamétophytes. De plus, en réalisant une approche de TAP (Tandem Affinity Purification), nous avons montré qu’elles interagissent avec l’ADN polymérase ε, une ADN polymérase réplicative, ouvrant de nouvelles perspectives de recherche concernant le rôle des protéines CDT1de plantes lors de la réplication de l'ADN. En parallèle, nous avons essayé d'élucider les spécificités de CDT1a et plus précisément de son extension N-terminale qui est absente de CDT1b. Nous avons constaté que ce domaine de CDT1a est requis pour son interaction avec l'ADN pol ε, et que les mutants cdt1a complémentés par une version tronquée de la protéine présentent une croissance considérablement réduite, un arrêt prématuré du méristème racinaire, et un stress de l'ADN constitutif, ce qui suggère que l’interaction CDT1a/pol ε est indispensable à la progression normale de la phase S. L’ensemble de nos résultats ont révélé de nouvelles fonctions pour les homologues de CDT1 de plantes. Une question importante sera de déterminer si celles-ci sont caractéristiques du cycle cellulaire chez les plantes, ou si nous avons identifié de nouveaux mécanismes qui sont conservés chez tous les eucaryotes. / In plants, meristems retain the ability to divide throughout the life cycle of plants, which can last for over 1000 years in some species. Furthermore, the germline is not laid down early during embryogenesis but originates from the meristematic cells relatively late during development. Thus, accurate cell cycle regulation is of utmost importance to avoid the accumulation of mutations during vegetative growth and reproduction. In all eukaryotes, CDT1 proteins are involved in the onset of DNA replication by allowing the formation of the pre-replication complex and subsequent opening of the replication fork. Their activity is strictly regulated to ensure faithful duplication of the genome during S-phase. The Arabidopsis thaliana genome encodes two homologs of the replication licensing factor CDT1 (CDC10 Target 1): AtCDT1a and AtCDT1b. Overexpression of CDT1a stimulates DNA replication, and this protein would have a function both in cell cycle regulation and plastid division.Here, we have investigated the respective roles of Arabidopsis CDT1a and CDT1b. Using genetic approaches, we have shown that the two proteins function partially redundantly to maintain genome integrity and allow gametophyte development. In addition, using Tandem Affinity Purification, we have shown that they interact with DNA pol ε, a replicative DNA polymerase, opening further research prospects regarding the role of plant CDT1 proteins during DNA replication. In parallel, we have tried to elucidate the specificities of CDT1a and more precisely of its N-terminal extension that is absent from CDT1b. We have found that this domain of CDT1a is required for its interaction with DNA pol ε, and that cdt1a mutants complemented with a truncated version of the protein show drastically reduced growth, premature meristem arrest, and constitutive DNA stress, suggesting that the CDT1a/pol ε interaction is indispensible to the normal progression of S-phase. Together, our results have unraveled new functions for plant CDT1 homologues, and one important aspect of future research will be to determine whether these are features of the plant cell cycle, or if we have identified new mechanisms that are conserved in all eukaryotes.

This dissertation focuses on aerosol transport modeling in occupational environments and mining sites in Arizona using computational fluid dynamics (CFD). The impacts of human exposure in both environments are explored with the emphasis on turbulence, wind speed, wind direction and particle sizes. Final emissions simulations involved the digitalization process of available elevation contour plots of one of the mining sites to account for realistic topographical features. The digital elevation map (DEM) of one of the sites was imported to COMSOL MULTIPHYSICS® for subsequent turbulence and particle simulations. Simulation results that include realistic topography show considerable deviations of wind direction. Inter-element correlation results using metal and metalloid size resolved concentration data using a Micro-Orifice Uniform Deposit Impactor (MOUDI) under given wind speeds and directions provided guidance on groups of metals that coexist throughout mining activities. Groups between Fe-Mg, Cr-Fe, Al-Sc, Sc-Fe, and Mg-Al are strongly correlated for unrestricted wind directions and speeds, suggesting that the source may be of soil origin (e.g. ore and tailings); also, groups of elements where Cu is present, in the coarse fraction range, may come from mechanical action mining activities and saltation phenomenon. Besides, MOUDI data under low wind speeds (<2 m/s) and at night showed a strong correlation for particles 1-micrometer in diameter between the groups: Sc-Be-Mg, Cr-Al, Cu-Mn, Cd-Pb-Be, Cd-Cr, Cu-Pb, Pb-Cd, As-Cd-Pb. The As-Cd-Pb group correlates strongly in almost all ranges of particle sizes. When restricted low wind speeds were imposed more groups of elements are evident and this may be justified with the fact that at lower speeds particles are more likely to settle. When linking these results with CFD simulations and Pb-isotope results it is concluded that the source of elements found in association with Pb in the fine fraction come from the ore that is subsequently processed in the smelter site, whereas the source of elements associated to Pb in the coarse fraction is of different origin. CFD simulation results will not only provide realistic and quantifiable information in terms of potential deleterious effects, but also that the application of CFD represents an important contribution to actual dispersion modeling studies; therefore, Computational Fluid Dynamics can be used as a source apportionment tool to identify areas that have an effect over specific sampling points and susceptible regions under certain meteorological conditions, and these conclusions can be supported with inter-element correlation matrices and lead isotope analysis, especially since there is limited access to the mining sites. Additional results concluded that grid adaption is a powerful tool that allows to refine specific regions that require lots of detail and therefore better resolve flow detail, provides higher number of locations with monotonic convergence than the manual grids, and requires the least computational effort. CFD simulations were approached using the k-epsilon model, with the aid of computer aided engineering software: ANSYS® and COMSOL MULTIPHYSICS®. The success of aerosol transport simulations depends on a good simulation of the turbulent flow. A lot of attention was placed on investigating and choosing the best models in terms of convergence, independence and computational effort. This dissertation also includes preliminary studies of transient discrete phase, eulerian and species transport modeling, importance of saltation of particles, information on CFD methods, and strategies for future directions that should be taken.

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

The innate immune system provides the body’s first line of defense against pathogenic challenge through pathogen recognition and initiation of the immune response. Among the various cellular mechanisms of pathogen recognition in mammals, Toll-like receptor 3 (TLR3) recognizes viral dsRNA. Stimulation of TLR3 signaling pathway leads to transcription of pro-inflammatory cytokines and type-1 Interferons. Suppressor of IKKε (SIKE) interacts with two kinases in the signaling pathway, IKKε and TANK binding kinase 1 (TBK1), inhibiting the transcription of type I interferons. Recently, the Bell Laboratory discovered that SIKE blocks TBK1-mediated activation of type I interferons by acting as a high affinity, alternative substrate of TBK1. To further characterize SIKE’s function within the antiviral response, this study focused on defining the overall SIKE structure. Using recombinant protein expressed from E. coli and purified via immobilized metal affinity chromatography, SIKE crystals were obtained from a sample concentrated to 15 mg/ml under several crystallization conditions. Yet, reproducing these results has been difficult. In this study, we have modified the purification scheme to remove an E. coli contaminant, SlyD. Purification under denaturing conditions, removal of soluble proteins, incorporation of ion exchange and different IMAC (immobilized metal ion affinity chromatography) resins has been tested. For each scheme, size exclusion chromatography and SDS-PAGE/Coomassie/silver stain were used to assess purity. Crystallization trials for samples from each purification scheme were completed. In addition to crystallization trials, hydrogen-deuterium exchange (HDX) was investigated, accompanied with pepsin digests, in order to further characterize the dynamic structure of SIKE.

The research related to designing portable monitoring devices for physiological signals has been at its peak in the last decade or two. One of the main obstacles in building such devices is the effect of the subject's movements on the quality of the signal. There have been numerous studies addressing the problem of removing motion artifact from the electrocardiogram (ECG) and photoplethysmography (PPG) signals in the past few years. However, no such study exists for the Impedance Plethysmography (IP) signal. The IP signal can be used to monitor respiration in mobile devices. However, it is very susceptible to motion artifact. The main aim of this dissertation is to develop adaptive and non-adaptive filtering algorithms to address the problem of motion artifact reduction from the IP signal.