A scientific and cultural revolution occurred with the sequencing of the human genome. The information provided by this accomplishment has provided tools for researchers to test new ideas in silico and on the bench. In redox biology many of the genes, transcripts, proteins, and redox active species have been well characterized. However, the vast majority have not been quantitated in an absolute manner. This is a necessary step to provide the tools for mathematical modeling and systems biology approaches for predicting changes in the cellular redox environment and the biochemical and biological consequences. Here we demonstrate techniques for the absolute quantitation of human catalase, glutathione peroxidase, peroxiredoxin, thioredoxin, and superoxide dismutase within cells. These techniques can be parsed into two groups: detection of activity and detection of total amount of species. Methods for the absolute quantitation of active catalase, peroxiredoxins, and superoxide dismutase have been developed by utilizing specific characteristics of each enzyme. Catalase generates oxygen in the presence of hydrogen peroxide that can easily be detected with a Clark electrode (oxygen monitor); the data are fit to a single-exponential to determine the observed pseudo-first-order rate constant. From this the effective number of fully active catalase enzymes in the sample can be determined. Peroxiredoxin in the disulfide state can be reduced by thioredoxin; thioredoxin from E. coli loses fluorescence upon oxidation. The loss of fluorescence over time is mathematically fit to a single-exponential to determine the observed pseudo first-order rate constant from which the number of active enzymes can be determined. Using an inhibition assay to detect superoxide dismutase activity along with the rate constants at which superoxide reacts with the dismutase and the competing superoxide-reacting-indicator-molecule, the concentration of active superoxide dismutase can be determined. To detect the total amount of protein of an enzyme in a biological sample, an immunoassay was first implemented. This method utilized Bio-Plex® beads from Bio-Rad; however, it was problematic because the antibodies applied did not perform satisfactorily not allowing sufficient signal-to-noise to be deployed. Quantitative mass spectrometry was then implemented to detect total catalase, glutathione peroxidase 1, peroxiredoxin 2, and thioredoxin 1 in human red blood cells. With the absolute concentration of these enzymes and proteins along with data for oxygen consumption rates and peroxisomal hydrogen peroxide concentration for several cell lines, we hypothesize that a reasonable model of hydrogen peroxide and superoxide flux can be constructed. Quantitative data such as these provide the foundation for the new redox biology of the 21st century. Presented here is a roadmap for the obligatory first steps to dissect quantitatively the cellular and tissue metabolic pathways and redox networks that are the basis of all of biology.

Combustion has been used for a long time as a means of energy extraction. However, in the recent years there has been further increase in air pollution, through pollutants such as nitrogen oxides, acid rain etc. To solve this problem, there is a need to reduce carbon and nitrogen oxides through lean burning, fuel dilution and usage of bi-product fuel gases. A numerical analysis has been carried out to investigate the effectiveness of several reduced mechanisms, in terms of computational time and accuracy. The cases were tested for the combustion of hydrocarbons diluted with hydrogen, syngas, and bi-product fuel in a cylindrical combustor. The simulations were carried out using the ANSYS Fluent 19.1. By solving the conservations equations, several global reduced mechanisms (2-5-10 steps) were obtained. The reduced mechanisms were used in the simulations for a 2D cylindrical tube with dimensions of 40 cm in length and 2.0 cm diameter. The mesh of the model included a proper fine quad mesh, within the first 7 cm of the tube and around the walls. By developing a proper boundary layer, several simulations were performed on hydrocarbon/air and syngas blends to visualize the flame characteristics. To validate the results “PREMIX and CHEMKIN” codes were used to calculate 1D premixed flame based on the temperature, composition of burned and unburned gas mixtures. Numerical calculations were carried for several hydrocarbons by changing the equivalence ratios (lean to rich) and adding small amounts of hydrogen into the fuel blends. The changes in temperature, radical formation, burning velocities and the reduction in NOx and CO2 emissions were observed. The results compared to experimental data to study the changes. Once the results were within acceptable range, different fuels compositions were used for the premixed combustion through adding H2/CO/CO2 by volume and changing the equivalence ratios and preheat temperatures, in the fuel blends. The results on flame temperature, shape, burning velocity and concentrations of radicals and emissions were observed. The flame speed was calculated by finding the surface area of the flame, through the mass fractions of fuel components and products conversions that were simulated through the tube. The area method was applied to determine the flame speed. It was determined that the reduced mechanisms provided results within an acceptable range. The variation of the inlet velocity had neglectable effects on the burning velocity. The highest temperatures were obtained in lean conditions (0.5-0.9) equivalence ratio and highest flame speed was obtained for Blast Furnace Gas (BFG) at elevated preheat temperature and methane-hydrogen fuels blends in the combustor. The results included; reduction in CO2 and NOx emissions, expansion of the flammable limit, under the condition of having the same laminar flow. The usage of diluted natural gases, syngas and bi-product gases provides a step in solving environmental problems and providing efficient energy.

En Allemagne, en Belgique, en France, en Irlande, en Islande, en Slovénie ou au Portugal, la gauche radicale connaît des poussées électorales, atteignant bien souvent des niveaux là aussi inédits. Dans les pays dans lesquels elle est traditionnellement bien implantée, si elle ne perce pas, elle demeure un acteur important de la vie politique et parlementaire, notamment à Chypre, en République tchèque, en Finlande, en Suède. Il est donc pertinent d’interroger le phénomène : pourquoi ce retour en force des partis de la gauche radicale ? Quelles en sont les causes ? Qui sont les acteurs partisans de ce renouveau ? Apporter des réponses à ces questions ne peut que passer par une analyse comparative.La thèse se fixe comme objectif de répondre à deux questions ayant structuré sa rédaction :1/ pourquoi la gauche radicale européenne se transforme-t-elle, quels sont les facteurs provoquant cette transformation en incitant ses dirigeants à l’opérer, et quelle est la nature de ces transformations ?2/ quels sont les objectifs et les attendus de ces transformations, et comment se traduisent-elles par le ralliement de nouveaux électeurs dans le cadre des échéances électorales ?Nous partons en effet du principe qu’un parti ne se transforme pas en vain. S’il amende son identité, son projet, ses discours ou le mode de fonctionnement de son organisation, c’est qu’il escompte franchir un cap dans son développement. Au travers d'une analyse comparative entre l'Allemagne, l'Espagne, la Grèce et le Portugal, nous verrons qu'émerge et se structure une nouvelle gauche radicale impactant durablement la famille partisane de la gauche radicale européenne. / In Germany, Belgium, France, Ireland, Iceland, Slovenia and Portugal, radical left parties are experiencing electoral surges, often reaching new levels as well. In countries where they are traditionally well established, if they don't break through, they remain an important player in political and parliamentary life, particularly in Cyprus, Czech Republic, Finland and Sweden. It is therefore relevant to question the phenomenon: why this return in force of the radical left parties? What are the causes? Who are the actors in favor of this renewal? Answering these questions can only be done through a comparative analysis.The thesis aims to answer two questions that have structured its writing:1 / why is the european radical left transforming itself, what are the factors causing this transformation by encouraging its leaders to operate it, and what is the nature of these transformations?2 / What are the objectives and expectations of these transformations, and how do they translate into the rallying of new voters in the elections?We start from the premise that a party does not change in vain. If a prty amends its identity, its project, its speeches or the mode of operation of its organization, it is that this party expect to cross a course in its development. Through a comparative analysis between Germany, Spain, Greece and Portugal, we will see the emergence and structuring of a new radical left permanently impacting the partisan family of the European radical left.

The process of shock-induced ignition has been investigated both computa- tionally and experimentally, with particular emphasis on the concept of radical farming. The first component of the investigation contained Computational Fluid Dynamic (CFD) calculations of an ignition delay study, a 2D pre-mixed flow over flat plate at a constant angle to the freestream, and through a generic 2D scramjet model. The focal point of the investigation however examined the complex 3D flow through a generic scramjet model. Five experimental test conditions were ex- amined over flow enthalpies from 3.4 MJ/kg to 6.4 MJ/kg. All test conditions simulated flight at 21000 metres ([symbol=almost equal to] 70000 ft), while the equivalent flight Mach number varied from approximately 8.5 at the lowest enthalpy, to approximately Mach 12 at the highest enthalpy condition. The presence of H2 fuel injected in the intake caused a separated region to form on the lower surface of the model at the entrance to the combustor. A fraction of the total mass of fuel was entrained in this separated region, providing long residence times, hence increased time for the chemical reactions that lead to ignition to occur. In addition, extremely high temperatures were found to exist between each fuel jet. Both fuel and air are present in these regions, therefore the chance of ignition in these regions is high. Streamlines passing through the recirculation zone ignited within this zone, while streamlines passing between the fuel jets ignited soon after entry into the combustor. The first instance of a pressure rise from combustion was observed on the centreline of the model where the reflected bow shock around the fuel jets crossed the centreline of the combus- tor. Upstream of this location the static pressure of the flow was too low for the chemical reactions that release heat to occur. The comparison between the experimental and computational results was lim- ited due to inaccuracies in modelling the thermal state of the gas in the CFD calculations. The gas was modelled as being in a state of thermal equilibrium at all times, which incorrectly models the freestream flow from the nozzle of the shock tunnel, and also the flow downstream of oblique shock wave within the scramjet model. As a result combustion occurs sooner in the CFD calculations than in the experimental result.

Nitric oxide is a small free radical generated by family of enzymes, the nitric oxide synthases. In a series of experiments performed over the last 15 years we showed that nitric oxide is induced by all three isoforms of nitric oxide synthase during tendon healing and that it plays a crucial beneficial role in restoring tendon function. In normal tendon we found very little nitric oxide synthase activity while in injured rat and human tendons nitric oxide synthase activity was expressed in healing fibroblasts in a temporal fashion. In healing rat Achilles tendon fibroblasts the first isoform to be expressed was endothelial nitric oxide synthase (eNOS), followed by inducible nitric oxide synthase (iNOS), and then brain or neuronal nitric oxide synthase (bNOS). Systemic inhibition of nitric oxide synthase activity decreased the cross sectional area and mechanical properties of the healing rodent Achilles tendons. Addition of nitric oxide via NO-flurbiprofen or NO-paracetamol enhanced rat Achilles tendon healing. Addition of nitric oxide to cultured human tendon cells via chemical means and via adenoviral transfection enhanced collagen synthesis, suggesting that one mechanism for the beneficial of nitric oxide on tendon healing might be via matrix synthesis. The final part of the work involved three randomized, double-blind clinical trials which evaluated the efficacy of nitric oxide donation via a patch in the management of the tendinopathy. In all three clinical trials there was a significant positive beneficial effect of nitric oxide donation to the clinical symptoms and function of patients with Achilles tendinopathy, tennis elbow and Achilles tendonitis.

The research reported in this thesis was carried out in Brisbane, Australia and Calgary, Canada. The aim of the research conducted in Brisbane was to prepare a series of copper(I) and ruthenium(II) based complexes incorporating a hemilabile phosphine ligand and to determine whether or not these compounds possessed catalytic activity. The history, uses, properties and recent work incorporating hemilabile phosphine ligands is discussed in detail as well as the application of hemilabile ligands to atom transfer radical polymerization (ATRP) and the usefulness of the 'windscreen wiper' action of these ligands in polymerization. The literature synthesis and characterization of four hemilabile phosphine ligands is reported with modifications. The (2-chlorophenyl)diphenylphosphine ligand was prepared via a Grignard reaction giving a 11% yield. The (2-bromophenyl) diphenylphosphine ligand was prepared by reaction of 2-bromoiodobenzene with Ph2PSiMe3 in the presence of a palladium catalyst (MeCN)2PdCl2 which yielded 50% product. The 1-chloro-2-diphenylphosphinoethane ligand was prepared following the generation of a lithium diphenylphosphide which was added to 1,2-dichloroethane to give a 43% yield of product. The (2-benzoic-acid)diphenylphosphine ligand was prepared by hydrolysis of (2-methyl-ester-phenyl)diphenylphosphine. Following acidification of the methyl ester phosphine with HCl, the desired product was isolated in 88% yield. The synthesis and characterization of a series of copper(I) based complexes incorporating the prepared phosphine ligands involved reaction in CH3CN of the appropriate ligand with copper halides as starting material. Solution state 31P NMR and mass spectrometry were used to study many of these complexes in the solution state, whilst microanalysis, 31P CP MAS NMR and single crystal X-ray diffraction studies were used to study their solid state properties. The complexes of the type bis(2-halophenyl)diphenylphosphine copper halide were found to be three coordinate with non-chelating ligands and to be isostructural with the previously studied bis(2-methylphenyl)diphenylphosphine copper halide complexes. The synthesis and characterization of ruthenium(II) based complexes incorporating hemilabile phosphine ligands involved reaction of the appropriate ligands in MeOH with RuCl3.3H2O or RuCl2(DMSO)4 as the ruthenium source. Modes of characterization included solution state 31P NMR, mass spectrometry, microanalysis and single crystal X-ray diffraction studies. All ruthenium(II) based complexes were found to incorporate the hemilabile ligands in a chelating mode resulting in 6 coordinate structures. The preliminary polymerization testing of MMA in the presence of the copper(I) and ruthenium(II) based complexes has been reported. All complexes successfully polymerized the monomer and the resulting polyMMA showed polydispersity values ranging from moderate (3.1) to very high (6.7). Chapter 7 discusses research conducted over a 6 month period at the University of Calgary, Canada under an International Resident Fellowship award. This work involved the synthesis and characterization of scandium(III) and yttrium(III) based complexes incorporating a chelating amido-imine ligand, as potential olefin polymerization catalysts.

LA GALACTOSE OXYDASE EST UNE METALLOENZYME DU CUIVRE QUI CATALYSE L'OXYDATION AEROBIQUE DES ALCOOLS PRIMAIRES EN ALDEHYDE AVEC REDUCTION CONCOMITANTE D'UNE MOLECULE DE DIOXYGENE EN PEROXYDE D'HYDROGENE. SON SITE ACTIF RENFERME L'ASSOCIATION ORIGINALE CUIVRE(II)-RADICAL TYROSINYLE QUI EMMAGASINE DEUX EQUIVALENTS OXYDANTS.<br />A PARTIR DE COMPLEXES DU CUIVRE MODELES, NOUS AVONS REPRODUIT CETTE ASSOCIATION ET L'AVONS ETENDUE A DES STRUCTURES PLUS COMPLEXES POUVANT EMMAGASINER TROIS ET QUATRE EQUIVALENTS OXYDANTS.<br />EN PREMIER LIEU, NOUS AVONS PREPARE DES COMPLEXES DU CUIVRE A PARTIR DE LIGANDS TRIPODAUX A SPHERE DE COORDINATION DE TYPE N3O. LES COMPLEXES RADICAL PHENOXYLE-CUIVRE ONT ETE ENGENDRES PAR OXYDATION ELECTROCHIMIQUE DES COMPLEXES PRECEDENTS. NOUS AVONS PU OBSERVER DES EFFETS DE LA STRUCTURE DU LIGANDS SUR L'ENVIRONNEMENT AUTOUR DU CUIVRE ET SUR LA STABILITE DES COMPLEXES RADICALAIRES CORRESPONDANTS.<br />DANS UN SECOND TEMPS, LA CHIMIE EN SOLUTION DES LIGANDS EN PRESENCE DE CUIVRE(I) OU (II), SOUS DES CONDITIONS AEROBIQUES OU ANAEROBIQUES, A ETE ETUDIEE AFIN DE MIMER ET COMPRENDRE LE PROCESSUS DE MATURATION DE L'ENZYME. UNE ETUDE PAR RMN DU FLUOR 19 A PERMIS D'APPORTER UNE CONTRIBUTION NOUVELLE A LA COMPREHENSION DE CETTE CHIMIE EN SOLUTION: DIFFERENTS TYPE DE MARQUAGE PAR LE FLUOR ONT ETE UTLILISES: MARQUAGE PAR F OU CF3 SUR UN PHENOL OU F SUR UNE QUINOLEINE.<br />DANS LA DERNIERE PARTIE, DES COMPLEXES DESTINES A STOCKER PLUS DE DEUX EQUIVALENTS OXYDANTS ONT ETE MIS AU POINT: POUR LE STOKAGE DE TROIS EQUIVALENT OXYDANTS, NOUS AVONS OBTENU LES DEUX PREMIERS COMPLEXES COMPORTANT UN RADICAL PHENOXYLE PONTANT DEUX IONS CUIVRIQUES

L'étude des mécanismes des transformations chimiques des composés organiques dans l'atmosphère exige de pouvoir mener des expériences en phase gazeuse dont les résultats peuvent être d'une part interprétables et d'autre part fiablement extrapolables aux conditions physico-chimiques de l'atmosphère. Ces deux contraintes impliquent donc de pouvoir s'affranchir de la complexité et de la variabilité de la composition atmosphérique et simultanément de pouvoir travailler dans des domaines de pression, de température et de concentrations proches de celles rencontrées dans l'atmosphère. La simulation expérimentale permet de remplir ces objectifs. Ce travail de doctorat porte donc sur la mise en œuvre de techniques de simulation atmosphérique expérimentale dans le cadre d'études de la réactivité du radical nitrate vis-à-vis de composés organiques volatils d'intérêt troposphérique. L'utilisation de cette méthode nous a conduit à développer une chambre de simulation atmosphérique. Des méthodes d'analyse par spectrométrie optique UV-visible (DOAS UV-visible) et infrarouge à transformées de Fourier (IRTF) à très long trajet optique ont été adoptées ce qui nous a conduit au développement d'un nouveau type de cellule multi-reflexion infrarouge stabilisée. Les résultats qui ont été obtenus portent sur l'étude des mécanismes d'oxydation initiés par NO3 vis-à-vis du formaldéhyde, de l'acétaldéhyde, du propionaldéhyde, du benzène et du toluène. Nos résultats ont permis de décrire complètement le schéma d'oxydation des aldéhydes et de déterminer les constantes cinétiques associées à ces espèces. Nos expériences ont aussi confirmé l'existence d'une réaction entre les radicaux peroxyacyles et NO3 et permis son étude sous conditions atmosphériques simulées. La discussion de son impact atmosphérique montre qu'il pourrait être considérable. Plus généralement, l'importance la chimie des radicaux nitrate vis-à-vis des espèces radicalaires secondaires apparaissant au cours du processus d'oxydation a été démontré. Le radical nitrate étant l'une des espèces-clefs de la troposphère nocturne, ces résultats intéressent la compréhension de l'évolution des polluants atmosphériques durant la nuit. Il résulte de ces recherches que l'utilisation d'une chambre de simulation, équipée de puissants moyens d'analyse spectrométrique in-situ, permet de mener des études mécanistiques avec des bilans complets ainsi que des études portant sur la génération et l'évolution de composés radicalaires intermédiaires.

<p>Possibly the most fascinating biochemical mechanism remaining to be solved is the formation of oxygen from water in photosystem II. This is a critical part of the photosynthetic reaction that makes solar energy accessible to living organisms.</p><p>The present thesis uses quantum chemistry, more specifically the density functional B3LYP, to investigate a mechanism where an oxyl radical bound to manganese is the active species in O-O bond formation. Benchmark calculations on manganese systems confirm that B3LYP can be expected to give accurate results. The effect of the self-interaction error is shown to be limited. Studies of synthetic manganese complexes support the idea of a radical mechanism. A manganese complex with an oxyl radical is active in oxygen formation while manganese-oxo complexes remain inactive. Formation of the O-O bond requires a spin transition but there should be no effect on the rate. Spin transitions are also required in many short-range electron-transfer reactions.</p><p>Investigations of the superproficient enzyme orotidine decarboxylase support a mechanism that involves an invariant network of charged amino acids, acting together with at least two mobile water molecules.</p>

<p>In today’s fast-changing and dynamic business environment, the pressures on manufacturing companies to compete on the global arena have been intensified. Production is challenged to handle and benefit from ever increasing competitions in terms of cost, delivery capability, and flexibility. In order to gain and sustain the competitive advantage under such circumstances, strong and constant development of production must be ensured not only with continuous improvements but also with radical improvements.</p><p>Continuous improvement or called Kaizen has been an established approach of production improvement. The concept of Kaizen is well described and many tools and methods that support Kaizen have been developed and widely applied in industry. However, for radical improvement or “Kaikaku” in Japanese, the need and the importance of Kaikaku are still limitedly recognized at companies. Moreover, the knowledge of structured support that facilitates an effective and efficient execution of Kaikaku has been insufficiently developed.</p><p>The purpose of the research presented in this thesis is to develop models and methods that address the need and the importance of Kaikaku in production and facilitate the realization of it.</p><p>The research consists of a literature study and three case studies. The literature study was conducted in order to structure the concept of Kaikaku. As a result of the study, a conceptual framework of Kaikaku was developed. The three case studies were conducted to identify influential factors to the realization of Kaikaku. Both Swedish and Japanese companies were studied and analyzed. These case studies led to identify a way of realizing a certain type of Kaikaku. Some characteristics of organization setting were also found influential to the realization of Kaikaku.</p><p>To conclude, the research has contributed to creating a foundation of the research area related to Kaikaku. This has opened up opportunities for further research in this field.</p>