Deux phénomènes liés au TFIIH ont été étudiés : l'influence des mutations spécifiques dans la sous-unité XPD de TFIIH sur la réponse transcriptionnelle de certains gènes après l'irradiation UV, et l'interaction entre le TFIIH et la transcription des gènes de classe III. Une analyse détaillée de la dynamique du transcriptome a été effectuée pour la réponse des cellules humaines mutantes XP-D/CS à l'UV. Il a été démontré que la dysrégulation sélective observée de l’expression des gènes était liée à l'incapacité pour la ré-initiation transcriptionnelle et à l'hétérochromatinisation suivante, où l'histonedésacétylase SIRT1 a été identifiée comme le principal facteur. Son inhibition a permis de recouvrer l'expression normale d'un nombre substantiel des gènes affectés. Une étude de la participation pangénomique du coeur de TFIIH dans latranscription a découvert son association avec les gènes actifs de classe III. Cette association a été démontrée être indépendante de Pol II. Le coeur de TFIIH a été montré participer directement à la transcription effectuée in vitro par Pol III. / In this work, two TFIIH-related phenomena were investigated : the influence of specific mutations in TFIIH XPD subunits on the transcriptional response of different genes on UV irradiation and the interaction between TFIIH and transcription of class III genes. For the first time the detailed investigation of transcriptome dynamics was carried out for the response of XP-D/CS mutant human cells to UV-irradiation. The transcription regulation nature of the observed selective gene expression dysregulation was clearly observed. Its relation to failure of transcription re-initiation and consequentheterochromatisation was demonstrated. SIRT1 histone deacetylase was identified as the main driver of the repressive chromatin establishment on the certain genes upon UV. Inhibition of SIRT1 was found to recover normal expression of substantial number of affected genes. SIRT1 mediated mechanism was shown to be XP-D/CS specific. A potential link between this longevity related protein and progeria features of XP-D/CS mutants was hypothesised. Genome-wide study of the involvement of the core TFIIH in transcription revealed its association with active class III genes, not described previously. This association was demonstrated to be Pol II-independent. The core TFIIH was shown to be directly involved in Pol III mediated transcription in vitro.

<p>Uzorci zemlji&scaron;ta iz pov&scaron;inskog sloja dubine 0 - 10 cm<br />prikupljeni su sa 121 lokacije na gradskom području Novog<br />Sada. Ispitivano područje obuhvatilo je povr&scaron;inu (4 x 5)km²,<br />koja je podeljena na mrežna polja veličine (400 x 400) m^2&nbsp;i u&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<br />svakom polju uzet je po jedan uzorak. Za 121 uzorak<br />gradskog zemlji&scaron;ta Novog Sada ispitana su fizičko-hemijska<br />svojstva zemlji&scaron;ta, ukupni i pristupačni sadržaj metala (As,<br />Co, Cr, Cu, Mn, Ni, Pb, Zn) i njihova prostorna raspodela.<br />Konturne mape prostorne raspodele metala u zemlji&scaron;tu<br />dobijene su kori&scaron;ćenjem interpolacijske metode običnog<br />kriginga. Za pojedine uzorke izvr&scaron;eno je razdvajanje čestica<br />po veličinama frakcionisanjem u vodi pomoću sita različitih<br />veličina i identifikovani su minerali prisutni u frakciji prah +<br />glina. Aktivnosti radionuklida &bdquo;unsupported&rdquo;²¹⁰Pb i ¹³⁷Cs<br />određene su za jedan deo uzoraka zemlji&scaron;ta u Novom Sadu i<br />za uzorke zemlji&scaron;ta pored fabrike akumulatora u Somboru.<br />Ispitana je i vertikalna distribucija stabilnog i radioaktivnog<br />Pb u zemlji&scaron;tu.</p><p>Na 14 lokacija u Novom Sadu prikupljeno je 35 uzoraka<br />snega direktno sa asfaltnih puteva i sa zemljanih povr&scaron;ina u<br />okolini puteva i na pe&scaron;ačkim ostrvima. Raspodela čestica po<br />veličinama i ukupne koncentracije metala (Al, Ca, Cu, Fe, K,<br />Na, Mn, Ni, Pb, Zn) određene su analizom filtriranih uzoraka,<br />a za 4 uzorka ispitana je morfologija čestica i urađena<br />semikvantitativna analiza čestica u suvoj materiji.</p><p>Prilikom obrade rezultata merenja primenjene su metode<br />deskriptivne statistike i multivarijacione statističke analize u<br />cilju identifikacije izvora zagađenja i određivanja povezanosti<br />između samih metala i drugih parametara.</p> / <p>A total of 121 surface soil samples were collected&nbsp;across the central part of Novi Sad covering a surface&nbsp;area (4 km x 5 km). The physicochemical properties,&nbsp;pseudo total and available metal concentrations (As,&nbsp;Co, Cr, Cu,&nbsp; Mn, Ni, Pb, and Zn) were determined.&nbsp;Contour maps of spatial distribution of the investigated&nbsp;metals were obtained using ordinary&nbsp; kriging&nbsp;interpolation method. Separation of different particle&nbsp;<br />size fractions by wet sieving&nbsp; and identification of&nbsp;minerals in the clay and silt fraction for some soil&nbsp;samples were performed.&nbsp; Specific activities of&nbsp;radionuclides &ldquo;unsupported&rdquo; ²¹⁰Pb and ¹³⁷Cs were&nbsp;measured in forty soil samples collected in urban area&nbsp;of Novi Sad and industrial area of Sombor (near a&nbsp;battery manufacturer).&nbsp; Vertical distribution of stable and&nbsp;radioactive&nbsp; Pb for&nbsp; two samples from the industrial soil&nbsp;was examined.</p><p>Thirty five snow samples were collected at fourteen&nbsp;locations near crossroads in Novi Sad. The samples&nbsp;were taken directly from the road surface and from the&nbsp;ground surface in the vicinity of roads and on&nbsp;pedestrian islands. Particle size distribution and &nbsp;total&nbsp;concentration of the metals (Al, Ca, Cu, Fe, K, Na, Mn,&nbsp;Ni, Pb, Zn) were &nbsp;determined for filtered samples. Semi-quantitative analysis of the particles was &nbsp;conducted and&nbsp;morphology of the particles was examined for dry&nbsp;matter of four snow samples.&nbsp;</p><p>Methods of descriptive and multivariate statistics and&nbsp;geostatistics were carried out for &nbsp;the analysis and&nbsp;interpretation of the data.</p>

Interstitial brachytherapy using permanent seeds is a common modality for the treatment of early stage prostate cancer. It consists of inserting hundreds of radioactive seeds (size of a grain of rice) in the prostate by means of transperineal needles. In this procedure, dose delivery to healthy surrounding organs at risk (OAR) and dose homogeneity within the prostate are of prime concern. Placement errors should therefore be minimized to avoid unacceptable area underdosage or overdosage. At present, brachytherapy seeds can be loaded with three different radionuclides: iodine-125 (¹²⁵I: 28.37 keV; 59.40 days), palladium-103 (¹⁰³Pd: 20.74 keV; 16.991 days), and cesium-131 (¹³¹Cs: 30.45 keV; 9.689 days). Long or short term morbidity is the main drawback of ¹²⁵I and ¹³¹Cs due to their deeper penetration in the normal tissues. However, both provide a good homogeneity of the dose distribution within the prostate. By contrast, ¹⁰³Pd offers a short penetration depth that reduces the dose to OAR. Nevertheless, it could result in cold spot (underdosage) where a recurrence of the cancer could appear. A compromise had to be found between good implant uniformity and low dose to OAR. We propose therefore to study if the combination of two radionuclides inside the same seed could be a solution. Two mixtures were considered: ¹⁰³Pd_0.75-¹²⁵I_0.25 and ¹⁰³Pd_0.25-¹³¹Cs_0.75. The subscripts denote the fractions of internal activity of each radionuclide. The work is subdivided into three steps. First we adapt the AAPM TG-43U1 dosimetry formalism used by the physician to make multiple-radionuclides sources compatible with Treatment Planning Systems (TPS). Then the dose distributions around the bi-radionuclide seeds are determined. Second, the prescription doses for both sources are derived using the linear quadratic model for tumor cell surviving fraction. They were computed using mono-radionuclide implants as benchmarks. Finally, treatment plans and Dose-Volume Histograms parameters have been computed on real patients virtually implanted with bi-radionuclide seeds and the results were compared with the mono-radionuclide one. These parameters can then be used to evaluate the Normal Tissue Complication Probability (NTCP) of urethra, the most exposed organ at risk in prostate brachytherapy. First, dosimetry results show that, from a pure physical point of view (i.e. without tissue reponse), the dose distributions of both mixtures lies in between that for ¹⁰³Pd and ¹²⁵I/¹³¹Cs. The compromise between homogeneity and reduced dose at large distance can be reached. Second, the averaged prescription doses for the Pd-I mixture are 142⁺¹⁵_-16Gy and 142⁺⁶_-8Gy using ¹⁰³Pd and ¹²⁵I as benchmarks, respectively. The values for the Pd Cs mixture are 128⁺¹³_-13Gy and 115⁺⁶_-7Gy, using ¹⁰³Pd and ¹³¹Cs, respectively, as benchmarks. Finally, urethral NTCP results fall in the 19 to 23% range. However, they are affected by large uncertainties, making the comparison difficult. At present, no conclusion could be drawn about the efficiency of bi-radionuclide brachytherapy in comparison with mono-radionuclide using the available models. Permanent seed prostate brachytherapy suffers a lot from the lack of precision on radiobiological modelling parameters. A better knowledge of their values could significantly improve the predicting models and therefore lead to better treatment outcome.

This thesis deals with the design and synthesis of ligands for asymmetric catalysis: palladium catalyzed allylic alkylations, and rho-dium and iridium catalyzed hydrogenations of olefins. Chirally flexible phosphepine ligands based on biphenyl were synthesized and their properties were studied. The rotation barrier for configurationally flexible phosphepines was determined by NMR spectroscopy. The ratio of the atropisomers was shown to depend on the group bound to phosphorus. Only complexes with two homochiral ligands bound to the metal center were observed upon complexation with Rh(I). It was shown that one diastereomer of the flexible ligand exhibits higher activity but lower selectivity than its diastereomer in the rhodium catalyzed hydrogenation of methyl alfa-acetamidocinnamate. These ligands were also tested in nickel catalyzed silabora-tions. Chiral P,N-ligands with pseudo-C2 and pseudo-CS symmetry based on pyrrolidines-phospholanes or azepines-phosphepines were synthesized and studied in palladium catalyzed allylic alkylations. Semi-flexible azepine-phosphepine based ligands were prepared and their ability to adopt pseudo-C2 or pseudo-CS symmetry depending on the substrate in allylic alkylations was studied. It was shown on model allyl systems with flexible N,N-ligands that the ligand prefers CS-symmetry in compexes with anti-anti as well as syn-syn allyl moieties, but that for the latter type of complexes, according to computations, the configuration of the ligand is R*,R* in the olefin complexes formed after addition of a nucleophile to the allylic group. A preliminary investigation of the possibilities to use a su-pramolecular approach for the preparation of P,N-ligands with pseudo-C2 and pseudo-S symmetry was made. An N,N-ligand with C2 symmetry was prepared and its activity in palladium catalyzed ally-lic alkylation was studied. Pyridine-based P,N-ligands were tested in iridium catalyzed hy-drogenations of unfunctionalized olefins with good activities and se-lectivities. In order to attempt to improve the selectivity, ligands with a chirally flexible phosphepine fragment were prepared and applied in catalysis with promising results. / QC 20100929

The global marketplace today encompasses 6 billion people. Many companies are beginning to see themselves as international rather than national acting on a global arena. An essential aspect of going abroad is to know where to go and why to go there. In order to be able to analyze a foreign market a company needs to do market research in the foreign market as to gather essential information. A firm which is facing a quick internationalization process is the Swedish direct sales firm of cosmetics Oriflame. Oriflame has grown quickly in developing countries but is not present in one of the biggest market for direct sales in Europe: France. The purpose of this thesis is to develop a theoretical framework to analyze foreign markets and apply it to the French market of direct sales in cosmetics and Oriflame. A qualitative study based on the 5 Cs framework for analyzing foreign markets has been carried out. Seven focus groups have been conducted in France and Sweden in order to obtain information about and comparability in consumer attitudes towards Oriflame’s marketing mix. Interviews have been conducted in order to get information about Oriflame as a company. Secondary data has been gathered from different sources for the theoretical framework as well as for the empirical research on issues such as culture, competition and market. This thesis has developed a theoretical framework to analyze foreign markets called the 5 Cs. The 5 Cs are based on: Company, Constitution, Competition, Customers and Culture. The 5 Cs is a very general framework and can be applied to a wide range of foreign markets and firms and was in this case applied to analyze a real world case of Oriflame and France. The analysis of the empirical findings found that there is potential for Oriflame to enter the French market in terms of consumer preferences and general market characteristics. However, it also found that what will probably determine everything in the end is whether Oriflame can be strategically committed to enter a mature West European market like France.

<p>The global marketplace today encompasses 6 billion people. Many companies are beginning to see themselves as international rather than national acting on a global arena. An essential aspect of going abroad is to know where to go and why to go there. In order to be able to analyze a foreign market a company needs to do market research in the foreign market as to gather essential information. A firm which is facing a quick internationalization process is the Swedish direct sales firm of cosmetics Oriflame. Oriflame has grown quickly in developing countries but is not present in one of the biggest market for direct sales in Europe: France.</p><p>The purpose of this thesis is to develop a theoretical framework to analyze foreign markets and apply it to the French market of direct sales in cosmetics and Oriflame.</p><p>A qualitative study based on the 5 Cs framework for analyzing foreign markets has been carried out. Seven focus groups have been conducted in France and Sweden in order to obtain information about and comparability in consumer attitudes towards Oriflame’s marketing mix. Interviews have been conducted in order to get information about Oriflame as a company. Secondary data has been gathered from different sources for the theoretical framework as well as for the empirical research on issues such as culture, competition and market.</p><p>This thesis has developed a theoretical framework to analyze foreign markets called the 5 Cs. The 5 Cs are based on: Company, Constitution, Competition, Customers and Culture. The 5 Cs is a very general framework and can be applied to a wide range of foreign markets and firms and was in this case applied to analyze a real world case of Oriflame and France. The analysis of the empirical findings found that there is potential for Oriflame to enter the French market in terms of consumer preferences and general market characteristics. However, it also found that what will probably determine everything in the end is whether Oriflame can be strategically committed to enter a mature West European market like France.</p>

Cette thèse est consacrée au problème de la reconnaissance visuelle des objets basé sur l'ordinateur, qui est devenue un sujet de recherche très populaire et important ces dernières années grâce à ses nombreuses applications comme l'indexation et la recherche d'image et de vidéo , le contrôle d'accès de sécurité, la surveillance vidéo, etc. Malgré beaucoup d'efforts et de progrès qui ont été fait pendant les dernières années, il reste un problème ouvert et est encore considéré comme l'un des problèmes les plus difficiles dans la communauté de vision par ordinateur, principalement en raison des similarités entre les classes et des variations intra-classe comme occlusion, clutter de fond, les changements de point de vue, pose, l'échelle et l'éclairage. Les approches populaires d'aujourd'hui pour la reconnaissance des objets sont basé sur les descripteurs et les classiffieurs, ce qui généralement extrait des descripteurs visuelles dans les images et les vidéos d'abord, et puis effectue la classification en utilisant des algorithmes d'apprentissage automatique sur la base des caractéristiques extraites. Ainsi, il est important de concevoir une bonne description visuelle, qui devrait être à la fois discriminatoire et efficace à calcul, tout en possédant certaines propriétés de robustesse contre les variations mentionnées précédemment. Dans ce contexte, l'objectif de cette thèse est de proposer des contributions novatrices pour la tâche de la reconnaissance visuelle des objets, en particulier de présenter plusieurs nouveaux descripteurs visuelles qui représentent effectivement et efficacement le contenu visuel d'image et de vidéo pour la reconnaissance des objets. Les descripteurs proposés ont l'intention de capturer l'information visuelle sous aspects différents. Tout d'abord, nous proposons six caractéristiques LBP couleurs de multi-échelle pour traiter les défauts principaux du LBP original, c'est-à-dire, le déffcit d'information de couleur et la sensibilité aux variations des conditions d'éclairage non-monotoniques. En étendant le LBP original à la forme de multi-échelle dans les différents espaces de couleur, les caractéristiques proposées non seulement ont plus de puissance discriminante par l'obtention de plus d'information locale, mais possèdent également certaines propriétés d'invariance aux différentes variations des conditions d'éclairage. En plus, leurs performances sont encore améliorées en appliquant une stratégie de l'image division grossière à fine pour calculer les caractéristiques proposées dans les blocs d'image afin de coder l'information spatiale des structures de texture. Les caractéristiques proposées capturent la distribution mondiale de l'information de texture dans les images. Deuxièmement, nous proposons une nouvelle méthode pour réduire la dimensionnalité du LBP appelée la combinaison orthogonale de LBP (OC-LBP). Elle est adoptée pour construire un nouveau descripteur local basé sur la distribution en suivant une manière similaire à SIFT. Notre objectif est de construire un descripteur local plus efficace en remplaçant l'information de gradient coûteux par des patterns de texture locales dans le régime du SIFT. Comme l'extension de notre première contribution, nous étendons également le descripteur OC-LBP aux différents espaces de couleur et proposons six descripteurs OC-LBP couleurs pour améliorer la puissance discriminante et la propriété d'invariance photométrique du descripteur basé sur l'intensité. Les descripteurs proposés capturent la distribution locale de l'information de texture dans les images. Troisièmement, nous introduisons DAISY, un nouveau descripteur local rapide basé sur la distribution de gradient, dans le domaine de la reconnaissance visuelle des objets. [...]

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-02-25T13:31:28Z No. of bitstreams: 1 Tese Uenderson Araujo Barbosa -final.pdf: 2006362 bytes, checksum: 7f8502d02bb06b7f75032fb7a79d79bc (MD5) / Approved for entry into archive by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-05-10T17:54:24Z (GMT) No. of bitstreams: 1 Tese Uenderson Araujo Barbosa -final.pdf: 2006362 bytes, checksum: 7f8502d02bb06b7f75032fb7a79d79bc (MD5) / Made available in DSpace on 2016-05-10T17:54:24Z (GMT). No. of bitstreams: 1 Tese Uenderson Araujo Barbosa -final.pdf: 2006362 bytes, checksum: 7f8502d02bb06b7f75032fb7a79d79bc (MD5) / CAPES e CNPq / Neste trabalho foram propostas estratégias analíticas visando à avaliação toxicológica de metais e metaloides em medicamentos utilizados no tratamento da anemia ferropriva, empregando técnicas cromatográficas e não cromatográficas. Na primeira parte desta tese determinou-se chumbo nos medicamentos aplicando espectrometria de absorção atômica com atomização eletrotérmica (ETAAS). O preparo da amostra foi realizado fazendo uso de digestão ácida em bloco digestor com sistema de refluxo “dedo frio” usando 3 mL de HNO3 (69% v/v) e 1 mL de H2O2 (30% v/v). Foram otimizadas as temperaturas de pirólise e atomização usando uma mistura de paládio e magnésio como modificador químico convencional, obtendo-se 1100ºC e 2000ºC para pirólise e atomização, respectivamente. Com uma massa característica de 21,3 pg e 0,25 e 0,82 µg L-1, para os limites de detecção (LD) e de quantificação (LQ), respectivamente. A precisão, expressa pelo desvio padrão relativo de 5.92% para uma amostra com concentração de chumbo igual a 2,98 µg g-1. A exatidão foi estimada por comparação entre os resultados obtidos por ETAAS e espectrometria de massas com plasma indutivamente acoplado (ICP-MS). As concentrações de chumbo nas amostras variaram entre 0,096 e 7,068 µg g-1. Na segunda parte deste trabalho, foi efetuada a determinação de mercúrio através de amostragem em suspensão e espectrometria de absorção atômica com alta resolução e fonte contínua com geração de vapor frio (HR-CS CVAAS). As condições ótimas de preparo das suspensões (1,5 mol L-1 de HCl, 1,25% (m/v) de tioureia e 15 minutos de sonicação) foram otimizadas por planejamento fatorial completo. Os limites de detecção e quantificação foram 0,63 ng g-1 e 2,11 ng g-1, respectivamente. O desvio padrão relativo para avaliação da precisão foi calculado usando duas amostras com concentrações 4,82 e 9,61 ng g-1 com resultados 10,89 e 6,84%, respectivamente. Foi estimada a possível perda de mercúrio durante o procedimento proposto e a exatidão, mediante testes de adição e recuperação, variando entre 85,0 e 106,0%. As concentrações de mercúrio ficaram entre 3,17 e 34,86 ng g-1. A terceira parte deste trabalho descreve a determinação de macro e microelementos e o estudo in vitro da bioacessibilidade de ferro em medicamentos usados no tratamento da anemia ferropriva. Foi escolhida a espectrometria de emissão ótica com plasma indutivamente acoplado (ICP OES) como técnica analítica de medida. Foi efetuada digestão ácida para tratamento das amostras e o método foi validado, demonstrando boa sensibilidade, com limites de quantificação (mg L-1) 0,52 para Ca, 0,14 para K, 0,03 para Mg, 0,07 para Mn, 0,40 para Na, 0,36 para P e 0,24 para Zn. A precisão do método foi reconhecida mediante experimentos repetitivos intradia e interdia com resultados abaixo de 20%. Durante estudo da exatidão, testes de adição e recuperação foram executados em diferentes concentrações com resultados entre 81,85 e 114,97%. A robustez do plasma foi calculada mediante uma razão entre as linhas iônica e atômica de magnésio, Mg(II)/Mg(I) e os resultados, mediante análise componentes principais (PCA) e análise por agrupamentos hierárquicos (HCA). O estudo de bioacessibilidade in vitro de Fe demonstrou que alguns medicamentos são melhores bioacessíveis, sendo portanto, mais recomendados para o tratamento da anemia, comprovando dados da literatura farmacológica. Na quarta parte deste trabalho descreve-se o estudo da determinação e especiação simultânea de arsênio e cromo por 11 cromatografia líquida de alta eficiência acoplada à ICP-MS (HPLC-ICP-MS). A determinação total de arsênio e cromo foi realizada usando uma digestão ácida em forno de micro-ondas, uma mistura de 4 mL HNO3 (69% v/v) e 1 mL de H2O2 (30% v/v) e análise por ICP-MS. Para o estudo de especiação foi elaborado um estudo com três possíveis procedimentos para extração das espécies, sendo selecionado um procedimento com água a 80ºC por 30 minutos em energia de micro-ondas. Usando uma fase móvel contendo 1,0 mM de hidróxido de tetrabutilamônio (TBAH), 0,7 mM de ácido etilenodiaminotetracético (EDTA) e 5% de metanol (v/v) em pH 7,2 foi possível separar as espécies presentes com tempo de retenção de 5 minutos com separação de As(III), As(V), Cr(III) e Cr(VI), com limites de detecção de 0,002, 0,003, 0,140 e 0,042 µg g-1, respectivamente. A exatidão do método foi avaliada conforme testes de adição e recuperação, entre 80,64 e 109,36%. O método foi aplicado em amostras do Brasil e Espanha, com concentrações entre 0,1-1,3 e 0,18-62,27 µg g-1 para As e Cr, respectivamente. / In this thesis work analytical strategies have been proposed for toxicological assessment of metals and metalloids in medicines used to treat iron deficiency anemia, using chromatographic and non-chromatographic techniques. In the first part of this thesis, lead was determined in drugs using electrothermal atomic absorption spectrometry (ETAAS). Sample preparation was performed using acid digestion in digester block with reflux system "cold finger" using 3 mL of HNO3 (69% v / v) and 1 mL of H2O2 (30% v / v). Pyrolysis and atomization temperatures were optimized using a mixture of palladium and magnesium as conventional chemical modifier, yielding 1100°C and 2000°C for pyrolysis and atomization, respectively. With a characteristic mass of 21.3 pg and 0.25 and 0.82 µg g-1, for limit of detection (LOD) and limit of quantification (LOQ), respectively. The accuracy, expressed as relative standard deviation was 5.92% for a sample with lead concentration of 2.98 µg g-1. The accuracy was evaluated by comparing the results obtained by ETAAS and inductively coupled plasma mass spectrometry (ICP-MS). Lead concentrations found in samples ranged between 0.096 and 7.068 µg g-1. In the second part of this work, the determination of mercury using slurry sampling and high resolution continuous source cold vapor atomic absorption spectroscopy (HR-CS CVAAS) was performed. The optimum conditions for preparation of slurries (1.5 mol L-1 HCl, 1.25% (w / v) thiourea and 15 minutes sonication) were optimized using a two level full factorial design. The limits of detection and quantification were 0.63 ng g-1 and 2.11 ng g-1, respectively. The relative standard deviation for accuracy evaluation was calculated using two samples with concentrations 4.82 and 9.61 ng g-1 from which was obtained as results 10.89 and 6.84%, respectively. The possible loss of mercury was evaluated for the proposed procedure and the accuracy was studied by addition/recovery test, with recoveries ranging from 85.0 to 106.0%. Mercury concentrations ranged between 3.17 and 34.86 ng g-1. The third part of this work describes the determination of macro and micro elements and the in vitro study of iron bioaccessibility in medicines used to treat iron deficiency anemia. It was used inductively coupled plasma optical emission spectrometry (ICP OES) measured as an analytical technique. Acid digestion treatment was conducted to the samples and the method was fully validated by demonstrating good sensitivity with quantification limits (mg L-1) 0.52 for Ca, 0.14 for K, 0.03 for Mg, 0.07 for Mn, 0.40 for Na, 0.36 for P and 0.24 for Zn. The precision of the method was evaluated by intraday and interday repetitive experiments with results below 20%. During accuracy evaluation, addition/recovery tests were performed at different concentrations with results between 81.85 and 114.97%. The robustness of plasma was evaluated by a ratio between magnesium atomic and ionic lines, Mg(II)/Mg(I). The results were evaluated by multivariate analysis tools, principal component analysis (PCA) and hierarchical cluster analysis (HCA). The study of in vitro bioaccessibility of Fe showed that some drugs are better bioaccessible, being therefore more recommended for anemia treatment, confirming data of pharmacological literature. The fourth part of this work describes the simultaneous determination of arsenic and chromium speciation using high-performance liquid chromatography coupled to ICP-MS (HPLC-ICP- MS). The total arsenic and chromium determination was carried out using an acid digestion in microwave oven, using a mixture of 4 mL HNO3 (69% v / v) 9 and 1 mL of H2O2 (30% v / v) and analyzed by ICP-MS. For speciation, a study was performed with three possible procedures for extraction of species, being employed a procedure with water at 80 °C for 30 minutes in microwave energy. Using a mobile phase containing 1.0 mM tetrabutylammonium hydroxide (TBAH), 0.7 mM ethylenediaminetetraacetic acid (EDTA) and 5% methanol (v / v) under pH 7.2 was possible the separation of the species present with retention time of 5 minutes with separation of As(III) As(V), Cr(III) and Cr(VI), with a LOD of 0.002, 0.003, 0.140 and 0.042 µg g-1, respectively. The accuracy was assessed using addition/recovery tests, ranging between 80.64 and 109.36%. The method was applied in samples from Brazil and Spain.

Ce travail de thèse, effectué dans le cadre du projet européen MClocks (http://www.inrim.it/mclocks), reporte le développement et la caractérisation métrologique d’une horloge atomique à cellule de césium de haute performance basée sur le phénomène de piégeage cohérent de population (CPT). Cette horloge exploite un schéma de pompage CPT optimisé nommé push-pull optical pumping (PPOP), permettant la détection de résonances CPT à fort contraste sur la transition d’horloge 0-0. Une caractérisation détaillée des différents éléments de l’horloge est reportée. L’horloge fut exploitée en mode continu (CW) et en mode impulsionnel de type Ramsey. Dans les deux modes de fonctionnement, l’horloge démontre une stabilité relative de fréquence de l’ordre de 2 10−13 τ−1/2 jusque 100 s d’intégration, principalement limitée par des effets de puissance laser. Cette horloge atomique, parmi les meilleures horloges à cellule développées à travers le monde, pourrait trouver des applications pour les systèmes de télécommunications, d’instrumentation, de défense ou navigation par satellite.Cette thèse reporte aussi une technique originale de stabilisation de fréquence laser par spectroscopie sub-Dopplerbi-fréquence en cellule. La plateforme constituée par l’horloge a été utilisée pour mener des tests de physique plus amont incluant la caractérisation par spectroscopie CPT d’une cellule de césium avec un revêtement anti-relaxant OTS (octadecyltrichlorosilane) ou la caractérisation de microcellules à vapeur de césium avec gaz tampon développées à FEMTO-ST pour des horloges atomiques miniatures. / This thesis work, performed in the frame of the MClocks European project (http://www.inrim.it/mclocks), reports the development and metrological characterization of a high-performance Cs vapor cell atomic clock based on coherent population trapping (CPT). The clock uses an optimized CPT pumping scheme, named push-pull optical pumping (PPOP), allowing the detection of high-contrast CPT resonances on the 0-0 magnetic-field insensitive clock transition. A detailed characterization of key components of the clock is reported. The clock was operated in the continuous-wave (CW) regime and in a Ramsey-like pulsed regime. In both regimes, the clock demonstrates a short-term fractional frequency stability at the level of 2 10−13 τ−1/2 up to 100 s averaging time, mainly limited by laser power effects. This CPT clock, ranking among the best microwave vapor cell atomic frequency standards, could find applications in telecommunication, instrumentation, defense or satellite-based navigation systems.This thesis reports also a novel laser frequency stabilization technique using dual-frequency sub-Doppler spectroscopy in a vapor cell. The clock ”platform” has also been used to perform using CPT spectroscopy the characterization of a Cs vapor cell coated with octadecyltrichlorosilane (OTS) or original buffer-gas filled Cs vapor micro-fabricated cells developed in FEMTO-ST for CPT-based miniature atomic clocks.

The thesis is focused on radiological and chemical weapons in the context of their use in terrorist attacks against the civilian population in relation to rescue and clean up operations of the Integrated Rescue System (IRS) of the Czech Republic. The objective of the thesis is to specify the terms of radiological and chemical weapons, to assess potential negative consequences of their use with the emphasis on the threat to life and health of the population, to evaluate the economic impact on society and to compare the IRS activities during the immediate intervention carried out after a terrorist attack. The topic is dealt with based on the research and the analysis of rules of law in force regulating activities of the IRS components in these major incidents and also of documents of the IAEA (International Atomic Energy Agency) and other works focused on the misuse of radioactive and chemical agents in terrorist attacks. Severity and complexity of the issue is illustrated by information given on the radiological accident in Goiana in Brazil, sarin attacks of the Japanese sect Óm šinrikjó and consequences of the model example of the use of radionuclide 137Cs. In the thesis the current methodology on which the IRS components operate in such emergencies is analyzed, and some aspects that are subject of the set of type activities, worked out by the Civil Emergency Planning Committee and DG Fire Rescue Service of the CR, which may become weak points during a real action of the IRS, are pointed out. One of major issues analyzed in this study is comparison of radiological and chemical attacks with the focus on the initial phase of the intervention of the IRS components. Presentation of differences in individual activities of the IRS components in such interventions can contribute significantly to understanding and subsequently managing the activities carried out by the IRS components in these major incidents.