Les travaux présentés dans cette thèse de doctorat portent sur létude de la distribution cellulaire dynamique des facteurs essentiels dépissage de la famille SR dArabidopsis thaliana. Le processus dexcision/épissage du pré-mRNA consiste en la reconnaissance précise des introns au niveau des sites dépissage, en leur excision et en la ligature des exons. Les facteurs d'épissage SR possèdent un domaine particulier riche en dipeptides sérines et arginines répétés et également un ou deux domaines hautement conservés de liaison au RNA. Ils sont impliqués dans la reconnaissance et le choix des sites dépissage ainsi que dans lassemblage du spliceosome. Au cours de cette thèse de doctorat, nous avons montré la distribution subcellulaire dynamique des protéines SR d'Arabidopsis (RSp31, RSZp22, RSp34 et RSZ33) fusionnée à la GFP, et ce dans divers systèmes expérimentaux (cellules foliaires de tabac et dArabidopsis, cellules BY-2). Celles-ci se localisent au sein du noyau et se concentrent en certains sites nucléaires précis dénommés speckles. Nous avons aussi observé que lune dentre-elles, RSZp22, peut se localiser au sein du nucléole suivant les conditions cellulaires, ce qui suggérait un rôle possible de cette protéine dans le transport du mRNA. Nous avons étudié le rôle des différents domaines structuraux des protéines SR dans leur distribution cellulaire en réalisant des délétions partielles des protéines RSp31 et RSZp22 et en analysant la localisation des protéines mutantes. Par co-expression de différents couples de protéines SR fusionnées à deux variantes de protéines fluorescentes (la GFP et la mRFP1 ou monomeric Red Fluorescent Protein 1), nous avons également montré une co-localisation générale des protéines SR végétales, à lexception de RSZp22 qui est la seule à présenter cette localisation nucléolaire. Nous avons aussi analysé la redistribution des protéines SR après traitement par divers inhibiteurs de la phosphorylation et déphosphorylation et également de la transcription. Aussi, l'utilisation de diverses méthodes de microscopie confocale (comme le FRAP ou Fluorescence Recovery After Photobleaching ou encore le FLIP ou Fluorescence Loss In Photobleaching) nous a permis de montrer que les protéines SR dArabidopsis sont hautement dynamiques au sein du noyau. Enfin, nous avons observé grâce à la technique du FLIP que RSZp22 est capable de faire la navette entre le noyau et le cytoplasme et que ce transport nucléo-cytoplasmique dépend de la voie dexportation via le récepteur CRM1/exportine1 [1-3]. 1. Docquier, S., et al., Nuclear bodies and compartmentalization of pre-mRNA splicing factors in higher plants. Chromosoma, 2004. 112(5): p. 255-66. 2. Tillemans, V., et al., Functional distribution and dynamics of Arabidopsis SR splicing factors in living plant cells. Plant J, 2005. 41(4): p. 567-82. 3. Tillemans, V., et al., Insights into Nuclear Organization in Plants as Revealed by the Dynamic Distribution of Arabidopsis SR Splicing Factors. Plant Cell, 2006. 18(11): p. 3218-34.

Dans les cellules eucaryotes, lexport des ARN messagers du noyau vers le cytoplasme est un processus complexe et régulé. Les messagers matures sont transportés par le récepteur dexport TAP/NXF1, qui est recruté au niveau des messagers par différents adaptateurs comme les protéines Aly/REF, UAP56 et les protéines SR. Dans le cadre dune infection virale, en plus des messagers cellulaires, de nombreux messagers viraux doivent être transportés efficacement dans le cytoplasme pour y être traduits. Il est maintenant établi que les herpesvirus codent pour une famille conservée de gènes dont les produits agissent en tant que facteurs dexport et régulent le transport des transcrits viraux. Cette famille inclut la protéine IE4 du virus de la Varicelle et du Zona (VZV). Les principales caractéristiques de ces facteurs dexport viraux sont leur capacité à faire la navette entre le noyau et le cytoplasme, leur domaine de liaison à lARN, et leur capacité à interagir avec des facteurs intervenant dans lexport des messagers cellulaires. Avant cette étude, les données montraient que la protéine IE4 agit comme un régulateur important de lexpression des gènes viraux et cellulaires, mais les mécanismes impliqués nétaient pas clairement définis. Dans ce travail, nous avons identifié de nouveaux partenaires cellulaires de la protéine IE4, et, bien que des différences existent, nous avons montré que la protéine IE4 partage les caractéristiques des facteurs dexport viraux. Nous avons montré que la protéine IE4 interagit avec trois protéines SR, à savoir ASF/SF2, 9G8 et SRp20. Nous avons identifié le domaine dinteraction au sein de la protéine IE4 et montré que ces interactions ne sont pas dépendantes de la présence dARN. Nous avons démontré que la protéine IE4 interagit avec la principale kinase phosphorylant les protéines SR, SRPK1, et quelle est phosphorylée par cette kinase. Nous avons montré que la protéine IE4 se lie à lARN, et que la présence dARN stabilise des complexes contenant la protéine IE4 et les facteurs dexport cellulaires TAP/NXF1 et Aly/REF. Enfin, nous avons déterminé linfluence de la protéine IE4 sur lexport de messagers rapporteurs, et clairement montré que linfection par le VZV utilise le facteur dexport TAP/NXF1 pour exporter certains transcrits viraux. Nous avons donc mis en évidence un nouvel exemple de facteur dexport viral et proposé en modèle dexport des messagers viraux régulé par la protéine IE4. Nos résultats démontrent clairement que les herpesvirus ont développé différents mécanismes pour réguler lexport des ARN dans le but daltérer lexpression des gènes cellulaires au profit de lexpression des gènes viraux.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A área estudada está inserida na Faixa Ribeira, Segmento Central da Província Mantiqueira (Almeida et al., 1973, 1977, 1981), que representa um cinturão de dobramentos e empurrões gerado no Neo-proterozóico/Cambriano, durante a Orogênese Brasiliana, na borda sul/sudeste do Cráton do São Francisco (Almeida, 1971, 1977; Cordani et al., 1967, 1973; Cordani & Brito Neves, 1982; Teixeira & Figueiredo, 1991). Neste contexto, o Complexo Quirino é o embasamento retrabalhado do Terreno Paraíba do Sul (Heilbron et al., 2004). O Complexo Quirino é formado por extensos corpos de ortognaisses foliados a homogêneos, leuco a mesocráticos, de granulometria média à grossa, composicionalmente variando entre granitóides tonalíticos/granodioríticos a graníticos, e apresentando enclaves de rochas ultramáficas, máficas e cálcio-silicáticas (ricas em tremolita). Os ortognaisses tonalíticos/granodioríticos apresentam porfiroblastos de plagioclásio e a hornblenda como máfico principal, contrastando com os de composição granítica que apresentam porfiroblastos de K-feldspato e biotita predominante. Como acessórios aparecem zircão, titanita, apatita e epidoto. Também estão associados a estes ortognaisses, granitóides neoproterozóicos que formam corpos individualizados ou lentes anatéticas no conjunto paleoproterozóico. Estes são compostos predominantemente por biotita gnaisse e hornblenda-biotita gnaisse. A análise litogeoquímicas dos ortognaisses do Complexo Quirino demonstrou a existência de duas séries magmáticas distintas. A primeira pertencente à série cálcio-alcalina de alto-K apresenta uma composição mais expandida granítica-adamelítica/granodioritica/tonalítica e é correlacionável aos bt-ortognaisses e alguns hb-bt-ortognaisses. Os ortognaisses da série médio-K apresentam composição predominantemente tonalítica, sendo correlacionáveis à maioria dos hornblenda-biotita gnaisses. Enclaves lenticulares de metapiroxeníticos e anfibolíticos ocorrem em muitos afloramentos. Também ocorrem granitóides neoproterozóicos de composição graníticas a quartzo-monzoníticas O estudo isotópico de Sm-Nd e Sr demonstrou que os ortognaisses da série cálcio-alcalina de alto-K e aqueles da série cálcio-alcalina de médio-K possuem idades modelo TDM variando entre paleoproterozóicas a arqueanas, consistentes com dados U-Pb em zircão publicados na literatura. A série cálcio-alcalina de alto-K é mais antiga (2308 9,2 Ma a 2185 8 Ma) do que a série calcio-alcalina de médio-K (2169 3 a 2136 14 Ma) e a existência de zircões herdados com idades mínimas de 2846 Ma e 2981 Ma para série de médio-K e 3388 16 para série de alto-K. Os granitóides brasilianos possuem idades de cristalização neoproterozóica correlacionada a Orogênese Brasiliana (602 a 627 Ma) (Viana, 2008; Valladares et al., 2002)./Com base nos dados de Sr e Sm-Nd foi possível caracterizar 4 grupos distintos. Os grupos 1 e 2 são formados por rochas de idade paleoproterozóica (2,1 a 2,3 Ga) com idades modelo TDM variando de 2,9 e 3,4 Ga, εNd entre -8,1 e -5,8 e 87Sr/86Sr(t) = 0,694707 (Grupo 1) e TDM variando de 2,5 a 2,7 Ga, εNd entre -5,8 e -3,1 e 87Sr/86Sr(t) = 0,680824 (Grupo 2), formados no paleoproterozóico com contribuição de uma crosta arqueana. O grupo 3 é formado por rochas juvenis de idade paleoproterozóica, com idades de cristalização variando entre 2,0 e 2,2 Ga e com idades modelo TDM variando de 2,1 a 2,2 Ga e εNd entre + 1,5 e + 1,2. O grupo 4 é formado durante o neoproterozóico (645 Ma) por rochas possivelmente de idade paleoproterozóico com idades modelo TDM igual a 1,7 Ga e εNd igual a -8,3. / The study area is part of the Ribeira Belt, Central Segment Mantiqueira Province (Almeida et al., 1973, 1977, 1981), which represents one of fold-thrust belt in neoproterozoic/cambrian generated during the Brasiliano Orogeny, at the edge south / southeast of the São Francisco Craton (Almeida, 1971, 1977, Cordani et al., 1967, 1973, Brito Neves & Cordani, 1982, Teixeira and Figueiredo, 1991). In this context, the Quirino Complex is the reworked basement of Paraiba do Sul Terrain (Heilbron et al., 2004). Quirino Complex is formed by extensive bodies of foliated orthogneisses the homogeneous, the leuco mesocratic, average particle size of the thick, compositionally ranging from tonalitic granitoids / granodioritic to granitic, and featuring enclaves of ultramafic, mafic and calcium silicate (rich in tremolite). The tonalite orthogneiss / granodioritic present porphyroblasts of plagioclase and hornblende as mafic main, contrasting with those of granitic composition showing porphyroblasts of K-feldspar and biotite predominates. Accessories appear as zircon, titanite, apatite and epidote. Also associated with these orthogneisses, neoproterozoic granitoids that make up individual bodies or lenses in the set anatetics paleoproterozoic. These are composed predominantly of biotite gneiss and hornblende-biotite gneiss. Lithogeochemical analysis of orthogneiss from Quirino Complex suggest the existence of two distinct magmatic series. The first belongs to the high-K calc-alkaline series composition shows a more expanded granitic-adamelític/granodioritic/tonalitic and is correlated to some orthogneisses and bt-hb-bt-orthogneiss. The medium-K orthogneisses series feature predominantly tonalitic composition, and correlated to most of the hornblende-biotite gneiss. Lenses enclaves metapiroxenitics and amphibolites occur in many outcrops. Neoproterozoic granitoids also occur composition of granitic to quartz-monzonitic. The isotopic study of Sm-Nd and Sr showed that the high-K calc-alkaline series orthogneisses and those of medium-K calc-alkaline series, have TDM model ages ranging from Archean to Paleoproterozoic, consistent with U-Pb data zircon from the literature. The high-K calc-alkaline series is older (2308 9.2 Ma to 2185 8 Ma) than medium-K calc-alkaline series (2169 3 to 2136 14 Ma) and occurs the existence of zircons inherited with minimum ages of 2846 Ma and 2981 Ma for medium-K series and 3388 16 for high-K series. The brasiliano granitoids have neoproterozoic crystallization ages correlated to Brasiliano Orogeny (602-627 Ma) (Viana, 2008, Valladares et al., 2002). Based on data of Sr and Sm-Nd was possible to identify four distinct groups. Groups 1 and 2 are formed by rocks of Paleoproterozoic (2.1 to 2.3 Ga) TDM model ages ranging from 2.9 to 3.4 Ga, εNd between -8.1 and -5.8 and 87Sr / 86Sr ratios (t) = 0.694707 (Group 1) and TDM ranging from 2.5 to 2.7 Ga, εNd between -5.8 and -3.1 and 87Sr/86Sr (t) = 0.680824 (Group 2), formed with the assistance of a Paleoproterozoic Archean. The third group consists of Paleoproterozoic juvenile rocks with crystallization ages ranging between 2.0 and 2.2 Ga and TDM model ages ranging from + 2.1 to + 2.2 Ga and εNd between +1.5 and +1.2. Group 4 is formed during the Neoproterozoic (645 Ma) of rocks with Paleoproterozoic age possibly TDM model ages exceeding 1.7 Ga and εNd= -8.3.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A área estudada está inserida na Faixa Ribeira, Segmento Central da Província Mantiqueira (Almeida et al., 1973, 1977, 1981), que representa um cinturão de dobramentos e empurrões gerado no Neo-proterozóico/Cambriano, durante a Orogênese Brasiliana, na borda sul/sudeste do Cráton do São Francisco (Almeida, 1971, 1977; Cordani et al., 1967, 1973; Cordani & Brito Neves, 1982; Teixeira & Figueiredo, 1991). Neste contexto, o Complexo Quirino é o embasamento retrabalhado do Terreno Paraíba do Sul (Heilbron et al., 2004). O Complexo Quirino é formado por extensos corpos de ortognaisses foliados a homogêneos, leuco a mesocráticos, de granulometria média à grossa, composicionalmente variando entre granitóides tonalíticos/granodioríticos a graníticos, e apresentando enclaves de rochas ultramáficas, máficas e cálcio-silicáticas (ricas em tremolita). Os ortognaisses tonalíticos/granodioríticos apresentam porfiroblastos de plagioclásio e a hornblenda como máfico principal, contrastando com os de composição granítica que apresentam porfiroblastos de K-feldspato e biotita predominante. Como acessórios aparecem zircão, titanita, apatita e epidoto. Também estão associados a estes ortognaisses, granitóides neoproterozóicos que formam corpos individualizados ou lentes anatéticas no conjunto paleoproterozóico. Estes são compostos predominantemente por biotita gnaisse e hornblenda-biotita gnaisse. A análise litogeoquímicas dos ortognaisses do Complexo Quirino demonstrou a existência de duas séries magmáticas distintas. A primeira pertencente à série cálcio-alcalina de alto-K apresenta uma composição mais expandida granítica-adamelítica/granodioritica/tonalítica e é correlacionável aos bt-ortognaisses e alguns hb-bt-ortognaisses. Os ortognaisses da série médio-K apresentam composição predominantemente tonalítica, sendo correlacionáveis à maioria dos hornblenda-biotita gnaisses. Enclaves lenticulares de metapiroxeníticos e anfibolíticos ocorrem em muitos afloramentos. Também ocorrem granitóides neoproterozóicos de composição graníticas a quartzo-monzoníticas O estudo isotópico de Sm-Nd e Sr demonstrou que os ortognaisses da série cálcio-alcalina de alto-K e aqueles da série cálcio-alcalina de médio-K possuem idades modelo TDM variando entre paleoproterozóicas a arqueanas, consistentes com dados U-Pb em zircão publicados na literatura. A série cálcio-alcalina de alto-K é mais antiga (2308 9,2 Ma a 2185 8 Ma) do que a série calcio-alcalina de médio-K (2169 3 a 2136 14 Ma) e a existência de zircões herdados com idades mínimas de 2846 Ma e 2981 Ma para série de médio-K e 3388 16 para série de alto-K. Os granitóides brasilianos possuem idades de cristalização neoproterozóica correlacionada a Orogênese Brasiliana (602 a 627 Ma) (Viana, 2008; Valladares et al., 2002)./Com base nos dados de Sr e Sm-Nd foi possível caracterizar 4 grupos distintos. Os grupos 1 e 2 são formados por rochas de idade paleoproterozóica (2,1 a 2,3 Ga) com idades modelo TDM variando de 2,9 e 3,4 Ga, εNd entre -8,1 e -5,8 e 87Sr/86Sr(t) = 0,694707 (Grupo 1) e TDM variando de 2,5 a 2,7 Ga, εNd entre -5,8 e -3,1 e 87Sr/86Sr(t) = 0,680824 (Grupo 2), formados no paleoproterozóico com contribuição de uma crosta arqueana. O grupo 3 é formado por rochas juvenis de idade paleoproterozóica, com idades de cristalização variando entre 2,0 e 2,2 Ga e com idades modelo TDM variando de 2,1 a 2,2 Ga e εNd entre + 1,5 e + 1,2. O grupo 4 é formado durante o neoproterozóico (645 Ma) por rochas possivelmente de idade paleoproterozóico com idades modelo TDM igual a 1,7 Ga e εNd igual a -8,3. / The study area is part of the Ribeira Belt, Central Segment Mantiqueira Province (Almeida et al., 1973, 1977, 1981), which represents one of fold-thrust belt in neoproterozoic/cambrian generated during the Brasiliano Orogeny, at the edge south / southeast of the São Francisco Craton (Almeida, 1971, 1977, Cordani et al., 1967, 1973, Brito Neves & Cordani, 1982, Teixeira and Figueiredo, 1991). In this context, the Quirino Complex is the reworked basement of Paraiba do Sul Terrain (Heilbron et al., 2004). Quirino Complex is formed by extensive bodies of foliated orthogneisses the homogeneous, the leuco mesocratic, average particle size of the thick, compositionally ranging from tonalitic granitoids / granodioritic to granitic, and featuring enclaves of ultramafic, mafic and calcium silicate (rich in tremolite). The tonalite orthogneiss / granodioritic present porphyroblasts of plagioclase and hornblende as mafic main, contrasting with those of granitic composition showing porphyroblasts of K-feldspar and biotite predominates. Accessories appear as zircon, titanite, apatite and epidote. Also associated with these orthogneisses, neoproterozoic granitoids that make up individual bodies or lenses in the set anatetics paleoproterozoic. These are composed predominantly of biotite gneiss and hornblende-biotite gneiss. Lithogeochemical analysis of orthogneiss from Quirino Complex suggest the existence of two distinct magmatic series. The first belongs to the high-K calc-alkaline series composition shows a more expanded granitic-adamelític/granodioritic/tonalitic and is correlated to some orthogneisses and bt-hb-bt-orthogneiss. The medium-K orthogneisses series feature predominantly tonalitic composition, and correlated to most of the hornblende-biotite gneiss. Lenses enclaves metapiroxenitics and amphibolites occur in many outcrops. Neoproterozoic granitoids also occur composition of granitic to quartz-monzonitic. The isotopic study of Sm-Nd and Sr showed that the high-K calc-alkaline series orthogneisses and those of medium-K calc-alkaline series, have TDM model ages ranging from Archean to Paleoproterozoic, consistent with U-Pb data zircon from the literature. The high-K calc-alkaline series is older (2308 9.2 Ma to 2185 8 Ma) than medium-K calc-alkaline series (2169 3 to 2136 14 Ma) and occurs the existence of zircons inherited with minimum ages of 2846 Ma and 2981 Ma for medium-K series and 3388 16 for high-K series. The brasiliano granitoids have neoproterozoic crystallization ages correlated to Brasiliano Orogeny (602-627 Ma) (Viana, 2008, Valladares et al., 2002). Based on data of Sr and Sm-Nd was possible to identify four distinct groups. Groups 1 and 2 are formed by rocks of Paleoproterozoic (2.1 to 2.3 Ga) TDM model ages ranging from 2.9 to 3.4 Ga, εNd between -8.1 and -5.8 and 87Sr / 86Sr ratios (t) = 0.694707 (Group 1) and TDM ranging from 2.5 to 2.7 Ga, εNd between -5.8 and -3.1 and 87Sr/86Sr (t) = 0.680824 (Group 2), formed with the assistance of a Paleoproterozoic Archean. The third group consists of Paleoproterozoic juvenile rocks with crystallization ages ranging between 2.0 and 2.2 Ga and TDM model ages ranging from + 2.1 to + 2.2 Ga and εNd between +1.5 and +1.2. Group 4 is formed during the Neoproterozoic (645 Ma) of rocks with Paleoproterozoic age possibly TDM model ages exceeding 1.7 Ga and εNd= -8.3.

This diploma thesis is occupied with analysis of the keys to the maps of Landscape Atlas of the Czech Republic and the Landscape Atlas of the Slovak Republic with emphasis on their mutual comparison. This thesis based on the published general theoretical principles of cartographic production. The theoretical part concludes with a chapter that engages in the key in detail, its types, procedures, etc. Then come critical analysis and classification keys to the maps of Landscape Atlas of the CR and subsequent comparison with Landscape Atlas of the SR using objective cartographic criteria. There is observed mainly the overall clarity, completeness, graphical representation and last but not least the overall look of the keys.

No description available.

In signal processing field, there are various measures that can be employed to analyse and represent the signal in order to obtain meaningful outcome. Sparse representation (SR) has continued to receive great attention as one of the well-known tools in statistical theory which among others, is used to extract specific latent temporal features that can reveal salient primitive and sparsely represented features of complex data signals, including temporal data analysis. Under reasonable conditions, many signals are assumed to be sparse within a domain, such as spatial, time, or timefrequency domain, and this sparse characteristics of such signals can be obtained through the SR. The ECG signal, for instance, is typically a temporal sparse signal, comprises of various periodic activities such as time delay and frequency amplitudes, plus additive noise and possible interference. Particularly challenging in signal processing, especially time series signals is how to reconstruct and extract the various features that characterized the signal. Many problems (e.g., signal components analysis, feature extraction/selection in signals, signal reconstruction, and classification) can be formulated as linear models and solved using the SR technique The reconstruction of signals through SR can offer a rich representation of the sparsified temporal structure of the original signal. Due to its numerous advantages, such as noise tolerance and widespread use in various signal processing tasks, this has motivated many researchers to adopt the use of this technique for various signal representation analysis for a better and richer representation of the original input signal. In line with this, therefore, the goal of this study is to propose a SR-based mathematical framework and a coherence function for reconstruction and feature extraction from signals for subsequent analysis. The time embedding principle was first applied to restructure the signal into tine delay vectors and then the proposed approach, referred to as temporal subsequence SR approach was used to reconstruct the noisy signals and provides a sparsified time dependent input signal representation, and then the coherence function is further used to compute and extract the correlational coefficient quantities between the temporal subsequence signals to form the final feature vectors representing the discriminative features for each of the signal. These final feature vectors representing the signal are further used as inputs to machine learning classifiers. Experiments are carried out to illustrate the usefulness of the proposed methods and to assess their impact on the classification performance of the SVM and MLP classifiers using the popular and widely used ECG time series benchmark dataset. This research study supports the general hypothesis that, signal reconstruction methods (datadriven approach) can be valuable in learning compact features from the original signals for classifications.

La mesure de l’émittance transverse du faisceau est fondamentale pour tous les accélérateurs, et en particulier pour les collisionneurs, son évaluation precise étant essentielle pour maximiser la luminosité et ainsi la performance des faisceaux de collision.Le rayonnement synchrotron (SR) est un outil polyvalent pour le diagnostic non-destructif de faisceau, exploité au CERN pour mesurer la taille des faisceaux de protons des deux machines du complexe dont l’énergie est la plus élevée, le SPS et le LHC où l’intensité du faisceau ne permet plus les techniques invasives.Le travail de thèse documenté dans ce rapport s’est concentré sur la conception, le développement, la caractérisation et l’optimisation des moniteurs de taille de faisceau basés sur le SR. Cette étude est fondée sur un ensemble de calculs théoriques, de simulation numériques et d’expériences conduite au sein des laboratoires et accélérateurs du CERN. Un outil de simulation puissant a été développé, combinant des logiciels classiques de simulation de SR et de propagation optique, permettant ainsi la caractérisation complète d’un moniteur SR de la source jusqu’au détecteur.La source SR a pu être entièrement caractérisée par cette technique, puis les résultats validés par observation directe et par la calibration à basse énergie basée sur les mesures effectuées avec les wire-scanners (WS), qui sont la référence en terme de mesure de taille de faisceau, ou telles que la comparaison directe avec la taille des faisceaux obtenue par déconvolution de la luminosité instantanée du LHC.Avec l’augmentation de l’énergie dans le LHC (7TeV), le faisceau verra sa taille diminuer jusqu’à atteindre la limite de la technique d’imagerie du SR. Ainsi, plusieurs solutions ont été investiguées afin d’améliorer la performance du système: la sélection d’une des deux polarisations du SR, la réduction des effets liés à la profondeur de champ par l’utilisation de fentes optiques et l’utilisation d’une longueur d’onde réduite à 250 nm.En parallèle à l’effort de réduction de la diffraction optique, le miroir d’extraction du SR qui s’était avéré être la source principale des aberrations du système a été entièrement reconçu. En effet, la détérioration du miroir a été causée par son couplage EM avec les champs du faisceau, ce qui a conduit à une surchauffe du coating et à sa dégradation. Une nouvelle géométrie de miroir et de son support permettant une douce transition en termes de couplage d’impédance longitudinale dans le beam pipe a été définie et caractérisée par la technique dite du “streched wire”. Egalement, comme méthode alternative à l’imagerie directe, un nouveau moniteur basé sur la technique d’interférométrie à deux fentes du SR, non limité par la diffraction, a également été développé. Le principe de cette méthode est basé sur la relation directe entre la visibilité des franges d’interférence et la taille de faisceau.Comme l’emittance du faisceau est la donnée d’intérêt pour la performance du LHC, il est aussi important de caractériser avec précision l’optique du LHC à la source du SR. Dans ce but, la méthode “K-modulation” a été utilisée pour la première fois au LHC en IR4. Les β ont été mesurés à l’emplacement de tous les quadrupoles et ont été évalués via deux algorithmes de propagation différents au BSRT et au WS. / Measuring the beam transverse emittance is fundamental in every accelerator, in particular for colliders, where its precise determination is essential to maximize the luminosity and thus the performance of the colliding beams.
 Synchrotron Radiation (SR) is a versatile tool for non-destructive beam diagnostics, since its characteristics are closely related to those of the source beam. At CERN, being the only available diagnostics at high beam intensity and energy, SR monitors are exploited as the proton beam size monitor of the two higher energy machines, the Super Proton Synchrotron (SPS) and the Large Hadron Collider (LHC). The thesis work documented in this report focused on the design, development, characterization and optimization of these beam size monitors. Such studies were based on a comprehensive set of theoretical calculations, numerical simulations and experiments.A powerful simulation tool has been developed combining conventional softwares for SR simulation and optics design, thus allowing the description of an SR monitor from its source up to the detector. 
The simulations were confirmed by direct observations, and a detailed performance studies of the operational SR imaging monitor in the LHC, where different techniques for experimentally validating the system were applied, such as cross-calibrations with the wire scanners at low intensity (that are considered as a reference) and direct comparison with beam sizes de-convoluted from the LHC luminosity measurements.In 2015, the beam sizes to be measured with the further increase of the LHC beam energy to 7 TeV will decrease down to ∼190 μm. In these conditions, the SR imaging technique was found at its limits of applicability since the error on the beam size determination is proportional to the ratio of the system resolution and the measured beam size. Therefore, various solutions were probed to improve the system’s performance such as the choice of one light polarization, the reduction of depth of field effect and the reduction of the imaging wavelength down to 250 nm.In parallel to reducing the diffraction contribution to the resolution broadening, the extraction mirror, found as the main sources of aberrations in the system was redesigned. Its failure was caused by the EM coupling with the beam’s fields that led to overheating and deterioration of the coating. A new system’s geometry featuring a smoother transition in the beam pipe was qualified in terms of longitudinal coupling impedance via the stretched wire technique. A comparison with the older system was carried out and resulted in a reduction of the total power dissipated in the extraction system by at least a factor of four.A new, non-diffraction limited, SR-based monitor based on double slit interferometry was designed as well as an alternative method to the direct imaging. Its principle is based on the direct relation between the interferogram fringes visibility and the beam size.Since the beam emittance is the physical quantity of interest in the performance analysis of the LHC, determining the optical functions at the SR monitors is as relevant as measuring the beam size. The “K-modulation” method for the optical function determination was applied for the first time in the LHC IR4, where most of the profile monitors sit. The βs at the quadrupoles were measured and via two different propagation algorithms the βs at the BSRT and the WS were obtained reducing significantly the uncertainty at the monitors location.

La mesure de l’émittance transverse du faisceau est fondamentale pour tous les accélérateurs, et en particulier pour les collisionneurs, son évaluation precise étant essentielle pour maximiser la luminosité et ainsi la performance des faisceaux de collision.Le rayonnement synchrotron (SR) est un outil polyvalent pour le diagnostic non-destructif de faisceau, exploité au CERN pour mesurer la taille des faisceaux de protons des deux machines du complexe dont l’énergie est la plus élevée, le SPS et le LHC où l’intensité du faisceau ne permet plus les techniques invasives.Le travail de thèse documenté dans ce rapport s’est concentré sur la conception, le développement, la caractérisation et l’optimisation des moniteurs de taille de faisceau basés sur le SR. Cette étude est fondée sur un ensemble de calculs théoriques, de simulation numériques et d’expériences conduite au sein des laboratoires et accélérateurs du CERN. Un outil de simulation puissant a été développé, combinant des logiciels classiques de simulation de SR et de propagation optique, permettant ainsi la caractérisation complète d’un moniteur SR de la source jusqu’au détecteur.La source SR a pu être entièrement caractérisée par cette technique, puis les résultats validés par observation directe et par la calibration à basse énergie basée sur les mesures effectuées avec les wire-scanners (WS), qui sont la référence en terme de mesure de taille de faisceau, ou telles que la comparaison directe avec la taille des faisceaux obtenue par déconvolution de la luminosité instantanée du LHC.Avec l’augmentation de l’énergie dans le LHC (7TeV), le faisceau verra sa taille diminuer jusqu’à atteindre la limite de la technique d’imagerie du SR. Ainsi, plusieurs solutions ont été investiguées afin d’améliorer la performance du système: la sélection d’une des deux polarisations du SR, la réduction des effets liés à la profondeur de champ par l’utilisation de fentes optiques et l’utilisation d’une longueur d’onde réduite à 250 nm.En parallèle à l’effort de réduction de la diffraction optique, le miroir d’extraction du SR qui s’était avéré être la source principale des aberrations du système a été entièrement reconçu. En effet, la détérioration du miroir a été causée par son couplage EM avec les champs du faisceau, ce qui a conduit à une surchauffe du coating et à sa dégradation. Une nouvelle géométrie de miroir et de son support permettant une douce transition en termes de couplage d’impédance longitudinale dans le beam pipe a été définie et caractérisée par la technique dite du “streched wire”. Egalement, comme méthode alternative à l’imagerie directe, un nouveau moniteur basé sur la technique d’interférométrie à deux fentes du SR, non limité par la diffraction, a également été développé. Le principe de cette méthode est basé sur la relation directe entre la visibilité des franges d’interférence et la taille de faisceau.Comme l’emittance du faisceau est la donnée d’intérêt pour la performance du LHC, il est aussi important de caractériser avec précision l’optique du LHC à la source du SR. Dans ce but, la méthode “K-modulation” a été utilisée pour la première fois au LHC en IR4. Les β ont été mesurés à l’emplacement de tous les quadrupoles et ont été évalués via deux algorithmes de propagation différents au BSRT et au WS. / Measuring the beam transverse emittance is fundamental in every accelerator, in particular for colliders, where its precise determination is essential to maximize the luminosity and thus the performance of the colliding beams.
 Synchrotron Radiation (SR) is a versatile tool for non-destructive beam diagnostics, since its characteristics are closely related to those of the source beam. At CERN, being the only available diagnostics at high beam intensity and energy, SR monitors are exploited as the proton beam size monitor of the two higher energy machines, the Super Proton Synchrotron (SPS) and the Large Hadron Collider (LHC). The thesis work documented in this report focused on the design, development, characterization and optimization of these beam size monitors. Such studies were based on a comprehensive set of theoretical calculations, numerical simulations and experiments.A powerful simulation tool has been developed combining conventional softwares for SR simulation and optics design, thus allowing the description of an SR monitor from its source up to the detector. 
The simulations were confirmed by direct observations, and a detailed performance studies of the operational SR imaging monitor in the LHC, where different techniques for experimentally validating the system were applied, such as cross-calibrations with the wire scanners at low intensity (that are considered as a reference) and direct comparison with beam sizes de-convoluted from the LHC luminosity measurements.In 2015, the beam sizes to be measured with the further increase of the LHC beam energy to 7 TeV will decrease down to ∼190 μm. In these conditions, the SR imaging technique was found at its limits of applicability since the error on the beam size determination is proportional to the ratio of the system resolution and the measured beam size. Therefore, various solutions were probed to improve the system’s performance such as the choice of one light polarization, the reduction of depth of field effect and the reduction of the imaging wavelength down to 250 nm.In parallel to reducing the diffraction contribution to the resolution broadening, the extraction mirror, found as the main sources of aberrations in the system was redesigned. Its failure was caused by the EM coupling with the beam’s fields that led to overheating and deterioration of the coating. A new system’s geometry featuring a smoother transition in the beam pipe was qualified in terms of longitudinal coupling impedance via the stretched wire technique. A comparison with the older system was carried out and resulted in a reduction of the total power dissipated in the extraction system by at least a factor of four.A new, non-diffraction limited, SR-based monitor based on double slit interferometry was designed as well as an alternative method to the direct imaging. Its principle is based on the direct relation between the interferogram fringes visibility and the beam size.Since the beam emittance is the physical quantity of interest in the performance analysis of the LHC, determining the optical functions at the SR monitors is as relevant as measuring the beam size. The “K-modulation” method for the optical function determination was applied for the first time in the LHC IR4, where most of the profile monitors sit. The βs at the quadrupoles were measured and via two different propagation algorithms the βs at the BSRT and the WS were obtained reducing significantly the uncertainty at the monitors location.

Controlled release formulations deliver an active ingredient over an extended period of time. It is an ideal dosage form for an active ingredient with a short elimination half-life. An active ingredient with a short elimination half-life would be released in small portions over an extended period of time and thus less frequent administration is necessary and this improve patient compliance. Other advantages of these formulations include: decreased side effects, constant drug levels in the blood, improvement in treatment efficiency and reduction in cost of administration. Controlled release beads are formulated in such a way that the active ingredient is embedded in a matrix of insoluble substance like chitosan; the dissolving drug then has to find its way through the pores of the matrix into the surrounding medium. The chitosan matrix swells to form a gel, the drug then has to first dissolve in the matrix and diffuse through the outer surface into the surrounding medium. Chitosan is a biocompatible, biodegradable polymer of natural origin. It has mucoadhesive properties as well as the ability to manipulate the tight junctions in the epithelium membrane and these properties have qualified chitosan as an effective drug carrier in controlled release dosage forms. The effect of a modern controlled release polymer namely Kollidon® SR in combination with chitosan on drug release was investigated. Ketoprofen was chosen as model drug. Ketoprofen is an anti-inflammatory drug that causes gastrointestinal side effects in conventional dosage forms. Ketoprofen has a short elimination half-life of 2.05 ± 0.58 h and this characteristic makes it an ideal candidate for use in a controlled release formulation. The aim of this study was to achieve controlled release and minimize gastrointestinal effects of ketoprofen with chitosan particles. Kollidon® SR was used as polymer because it exhibits pH independent release characteristics and previous studies have shown potential for this combination. Chitosan beads and chitosan-Kollidon® SR beads, as well as chitosan granules and chitosan-Kollidon® SR granules, were prepared and investigated as potential controlled release formulations. Chitosan beads were prepared through the inotropic gelation method using tripolyphosphate as a cross linking agent. Granules were prepared through wet granulation using 2% v/v acetic acid as the granulating fluid or by dissolving ketoprofen in ethanol and Kollidon® SR in 2-pyrrolidinone and using the solution as granulating fluid. Kollidon® SR was added in concentrations of 0.25, 0.5 and 1% (w/v) in the bead formulations and concentrations of 1, 5 and 10% (w/w) in the granule formulations. The beads and granules were characterised by evaluating the following properties: morphology, drug loading and drug release. Additionally swelling and friability tests were also conducted on the bead formulations. The cross linking times of the bead formulations were varied to investigate the effect of cross linking time on the characteristics of the beads. Chitosan-Kollidon® SR beads showed promising results for controlled release formulations and ketoprofen were released over an extended period of time. Drug loading of the plain chitosan beads was 74.65 ± 0.71% and it was noted that the inclusion of Kollidon® SR in the beads resulted in an increase in drug loading and the formulation containing 1% (w/v) Kollidon® SR, cross linked for 30 minutes had a drug loading of 77.38 ± 0.01%. Drug loading of the beads that were cross linked for a longer time were slightly lower which is an indication that some of the drug might have leached out during cross linking. The degree of swelling was promising with some beads swelling to a degree of 2.5 in phosphate buffer solution pH 5.6. Granules had a drug loading between 81.73 ± 1.53% and 93.30 ± 0.50%. Ketoprofen release from the beads and the granules in PBS pH 7.40 at 37 °C over a period of 6 hours were investigated. The bead formulations were more effective in achieving controlled release and it was noted that the bead formulations that was cross linked for a longer period was more efficient in achieving controlled release. The granules did not form a matrix and were not effective in achieving controlled release. Controlled release of ketoprofen were achieved and the results show potential for chitosan-Kollidon® SR formulations in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.