Nous avons développé une décharge transportée fonctionnant à la pression atmosphérique. Le générateur fonctionne en mode alternative avec une fréquence d’excitation variant entre 1 et 10kHz. Grace à une forme d'onde en dents de scie, il a été possible de transporter la décharge à l’intérieur d’un tube sur une longueur qui pourrait atteindre 200cm. L’influence des différents paramètres tels que la forme de la tension appliquée, le diamètre du tube et la configuration d’électrode, sur la formation de la décharge a été étudié. La nature des espèces excitées à l’intérieur et extérieur du tube a été identifié par Spectroscopie Optique d’Emission. La propagation de la décharge dans un système multi jets et un jet unique de la même section a été comparée. L’influence de ces deux types de jets transportés exposés aux bactéries de type E. coli a été étudiée et les résultats montrent que la zone d’inactivation des bactéries augmente significativement.De plus le potentiel de cette décharge pour le traitement de surface et dépôt des couches minces de polymère a été investigué aussi bien à l’extérieur qu’à l’intérieur du tube capillaire pour la première fois. Nous avons employé deux types de précurseurs: le TEOS, et le DEGME. Sous certaines conditions, les couches de type PEG présentant des propriétés antiadhésives des cellules ont été déposées sur le PS. Afin d’étudier les modifications de surface créées sur les polymères par cette décharge. Les résultats obtenus par des méthodes d’analyse différentes montrent qu’à part l’oxydation de la surface du UHMWPE nous pouvons déceler une insaturation de la surface qui est souvent accompagnée de la réticulation de la surface. / We have developed a transporting discharge source that can operate at atmospheric pressure. The device is working by using AC power supply with a frequency ranging between 1 to 10 kHz. The sawtooth waveform enabled the transport of discharge as long as 200 cm. The different parameters that affect the plasma delivery such as voltage of the waveforms, tube diameter and electrode configuration were investigated. The electronically excited and active species inside and outside of the plasma channel were characterized by Optical Emission Spectroscopy. The electrical and temporal characteristics of the plasma, discharge power and charges on the sample were investigated. The propagation of transporting discharge with multi-jets and a single jet with the same cross-sectional area has been compared. Also, E.coli bacteria were exposed to the transporting discharge multijets and single jet for different time durations.The potential of the transported discharge for the surface treatment of polymers and deposition of thin films has been investigated. Two different precursors namely TEOS, and DEGME have been employed for the elaboration of thin organic coatings by introducing the precursors inside and at the exit of the capillary tube. The PEG like coatings obtained in the case of DEGME on PolyStyrene films showed for particular operating conditions nonadhesive coatings with respect to Ovary Carcinoma Celles. In order to study the surface modification effects of the discharge, the Ultra High Molecular Weight PolyEthylene was used as the substrate in the two different configurations. The results show that besides the oxydation of the UHMWPE, crosslinking takes place.

The hydration and dynamics of the biomolecules appear to be vital for their proper biological functioning. In the presented thesis, various fluorescence techniques were developed and applied to access these properties and their changes upon the mutual interactions of the biomolecules. Initially, the solvent relaxation method based on recording time-dependent fluorescence shift (TDFS) was used to map DNA interactions with proteins and lipids by the newly synthesised fluorene dye covalently bound to the DNA. Secondly, copper-transporting ATPase was probed by Badan attached to the copper-binding cysteine-proline-cysteine motif. The variations in hydration were found to be crucial for the proper ATPase function. Third, a detailed study on quenching of Badan/Prodan fluorescence by tryptophan revealed the limitations of the TDFS method for protein studies, which is essential finding for further applications of TDFS. Fourth application involves investigations of heavy atom effects on the excited state relaxation processes by up-conversion approach in iodinated metallocorroles, which are promising dyes for biological imaging. The obtained findings shall help in further tuning of the optical properties of the corroles desired for the variety of applications. Finally, fluorescence correlation spectroscopy...

A Pipeline Analytical Program and Dredging Knowledge{Base Expert{System (DKBES) determines a pipeline dredge's production and resulting cost and schedule. Pipeline dredge engineering presents a complex and dynamic process necessary to maintain navigable waterways. Dredge engineers use pipeline engineering and slurry transport principles to determine the production rate of a pipeline dredge system. Engineers then use cost engineering factors to determine the expense of the dredge project. Previous work in engineering incorporated an object{oriented expert{system to determine cost and scheduling of mid{rise building construction where data objects represent the fundamental elements of the construction process within the program execution. A previously developed dredge cost estimating spreadsheet program which uses hydraulic engineering and slurry transport principles determines the performance metrics of a dredge pump and pipeline system. This study focuses on combining hydraulic analysis with the functionality of an expert{system to determine the performance metrics of a dredge pump and pipeline system and its resulting schedule. Field data from the U.S. Army Corps of Engineers pipeline dredge, Goetz, and several contract daily dredge reports show how accurately the DKBES can predict pipeline dredge production. Real{time dredge instrumentation data from the Goetz compares the accuracy of the Pipeline Analytical Program to actual dredge operation. Comparison of the Pipeline Analytical Program to pipeline daily dredge reports shows how accurately the Pipeline Analytical Program can predict a dredge project's schedule over several months. Both of these comparisons determine the accuracy and validity of the Pipeline Analytical Program and DKBES as they calculate the performance metrics of the pipeline dredge project. The results of the study determined that the Pipeline Analytical Program compared closely to the Goetz eld data where only pump and pipeline hydraulics a ected the dredge production. Results from the dredge projects determined the Pipeline Analytical Program underestimated actual long{term dredge production. Study results identi ed key similarities and di erences between the DKBES and spreadsheet program in terms of cost and scheduling. The study then draws conclusions based on these ndings and o ers recommendations for further use.

Este trabalho mostra os resultados obtidos durante as atividades de pesquisa e levantamento de dados sobre os equipamentos urbanos de carga denominados Estações Aduaneiras Interiores (EADIs), conhecidos como Portos Secos, na identificação de impactos ambientais resultantes das operações portuárias desses estabelecimentos. O conflito na utilização do espaço viário da área urbana por modos e sistemas de transporte de carga, incumbidos da tarefa de movimentação e transporte de mercadorias dos Portos Secos nas cidades brasileiras, especialmente aquelas de maior porte e em regiões metropolitanas, a saber, caminhões e trens, leva à preocupação tanto pela inexistência de uma legislação específica locacional para estes equipamentos impactantes, como pela grande disseminação destes empreendimentos, especialmente na década de 1990. Aspectos operacionais como a movimentação de cargas e intermodalidade de transportes nas áreas dos Portos Secos, as atividades produtivas urbanas e regionais e a utilização dos Portos Secos, a concentração desses equipamentos nas periferias industriais urbanas das maiores cidades do país, a utilização do sistema viário principal urbano para a viabilização do transporte de cargas, a localização dos Portos Secos e a logística empresarial, entre outros, chamam a atenção num contexto onde o transporte de cargas e o cumprimento das leis geradas pelas políticas governamentais e de regulamentação ainda não reconhecem as necessidades reais das cargas urbanas no Brasil. Aspectos de planejamento para os projetos dos Portos Secos e a atenção à circulação de cargas no ambiente urbano, frente ao uso e ocupação do solo, determinados pelas leis municipais e à infra-estrutura urbana existente, calcados exclusivamente nos custos operacionais e na acessibilidade, subsidiam este trabalho na formulação de diretrizes de planejamento estratégico de uso e ocupação do solo urbano para Portos Secos, para a redução dos impactos ambientais negativos dos transportes urbanos de cargas. Os principais impactos ambientais, que afetam (de forma mais aguda) a área urbana que hospeda o Porto Seco, especialmente nos casos onde não há um estudo de pré-viabilidade e compatibilização do equipamento ao uso e a ocupação do solo, bem como sua adequação às regras do Planejamento Urbano relacionado ao Planejamento dos Transportes tanto nos ambientes físico, natural, político, legal e de planejamento quanto no ambiente sócio-econômico. Examinar o funcionamento de um Porto Seco - EADI Ribeirão Preto - e sua relação impactante na área urbana onde atua, sua movimentação de cargas e prestação de serviços, levando em conta os custos econômicos diretos e indiretos para diferentes atividades, especialmente os custos e impactos ligados aos ambientes natural, social e econômico, faz parte de um diagnóstico a ser elaborado a partir de indicadores de qualidade de funcionamento da área urbana. Os problemas da localização dos Portos Secos induzem a formulação de diretrizes de planejamento estratégico de uso e ocupação do solo que auxiliem na minimização dos impactos ambientais causados durante a realização das tarefas de armazenamento, manuseio, distribuição e transporte de cargas. Os resultados aqui apresentados poderão ser de grande pertinência e utilidade para o poder público na formulação de um quadro legal e de regulamentação e para o segmento empresarial ansioso por melhores decisões estratégicas. Este trabalho apresentará dados, imagens, mapas, tabelas, gráficos, entre outros, tornando-se mais dinâmico na leitura e compreensível no aporte teórico. / The present work brings forth the results of the research and data colleting activities on the freight urban equipment called Interior Custom Stations (ICSs), named EADI in portuguese, also known as Dry Ports, in the identification of the impact the operations carried out in these stations may have on the environment. The problematic use of the urban locomotion spaces by trucks and trains, the modes and systems of freight transportation in charge of moving and transporting freight from the Dry Ports to Brazilian cities, especially the larger and metropolitan ones, in troublesome for the lack of specific local legislation for such impact equipments as well as for their spread in Brazil specially in the 1990th decade. Operational aspects like freight moving and transport intermodality in the Dry Port areas, productive urban and rural activities and the Dry Ports usage, the concentration of these equipments in country\'s larges cities urban industrial outskirts, the location of the Dry Ports and business logistics, among others, call our attention in a context where freight transporting and the fulfillment of the laws created by government and regulation policies still do not understand the real needs of urban freight in Brazil. Planning aspects of the Dry Ports\' Projects together with the attention to the circulation of freight in urban surroundings in face of both use and occupation of the land determined by Municipal laws and the existing urban infra-structure (based exclusively on operational costs and accessibility), support this research in the formulation of strategic planning guidelines of use and occupation of urban land for Dry Ports towards the reduction of negative environmental impacts of urban freight transporting. The major environmental impacts affect (in a more direct way) the urban area that houses the Dry Port, most visibly in cases when there are no studies on the pre-viability and compatibility of the equipment to the use and occupation of the land, as well to its adequacy to the rules of Urban Planning concerning Transport Planning in the physical, natural, political, legal and socio-economical ambience. A close examination of a Dry Port - EADI Ribeirão Preto -, its important relation to the urban area where it is placed, the moving of freight and services offered there taking into account the direct and indirect economic costs for different activities, above all the costs and impacts related to the natural, social and economic ambience, is a part of a diagnosis to be elaborated from the urban functioning quality indicators. The problems in the Dry Ports location lead to the formulation of strategic planning guidelines for the use and occupation of land, which may help minimize environmental impact from storing, handling, distribution and transportation activities. The results brought forth in this work may be of great relevance and usefulness to the government in the formulation of a legal and regulative policy to the business park, longing for better strategic decisions. The present work brings forth data, images, maps, tables, charts, among other kinds of information, which makes its reading more dynamic and understandable in its theoretical discussion.

Este trabalho mostra os resultados obtidos durante as atividades de pesquisa e levantamento de dados sobre os equipamentos urbanos de carga denominados Estações Aduaneiras Interiores (EADIs), conhecidos como Portos Secos, na identificação de impactos ambientais resultantes das operações portuárias desses estabelecimentos. O conflito na utilização do espaço viário da área urbana por modos e sistemas de transporte de carga, incumbidos da tarefa de movimentação e transporte de mercadorias dos Portos Secos nas cidades brasileiras, especialmente aquelas de maior porte e em regiões metropolitanas, a saber, caminhões e trens, leva à preocupação tanto pela inexistência de uma legislação específica locacional para estes equipamentos impactantes, como pela grande disseminação destes empreendimentos, especialmente na década de 1990. Aspectos operacionais como a movimentação de cargas e intermodalidade de transportes nas áreas dos Portos Secos, as atividades produtivas urbanas e regionais e a utilização dos Portos Secos, a concentração desses equipamentos nas periferias industriais urbanas das maiores cidades do país, a utilização do sistema viário principal urbano para a viabilização do transporte de cargas, a localização dos Portos Secos e a logística empresarial, entre outros, chamam a atenção num contexto onde o transporte de cargas e o cumprimento das leis geradas pelas políticas governamentais e de regulamentação ainda não reconhecem as necessidades reais das cargas urbanas no Brasil. Aspectos de planejamento para os projetos dos Portos Secos e a atenção à circulação de cargas no ambiente urbano, frente ao uso e ocupação do solo, determinados pelas leis municipais e à infra-estrutura urbana existente, calcados exclusivamente nos custos operacionais e na acessibilidade, subsidiam este trabalho na formulação de diretrizes de planejamento estratégico de uso e ocupação do solo urbano para Portos Secos, para a redução dos impactos ambientais negativos dos transportes urbanos de cargas. Os principais impactos ambientais, que afetam (de forma mais aguda) a área urbana que hospeda o Porto Seco, especialmente nos casos onde não há um estudo de pré-viabilidade e compatibilização do equipamento ao uso e a ocupação do solo, bem como sua adequação às regras do Planejamento Urbano relacionado ao Planejamento dos Transportes tanto nos ambientes físico, natural, político, legal e de planejamento quanto no ambiente sócio-econômico. Examinar o funcionamento de um Porto Seco - EADI Ribeirão Preto - e sua relação impactante na área urbana onde atua, sua movimentação de cargas e prestação de serviços, levando em conta os custos econômicos diretos e indiretos para diferentes atividades, especialmente os custos e impactos ligados aos ambientes natural, social e econômico, faz parte de um diagnóstico a ser elaborado a partir de indicadores de qualidade de funcionamento da área urbana. Os problemas da localização dos Portos Secos induzem a formulação de diretrizes de planejamento estratégico de uso e ocupação do solo que auxiliem na minimização dos impactos ambientais causados durante a realização das tarefas de armazenamento, manuseio, distribuição e transporte de cargas. Os resultados aqui apresentados poderão ser de grande pertinência e utilidade para o poder público na formulação de um quadro legal e de regulamentação e para o segmento empresarial ansioso por melhores decisões estratégicas. Este trabalho apresentará dados, imagens, mapas, tabelas, gráficos, entre outros, tornando-se mais dinâmico na leitura e compreensível no aporte teórico. / The present work brings forth the results of the research and data colleting activities on the freight urban equipment called Interior Custom Stations (ICSs), named EADI in portuguese, also known as Dry Ports, in the identification of the impact the operations carried out in these stations may have on the environment. The problematic use of the urban locomotion spaces by trucks and trains, the modes and systems of freight transportation in charge of moving and transporting freight from the Dry Ports to Brazilian cities, especially the larger and metropolitan ones, in troublesome for the lack of specific local legislation for such impact equipments as well as for their spread in Brazil specially in the 1990th decade. Operational aspects like freight moving and transport intermodality in the Dry Port areas, productive urban and rural activities and the Dry Ports usage, the concentration of these equipments in country\'s larges cities urban industrial outskirts, the location of the Dry Ports and business logistics, among others, call our attention in a context where freight transporting and the fulfillment of the laws created by government and regulation policies still do not understand the real needs of urban freight in Brazil. Planning aspects of the Dry Ports\' Projects together with the attention to the circulation of freight in urban surroundings in face of both use and occupation of the land determined by Municipal laws and the existing urban infra-structure (based exclusively on operational costs and accessibility), support this research in the formulation of strategic planning guidelines of use and occupation of urban land for Dry Ports towards the reduction of negative environmental impacts of urban freight transporting. The major environmental impacts affect (in a more direct way) the urban area that houses the Dry Port, most visibly in cases when there are no studies on the pre-viability and compatibility of the equipment to the use and occupation of the land, as well to its adequacy to the rules of Urban Planning concerning Transport Planning in the physical, natural, political, legal and socio-economical ambience. A close examination of a Dry Port - EADI Ribeirão Preto -, its important relation to the urban area where it is placed, the moving of freight and services offered there taking into account the direct and indirect economic costs for different activities, above all the costs and impacts related to the natural, social and economic ambience, is a part of a diagnosis to be elaborated from the urban functioning quality indicators. The problems in the Dry Ports location lead to the formulation of strategic planning guidelines for the use and occupation of land, which may help minimize environmental impact from storing, handling, distribution and transportation activities. The results brought forth in this work may be of great relevance and usefulness to the government in the formulation of a legal and regulative policy to the business park, longing for better strategic decisions. The present work brings forth data, images, maps, tables, charts, among other kinds of information, which makes its reading more dynamic and understandable in its theoretical discussion.

En raison des problèmes d'instabilité à moyen termes des cellules solaires à colorant (DSSC), l'électrolyte liquide à base d'iodure a été remplacé par plusieurs types de matériaux solides transport de trous (HTM) pour obtenir des DSSCs à l'état solide (s-DSSCs). Parmi ces matériaux, l’utilisation des polymères conducteurs(PC) a attiré une attention considérable en raison de leur bonne stabilité, de leur haute conductivité et de la facilité de leur dépôt sur le semi-conducteur mésoporeux TiO2. Dans ce travail de thèse, plusieurs s-DSSCs basées sur des PC utilisés comme HTM ont été développés dans le but d'améliorer leurs performances photovoltaïques en tenant compte des deux objectifs suivants: (i) l'optimisation des processus de transfert inter facial de charge dans la cellule solaire, et (ii) l'optimisation du transport de charge dans le semi-conducteur d'oxyde de type n. Pour atteindre ces objectifs, chaque composant de la s-DSSC a été modifié afin d'étudier son effet sur les performances du dispositif final. En première tentative, une étude analytique est réalisée en faisant varier le sensibilisateur afin de déterminer les fragments de la structure du colorant, qui ont un effet important sur le processus de photopolymérization électrochimique in-situ (PEP) à la fois en milieu organique et en milieu aqueux mais aussi sur les performances des s-DSSCs. Sur la base de ces résultats, un nouveau concept a été développé et consiste en la suppression totale de l'interface entre le colorant et le HTM. Ceci est obtenu par la synthèse de nouveaux colorants liés de façon covalente à un monomère électroactif qui est co-polymérisé par la PEP in-situ. Le copolymère résultant, utilisé comme HTM, est lié de manière covalente au colorant. En outre, la nature de la liaison chimique, reliant le résidu triphénylamine TPA au monomère, est également étudiée comme un facteur clé dans les performances de s-DSSC. En outre, et pour optimiser les processus de transport de charges dans ce type de s-DSSC, de nouvelles s-DSSC basées sur ZnO ont été réalisées et étudiées. / Due to instability problems of dye sensitized solar cells (DSSCs) in longtime uses, the iodine based liquidelectrolyte has been replaced by several types of solid hole transporting materials (HTM) to perform solidstate DSSCs (s-DSSCs). Among them, the substitution by conducting polymers (CP) has attractedconsiderable attention because of their good stability, high hole-conductivity and simple deposition withinthe mesoporous TiO2 semiconductor. In this thesis work, several s-DSSCs based on CPs used as HTM havebeen developed in order to improve their photovoltaic performances taking into account the following twoobjectives: (i) the optimization of the interfacial charge transfer processes within the solar cell, and (ii) theoptimization of the charge transport within the n-type oxide semiconductor. To reach these goals, eachcomponent that constitutes the device was varied in order to investigate its effect on the device’sperformances. As first attempt, an analytical study is carried out by varying the sensitizer in order todetermine the fragments of the dyes structures, that have an important effect on the in-situ photoelectrochemical polymerization process (PEP) both in organic and in aqueous media and hence on theperformances of the s-DSSCs. Based on these results, a new concept of removing completely the interfacebetween the dye and the HTM is developed. This is achieved by the synthesis of new dyes covalently linkedto an electroactive monomer which is co-polymerized by in-situ PEP. The resulting co-polymer, used asHTM, is covalently linked to the dye. In addition, the nature of the chemical bond linking the triphenylamineresidue TPA to the monomer is also investigated as a key factor in the s-DSSCs performances. Besides, andto optimize the charge transport processes within this type of s-DSSC, the elaboration of novel ZnO baseds-DSSCs has been achieved and investigated.

Dans les cellules photovoltaïques organiques, le matériau utilisé pour le transport de trous entre la couche active et l'électrode, est généralement un polymère dopé, dont la stabilité peut être problématique. L'objectif de cette thèse a été de développer des matériaux inorganiques, a priori plus stables, pour remplacer les couches de polymères de transport de trous, tout en restant compatible avec les méthodes de dépôts par voie liquide. L'utilisation de nanoparticules dispersées en solution a été choisie car cela permet le dépôt à basse température, sans nécessité de conversion vers une couche fonctionnelle, contrairement aux voies sol-gel. Le premier objectif de ce travail a donc été l'obtention de nanoparticules d'oxyde de tungstène, hydraté ou non, et de thiocyanate de cuivre. Une synthèse de chauffage assisté par micro-ondes a été utilisée pour l'oxyde de tungstène, permettant d'obtenir des nanoparticules de 30 nm et monodisperses. Pour le thiocyanate de cuivre, il a été choisi de travailler par broyage. Les paramètres du broyage ont été optimisés pour obtenir des particules avec la plus faible distribution en taille possible. Le dépôt de ces dispersions de nanoparticules a permis l'obtention de couches minces et la caractérisation de leurs propriétés optoélectroniques, et notamment du travail de sortie, qui s'est révélé adapté pour une utilisation en dispositif. Des cellules solaires organiques de structures standard et inverse incorporant ces matériaux ont ensuite été réalisées. De bonnes performances ont été obtenues avec une couche active à base de P3HT, notamment en structure inverse où la possibilité d'utiliser le thiocyanate de cuivre a été démontrée pour la première fois. Le suivi des performances sous éclairement et atmosphère contrôlée a également été effectué et a montré un vieillissement rapide pour ces cellules comparées aux cellules de référence à couche de transport de trous polymère. / In organic solar cells, a doped polymer is the most used material for hole transport between the active layer and the electrode, but his stability can be an important issue. The goal of this PhD thesis was to develop inorganic materials, expected to be more stable, in order to replace polymer based hole transporting layers. Another requirement was to keep the compatibility with solution-based deposition methods. The target was to develop nanoparticle dispersions, deposited at low temperature and giving directly a functional layer, without the need of further treatments which are usually required via sol-gel processes. A first objective of the present work was thus the elaboration of nanoparticles of tungsten oxide, hydrated or non-hydrated, and copper thiocyanate. A microwave-assisted heating synthesis has been used for tungsten oxide, leading to mono-dispersed particles around 30 nm. Concerning copper thiocyanate, a ball milling technique has been chosen. The process parameters have been optimized to obtain nanoparticles to narrow the size distribution as much as possible. The deposition of the nanoparticles has allowed the formation of thin layers and the characterization of their optoelectronic properties, such as work function, which was shown to be a relevant parameter for a use in devices. Organic solar cells with standard or inverted structures have been fabricated using these materials as a hole transporting layer. Good photovoltaic performances have been obtained, especially in the inverted structure, in which the possibility to use copper thiocyanate has been demonstrated for the first time. Ageing experiments under light in a controlled atmosphere have also been carried out and have shown a rapid drop in performances for these cells compared to cells incorporating polymer based hole transport layers.

Drug transport across cells and cell membranes in the human body is crucial for the pharmacological effect of drugs. Active transport governed by transport proteins plays an important role in this process. A vast number of transport proteins with a wide tissue distribution have been identified during the last 15 years. Several important examples of their role in drug disposition and drug-drug interactions have been described to date. Investigation of drug-drug interactions at the transport protein level are therefore of increasing interest to the academic, industrial and regulatory research communities. The gene expression of transport proteins involved in drug transport was investigated in the jejunum, liver, kidney and colon to better understand their influence on the ADMET properties of drugs. In addition, the gene and protein expression of transport proteins in cell lines, widely used for predictions of drug transport and metabolism, was examined. The substrate and inhibitor heterogeneity of many transport proteins makes it difficult to foresee whether the transport proteins will cause drug-drug interactions. Therefore, in vitro assays for OCT1 and OATP1B1, among the highest expressed transport proteins in human liver, were developed to allow investigation of the inhibitory patterns of these proteins. These assays were used to investigate two data sets, consisting of 191 and 135 registered drugs and drug-like molecules for the inhibition of OCT1 and OATP1B1, respectively. Numerous new inhibitors of the transport proteins were identified in the data sets and the properties governing inhibition were determined. Further, antidepressant drugs and statins displayed strong inhibition of OCT1 and OATP1B1, respectively. The inhibition data was used to develop predictive in silico models for each of the two transport proteins. The highly polymorphic nature of some transport proteins has been shown to affect drug response and may lead to an increased risk of drug-drug interactions, and therefore, the OCT1 in vitro assay was used to study the effect of common genetic variants of OCT1 on drug inhibition and drug-drug interactions. The results indicated that OCT1 variants with reduced function were more susceptible to inhibition. Further, a drug-drug interaction of potential clinical significance in the genetic OCT1 variant M420del was proposed. In summary, gene expression of transport proteins was investigated in human tissues and cell lines. In vitro assays for two of the highest expressed liver transport proteins were used to identify previously unknown SLC transport protein inhibitors and to develop predictive in silico models, which may detect previously known drug-drug interactions and enable new ones to be identified at the transport protein level. In addition, the effect of genetic variation on inhibition of the OCT1 was investigated.

In vivo studies of hepatobiliary disposition are challenging. The hepatobiliary system is complex, as its physiological localization, complex cellular structure with numerous transporters and enzymes, and the interindividual variability in protein expression and biliary flow will all affect the in vivo disposition of a drug under investigation. The research included in this thesis has focused on the involvement of hepatic transport proteins in the hepatobiliary disposition of rosuvastatin. The impact that several transport inhibitors had on the pharmacokinetics of rosuvastatin was investigated in healthy volunteers and in pigs. The effects were considerable, following inhibition of sinusoidal transport proteins by cyclosporine and rifampicin. These inhibitors significantly reduced the hepatic extraction of rosuvastatin by 50 and 35%, respectively, and the plasma exposure increased by factors of 9.1 and 6.3, respectively. Drug-drug interactions (DDI) resulting in markedly higher plasma exposures are important from a drug safety perspective as increased extrahepatic exposure of statins is associated with an increased risk of severe side-effects, such as myopathy which in rare cases could develop into rhabdomyolysis. The DDI caused by cyclosporine and rifampicin can probably be attributed to inhibition of hepatic uptake transporters. In contrast, inhibition of canalicular transporters by imatinib did not significantly affect the pharmacokinetics of rosuvastatin, which suggests that the intracellular concentration of the inhibitor in the hepatocyte was insufficient to affect the transport of rosuvastatin, or that imatinib is not a sufficiently potent inhibitor in vivo. Furthermore, gemfibrozil administered as a single dose into the jejunum in healthy volunteers and pigs did not affect the plasma or biliary pharmacokinetics of rosuvastatin. The previously reported DDI in humans upon repeated dosing with gemfibrozil might be explained by the accumulation of metabolites able to affect the disposition of rosuvastatin. The investigations presented in this thesis conclude that transport proteins are of considerable importance for the hepatobiliary disposition of rosuvastatin in vivo. The Loc-I-Gut catheter can be applied for the investigation of biliary accumulation and to determine bile specific metabolites, however it has limitations when conducting quantitative measurements. In the porcine model, hepatic bile can be collected for up to six hours and enables the determination of the hepatic extraction in vivo.

Darbo tikslas. Ištirti ir išanalizuoti mokinių vežiojimo būklę Raseinių rajone. Tyrimo medžiaga ir metodai. Anoniminės apklausos būdu pagal specialiai parengtą anketą apklausti 1551 Raseinių rajono mokiniai gyvenantys toliau kaip 3 km nuo mokyklos. Vežiojimo būklė analizuota pagal mokinių gyvenamo atstumo nuo mokyklos, būdą, kuriuo pasiekia mokyklą. Anketinio tyrimo duomenys sukaupti duomenų bazėje ir analizuoti „Excel“ programa. Statistiniai ryšiai nustatyti „SPSS 14.0 for Windows“ programa naudojant neparametrinį chi kvadrato ((2) kriterijų bei Spirmeno koreliacijos koeficientą. Statistinis reikšmingumas nustatytas taikant Stjudento (t) kriterijų. Rezultatai. Raseinių rajono apklausos duomenys rodo, kad 20 proc. mokinių, turinčių teisę į nemokamą pavežėjimą iki artimiausios mokyklos, nėra vežiojami. Didžioji dalis mokinių į mokyklą vežiojami mokykliniais/geltonaisiais autobusiukais. 43,3 proc. Raseinių rajono mokinių kelionės trukmė išsitenka intervale nuo 15 min. iki 30 min. 40,9 proc. mokinių nuo mokyklos gyvena 3-5 km intervale. Pamokų pradžios iki 15 min. laukia 63,1 proc. visų apklaustų mokinių. Pagrindinės problemos, su kuriomis susiduria Raseinių rajono mokiniai, važinėjantys į mokyklą įvairaus tipo autobusais, yra grūmimasis lipant į autobusus bei sėdimų vietų trūkumas juose. Merginos dažniau grumiasi lipant į autobusus nei vaikinai. Jos taip pat dažniau nei berniukai įžeidinėja viena kitą, apsistumdo laukdamos autobuso, skriaudžia jaunesnes. 67,2 proc... [toliau žr. visą tekstą] / Objective. To investigate and analyze the state of conveying pupils in Raseiniai District. Material and methods. 1551 Raseiniai district pupils, who live further than 3 km from the school, was interviewed by a specially prepared anonymous questionnaire. The state of conveying analyzed under the distance from pupils home to school and by the way, how they reaches the school. Questionnaire material has been accumulated in the database and analyzed in the Excel program. Statistical relations determinet by "SPSS 14.0 for Windows" program using nonparametric test, chi-Square (2) and Spirmen‘s correlation coefficient. Statistical significance determined using Student‘s (t) coefficient. Rezults. Survey shows that 20 percent of pupils who having the right to travel free into the nearest school, and come back to the home, is not moved. Most part of the pupils in the school moved by school / yellow bus. 43,3 percent Raseiniai district pupils trip to school takes from 15 until 30 minutes. 40,9 percent pupils live 3-5 kilometers from school. 63,1 percent of all the surveyed pupils waiting about 15 minutes until the start of lessons. The main problems faced by the Raseiniai district pupils, traveling at different school buses, are pushing trying to enter the bus and the lack of passenger seats. Girls pushing trying to enter the buses more often than boys. They also are more often taunt each other. 67,2 percent Raseiniai district pupils who living more than 3 km from the school... [to full text]