Goals: Prepare a case study on the transition to the new OTC medicines groups with restrictions. To evaluate the positives and negatives, which brought the introduction of the group - with OTC restrictions. Pick up generally applicable principles and specify non-functional parts of the system. Method: For data processing method was applied theoretical research. Literature was searched in the database of the Czech National Library - Klementinum, WHO database, TRIBUNE and interfaces of News portals. The instrumental case study was processed for a detailed insight into the issues. The case study is also based on the analysis of the legal framework of the Czech Republic. The documents provided by SÚKL are used for financial analysis. As another method the stakeholder analysis was used - analysis of opinions of people involved in the drug policy. Results: The case study shows that switching medicines containing PSE to the limited group of OTC to prevent producers of drugs buing drugs in Czech pharmacies, but it did not reduce the amount of drugs produced in the country. Producers started to import precursors from abroad. The whole new system established in 2009 was correct in principle, but failed in practice. State Institute for Drug Control or other stakeholders in drug policy have not been able to resolve the ensuing complications.

No presente trabalho estudou-se a recristalização do aço de alta resistência baixa liga (ARBL) microligado ao nióbio (160 ppm em peso) da Companhia Siderúrgica Nacional 2336 utilizado na fabricação de reforços estruturais para a indústria automobilística. A grande utilização deste tipo de aço pelas indústrias tem motivado o desenvolvimento de novas ligas capazes de atender a requisitos críticos de estampagem combinado com alta resistência mecânica. Amostras deste aço no estado laminado a quente foram deformadas posteriormente a frio em escala piloto com reduções de 50 e 70%, reduções típicas na indústria, e recozidas em banho de sal em temperaturas variando entre 600 e 700ºC em diferentes tempos. A evolução microestrutural das amostras no estado encruado e na condição recozida foi acompanhada utilizando-se as técnicas de microscopia ótica e eletrônica de varredura. As texturas de deformação e de recristalização foram determinadas via difração de raios X. A fração volumétrica recristalizada (Xv) e o tamanho de grão foram determinados com o auxílio de metalografia quantitativa nas amostras recozidas. Medidas de microdureza Vickers foram utilizadas para construir as curvas de encruamento e da cinética de amolecimento em função da temperatura de recozimento e comparadas com curvas construídas pelo primeiro método. Os resultados mostram que a recristalização ocorre em temperaturas acima de 650°C. Com auxílio de um gráfico de Xv contra A (fração amolecida), podemos observar a ocorrência de um desvio da idealidade a 650°C e 700°C. A explicação mais provável é a ocorrência de precipitação, especialmente para o aço menos deformado. Os valores do expoente de Avrami obtidos a partir das duas abordagens (medidas de microdureza e metalografia quantitativa) são apresentados e discutidos. / The recrystallization of a high strength low alloy steel (HSLA) containing niobium (160 wt-ppm) was investigated. The HSLA steel, named CSN 2336, is used in the manufacture of structural parts for automotive industry. The increasing use of this application type of steels in automotive industries has motivated the development of new alloys able to gather the critical requirements for deep drawing combined with high strengths. Samples of this steel in hot-rolled condition were cold-rolled with reductions of 50% and 70%, commonly used in most of applications, and isothermally annealed in salt bath at temperatures between 600 and 700ºC. The microstructure of the samples in both coldworked and annealed states was imaged using light optical (LOM) and scanning electronic microscopies (SEM). Deformation and recrystallization textures were determined by X-ray diffraction. The recrystallized volume fraction (Xv) and the mean grain size were determined by quantitative metallography in the annealed samples. Vickers microhardness testing was used to determine the work hardening and the softening kinetics behaviors. The results show that recrystallization occurs at temperatures above 650°C for the most deformed steel. By plotting Xv against A (softening fraction), we observe the occurrence of a deviation from ideality at 650°C and 700°C, likely caused by solid-state precipitation, especially for the less deformed steel. The values of n (Avrami exponent) obtained from both approaches (softening curves and quantitative metallography) are presented and discussed.

Ce travail porte sur la synthèse, la caractérisation et l’évaluation en catalyse de réduction des protons en dihydrogène, de nouveaux complexes de Ni(II), Co(III), Cu(II) et Pd(II) basés sur des ligands de type thiosemicarbazone. La nature de l’espèce catalytique active a été étudiée par voltampérométrie cyclique et des propositions de mécanisme ont été formulés sur la base de calcul quantique de type DFT.Le premier chapitre introduit le contexte scientifique. Le second chapitre concerne la synthèse et la caractérisation des ligands de type N2S2 et des complexes mononucléaires associés de Ni, Cu et Pd. Le troisième chapitre présente la synthèse et la caractérisation de complexes binucléaires de Co et trinucléaire de Ni.Les études électrochimiques de ces complexes dans le DMF en présence d’une source de protons, nous a permis d’évaluer leur efficacité catalytique. Nos résultats montrent que les complexes du Cu et du Pd présentent une vague irréversible spécifique pour la réduction des protons, mais une décomposition est observée durant l’électrolyse. Par contre, les complexes de Ni et de Co ont montré une stabilité électrochimique ainsi que de bonnes performances catalytiques. En particulier, le nouveau complexe mononucléaire de Ni présente des propriétés catalytiques remarquables qui le classent parmi les meilleurs catalyseurs de la réduction des protons décrits dans la littérature. L’ensemble de ce travail fourni une description complète du comportement électrochimique des ligands de type N2S2 complexés à des métaux de transition. Il permet d’envisager des développements futurs dans l’amélioration des propriétés catalytiques de ces complexes. / This work focuses on the synthesis, the characterization and the catalytic evaluation in the reduction of protons into dihydrogen, of new complexes of Ni(II), Co(III), Cu(II) and Pd(II) based ligands Type thiosemicarbazone. The catalytically active species during the process of the proton reduction was studied by cyclic voltammetry and mechanisms were formulated on the basis quantum chemical calculation.The first chapter introduces the scientific context, the goals and the main objectives of this work. The second chapter concerns the synthesis and the characterization of the N2S2 ligands and their associated mononuclear complexes, Ni, Cu and Pd. The third chapter presents the synthesis and the characterization of binuclear Co and trinuclear Ni based on N2S2 ligand.Electrochemical studies of these complexes in DMF in the presence of a proton source (trifluoroacetic acid), allowed us to evaluate their catalytic efficiency. Our results show that Cu and Pd complexes have a specific irreversible wave for the reduction of protons, but decomposition is observed during electrolysis, which makes these uninteresting complexes for the reduction of protons.On the contrary, Ni and Co complexes showed an electrochemical stability and good catalytic performances. In particular, the new mononuclear Ni complex exhibits remarkable catalytic properties that rank it among the best catalysts for the reduction of protons reported in the literature. All this work provided a complete description of the electrochemical behavior of N2S2 thiosemicarbazone ligands complexed to transition metals. It allows considering future developments in improving the catalytic properties of these complexes.

<p>Hybrid density functional theory (DFT) B3LYP method is applied to study the four diverse enzyme systems: <i>zinc-containing peptidases</i> (thermolysin and stromelysin),<i> methyl-coenzyme M reductase</i>, <i>ribonucleotide reductases</i> (classes I and III), and <i>superoxide dismutases</i> (Cu,Zn- and Ni-dependent enzymes). Powerfull tools of modern quantum chemistry are used to address the questions of biological pathways at their molecular level, proposing a novel mechanism for methane production by methyl-coenzyme M reductase and providing additional insights into hydrolysis by zinc peptidases, substrate conversion by ribonucleotide reductases, and biological superoxide dismutation. Catalysis by these enzymes, with the exception of zinc peptidases, involves radical chemistry.</p>

Hybrid density functional theory (DFT) B3LYP method is applied to study the four diverse enzyme systems: zinc-containing peptidases (thermolysin and stromelysin), methyl-coenzyme M reductase, ribonucleotide reductases (classes I and III), and superoxide dismutases (Cu,Zn- and Ni-dependent enzymes). Powerfull tools of modern quantum chemistry are used to address the questions of biological pathways at their molecular level, proposing a novel mechanism for methane production by methyl-coenzyme M reductase and providing additional insights into hydrolysis by zinc peptidases, substrate conversion by ribonucleotide reductases, and biological superoxide dismutation. Catalysis by these enzymes, with the exception of zinc peptidases, involves radical chemistry.

The lumen-to-cell transport, cellular accumulation, and toxicity of ionic cadmium (109Cd2+) and cadmium-cysteine conjugate (Cys-S-109Cd-S-Cys) were studied in isolated perfused S2 segments of the proximal tubule of the rabbit kidney. All perfusion solutions were HEPES buffered and contained 3H-L-glucose which functioned as a volume and leak marker along with 250 nM FD & C Green dye as a vital dye. When ionic cadmium, 0.73µM Cd2+, or 0.73µM cadmium-cysteine conjugate (Cys-S-109Cd-S-Cys) containing solution was perfused through the lumen of the tubule there was no visual evidence of toxicity such as blebbing of the luminal membrane, cellular vital dye uptake, and cellular swelling. Ionic Cd2+ transport was temperature dependent (87% reduction at 22°C and 100% at 11°C) and inhibited by FeCl2 (42% reduction at 10µM) and ZnCl2 (48% reduction at 20µM), and high Ca2+ concentrations (27% reduction at 1.95mM and 69% at 2.6mM). The ionic Cd2+ transport was not affected by verapamil and diltiazem. The cadmium conjugate (Cys-S-Cd-S-Cys) transport was also temperature dependent (76% reduction at 22°C and 100% at 11°C) and inhibited by the amino acids L-cystine and L-arginine (55% and 50% respectively), stimulated by L-methionine (56%), but not affected by L-aspartate, L-glutamate and Gly-Sar. 2, 3-Dimercaptopropane-1-Sulfonate (DMPS) co-perfused with Cd2+ decreased absorption of 20µM Cd2+ (39% reduction at 30 µM and 94.6% reduction at 200 µM), while DMPS added to the bathing solution has no effect on the luminal transport of Cd2+. DMPS co-perfused with 20 µM Cys-S-Cd-S-Cys substantially reduced Cd2+ transport (62% reduction at 30 µM). We conclude that cadmium can be transported at the luminal membrane of the S2 segment of the proximal tubule by multiple mechanisms, depending on the form which it is presented to membrane. Ionic cadmium appears to be transported by iron (DCT1), zinc (ZTL1) transporters and some kind of calcium-selective channel while cadmium conjugate of L-cysteine appears to be transported by L-cystine transporters (system b0+). Dipeptide transporter is not involved in the transport of cadmium. DMPS appears to be a chelator for cadmium.

Les rétrovirus sont des virus à ARN, enveloppés présents dans de nombreuses espèces animales de rente, chez les animaux de compagnie et chez l'homme. Une des particularités des rétrovirus concerne l'intégration du génome viral au sein du génome de la cellule infectée; cette intégration est réalisée par une enzyme virale, l'intégrase. Le projet de cette thèse vise à mieux comprendre le fonctionnement de cette enzyme notamment en identifiant des facteurs cellulaires interagissant avec celle-ci, facteurs qui pourraient être des agents favorisant le processus intégratif ou, au contraire, des agents restrictifs. Les intégrases de deux modèles de rétrovirus ont été utilisées dans cette étude : L'intégrase de RAV1, un rétrovirus exogène aviaire du genre des alpharétrovirus appartenant au sous-groupe A de la famille des ASLV. Cette enzyme virale est largement étudiée soit au niveau structural ou fonctionnel, mais les données concernant ses partenaires cellulaires sont rares et insuffisantes. La seconde intégrase est celle du PERV A/C, un rétrovirus endogène porcin du genre gammarétrovirus. Aucune information sur cette enzyme n'a été décrite jusqu'à présent. Ces deux enzymes, en fusion avec une étiquette 6xHistidine, ont été donc produites en bactérie, et en cellules d'insecte puis purifiées sur colonne d'affinité en FPLC. Leurs activités catalytiques ont été testées in vitro. Ces tests permettent de valoriser la capacité de l'intégrase à exercer principalement les 2 fonctions dont elle est responsable in vivo, le clivage en 3' et le transfert de brins, et une activité qu'elle exerce exclusivement in vitro, la désintégration. Les protéines pures et actives ont ensuite servies à la vérification de leur interaction avec une protéine cellulaire, Brd2. La technique 'Far western blot' a ainsi permis de valider l'interaction entre l'intégrase de PERV et la protéine cellulaire, puis d'identifier les domaines de l'intégrase et de Brd2 impliqués dans cette interaction. A terme, l'identification de ce facteur cellulaire et la validation de son rôle dans le processus intégratif permettront de mieux comprendre ce processus particulier développé par les rétrovirus et pourront conduire au développement d'inhibiteurs dirigés contre cette interaction

Polycyclic aromatic hydrocarbons (PAHs) and nitrogen-containing polycyclic aromatic compound (N-PAC) are widespread toxic pollutants in environments. The fate of PAHs and N-PACs are of great concern because some of these compounds were identified as caricinogenic, mutagenic and teratogenic compounds. As described in literature, dissolved organic matter (DOM) is an important factor in control of their fate; however, the binding behaviors between these compounds and DOM are still not fully understood. The binding constants (KDOC) between humic substances and one selected N-PAC, benzo[h]quinoline, were measured at varying pH levels using fluorescence quenching (FQ) method. As fluorescence characteristics of benzo[h]quinoline change with pH, determination required two optimum sets of excitation and emission wavelength pairs. A simple mixing model was proposed and used to eliminate the inherent fluorescence interference between benzo[h]quinoline (BQ) and its protonated form, benzo[h]quinolinium (BQH+), and to deduce Kmix which represents the overall binding as the sum of that for the individual analogs. The characteristics of humic substances, especially their hydrophobicity and aromaticity, established by principal components analysis of structural and elemental compositions, were the main determinants of their binding affinity with both benzo[h]quinoline and benzo[h]quinolinium (KBQ and KBQH+) across a range of pH values. Hydrophobic interaction is likely to control the binding between humic substance and benzo[h]quinoline and benzo[h]quinolinium, in lower and higher pH ranges (pH<3, pH>6). In contrast, cation exchange seems to control on the binding affinity of benzo[h]quinolinium in the middle range of pH. Determination of PAH concentration is quite essential for investigating the fate of PAHs in environments. Microwave-assisted headspace solid-phase microextraction (MA-HS-SPME) with a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was applied as a single step prior to determination of PAH concentrations in water using GC-MS. To optimize the extraction efficiency of PAHs by MA-HS-SPME, the influence of various parameters, including temperature, duration of thermal desorption, microwave irradiation power and duration, and the temperature of the circulating cooling water system, was studied. The proposed method was demonstrated applicable to environmental water samples. In addition, DOM matrix effect did not influence the determination and extraction efficiency of PAHs. Although the proposed simple mixing model can eliminate the fluorescent interference of hydrophobic organic compounds with acid-base pair forms, it is still limited in using for correcting the KDOC measurement of more than two fluorescent compounds simultaneously. A new alternative protocol, complexation-flocculation combined with MA-HS-SPME/GC-MS method, was proposed to determine the binding constants of seleted PAHs to humic substances. The results obtained are comparable with KDOC data reported in literatures. CF-MA-HS-SPME/GC-MS provides some advantages over other methods, such as applicable not limited to fluorescent compounds, faster in determination and capable in measuring varieties of compounds simultaneously.

Neighboring northern Kaohsiung with a dense population of petrochemical and petroleum industrial complexes included China Petroleum Company (CPC) refinery plant, Renwu and Dazher petrochemical industrial plants. In recent years, although many scholars have conducted regional studies, but are still limited by the lack of relevant information evidences (such as odorous matters identification and VOCs fingerprint database), while unable to clearly identify the causes of poor ambient air quality. By sampling and analyzing VOCs, we will be able to understand the major sources of VOCs in northern Kaohsiung and their contribution, and to provide the air quality management and control countermeasures for local environmental protection administration. In this study, we sampled and analyzed the speciation of VOCs and sulfur-containing odorous matters (SOMs) in the CPC refinery plants, Renwu and Dazher petrochemical complexes simultaneously with stack sampling. The sampling of VOCs and SOMs were conducted on January 7th, 14th, and 19th, 2011 (dry season) and May 6th, 13rd, and 23rd, 2011 (wet season). We established the emission source database, investigated the characteristics of VOC fingerprints, and estimate the emission factor of each stack. It helps us understand the temporal and spatial distribution of VOCs and ascertain major sources and their contribution of VOCs. Major VOCs emitted from the stacks of the CPC refinery plant were toluene and acetone. It showed that petroleum refinery processes had similar VOCs characteristics and fingerprints. The fingerprints of stack emissions at Renwu and Dashe industrial complexes varied with their processes. Hydrogen sulfide was the major sulfur-containing odorous matter in all petrochemical plants. Compared to other petrochemical complexes, Renwu industrial complex emitted a variety of SOMs species as well as relatively high concentrations of sulfur-containing odorous matters. The petrochemical industrial complexes in the industrial ambient of VOCs analysis results showed that isobutane, butane, isopentane, pentane, propane of alkanes, propene of alkenes, toluene, ethylbenzene, xylene, styrene of aromatics, 2-Butanone (MEK), acetone, of carbonyls are major species of VOCs. In addition, ethene+acetylene+ethane (C2), 1,2-dichloroethane, chloromethane, dichloromethane, MTBE were also occasionally found. Sulfur-containing odorous matter (SOMs) analytical results showed that major odorous matters included hydrogen sulfide, methanethiol, dimethyl sulfide, and carbon disulfide. The highest hydrogen sulfide concentration went up to 5.5 ppbv. In this study, the species of VOCs were divided into alkanes, alkenes, aromatics, carbonyls, and others. The temporal and spatial distribution of various types of VOCs strongly correlated with near-surface wind direction. The most obvious contaminants were alkanes, aromatics, and carbonyls of the dispersion to the downwind. Generally, the ambient air surrounding the petrochemical industrial complexes was influenced by various pollutants in the case of high wind speeds. It showed that stack emission and fugitive sources had an important contribution to ambient air quality. TSOMs and hydrogen sulfide emitting mainly from local sources resulted in high concentration of TSOMs and hydrogen sulfide surrounding the petrochemical industrial complex. Principal component analysis (PCA) results showed that the surrounding areas of petrochemical industrial complexes, regardless of dry or wet seasons, were mainly influenced by the process emissions and solvent evaporation. The impact of traffic emission sources ranked the second. Chemical mass balance receptor modeling showed that stack emissions from the CPC refinery plants contributed about 48 %, while fugitive emission sources and mobile sources contributed about 30 % and 11%, respectively. The stack emissions from Renwu industrial complex contributed about 75 %, while fugitive emission sources and mobile sources contributed about 17 % and 5 %, respectively. The stack emissions from Dazher industrial complex contributed about 68 %, while fugitive emission sources and mobile sources contributed about 21 % and 2 %, respectively.

A new class of &pi / -conjugated monomers was synthesized with combination of electron donating and electron-withdrawing heterocyclics to understand the effects of structural differences on electrochemical and optoelectronic properties of the resulting polymers. Electron deficient benzotriazole, substititued with benzyl from two available sites, coupled with stannylated electron donating groups, ethylenedioxythiophene (EDOT) and thiophene (Th), to yield four different monomers / 1-benzyl-4,7-di(thiophen-2-yl))-2H-benzo[d][1,2,3] triazole (BBTA), 2-benzyl-4,7-di(thiophen-2-yl))-2H-benzo[d][1,2,3] triazole (BBTS), 1-benzyl-4,7-bis(2,3-dihydrothieno[3,4-b]dioxin-5-yl)-2H-benzo [d][1,2,3]triazole (BBTEA), 2-benzyl-4,7-bis(2,3-dihydrothieno[3,4-b]dioxin-5-yl)-2H-benzo [d][1,2,3]triazole (BBTES). Furthermore, EDOT and thiophene terminated napthalene-2,3-crown ether containing monomers, 14,19-di(thiophen-2-yl)-naphtho[2,3-b][1,4,7,10,13] pentaoxacyclo pentadecane (TNCT), 14,19-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-naphtho[2,3-b][1,4,7,10,13]pentaoxacyclopenta decane (ENCE), were synthesized to observe the effect crown ether moiety on the final electrochemical and optoelectronic properties of resultant polymers. Cyclic voltammetry, UV-Vis-NIR spectroscopy and colorimetry techniques were employed to examine electrochemical and optoelectronic properties of all monomers and polymers. Experimental results showed that alteration of substituent, substitution position and donor groups&rsquo / strength lead to obtain polymers with different redox behaviors, optical band gaps and different number of achievable colored states.