O ibuprofeno é um antiinflamatório não esteróide, com baixa solubilidade em água, que apresenta diversos efeitos colaterais, incluindo lesão gástrica e intestinal. Esses efeitos podem depender da interação com a membrana celular, o que nos motivou a investigar, na primeira parte deste trabalho, a incorporação do ibuprofeno em monocamadas de Langmuir como modelos de membrana celular. Monocamadas de dipalmitoil fosfatidil glicerol (DPPG) e dipalmitoil fosfatidil colina (DPPC) co-espalhadas com o ibuprofeno ou depositadas sobre subfases contendo o fármaco foram estudadas por meio das isotermas de pressão e potencial de superfície. Foram observados efeitos significativos para monocamadas de DPPC, particularmente na transição de fase líquido-expandida para líquido-condensada, com modificações relevantes na elasticidade da monocamada. Esses efeitos aumentaram com a concentração do ibuprofeno. Para os dois tipos de fosfolipídios, o ibuprofeno pôde penetrar na região hidrofóbica, o que foi confirmado por espectroscopia de reflexão e absorção no infravermelho com modulação da polarização (PM-IRRAS), indicando assim a presença de interações hidrofóbicas. A análise por microscopia no ângulo de Brewster (BAM) mostrou que o ibuprofeno impede a formação de grandes domínios de DPPC, enquanto que não foram observadas alterações significativas para o DPPG. A interação entre o ibuprofeno e o DPPG também foi confirmada após a imobilização da monocamada mista em filmes LB com alterações na absorção no UV-Vis da molécula de ibuprofeno. No que diz respeito às implicações biológicas, a ação farmacológica que depende diretamente da interação com a membrana deve ocorrer primeiramente em regiões neutras via penetração do ibuprofeno na região hidrofóbica da membrana celular. A segunda parte deste trabalho foi dedicada à interação de capsaicinóides extraídos da pimenta malagueta com monocamadas de Langmuir constituídas de DPPG e DPPC. A capsaicina é um potente analgésico de uso tópico, que pode causar dessensibilização no local de aplicação dependendo da dose e, portanto há interesse na sua incorporação em sistemas de liberação controlada, como os lipossomos. A técnica de Langmuir foi empregada para verificar essa possibilidade. Os capsaicinóides expandiram as monocamadas de DPPG e aumentaram sua elasticidade. As isotermas de potencial de superfície indicaram que os capsaicinóides provocam aumento de 10% no momento de dipolo numa concentração de 30% em mol. Para os filmes mistos de DPPC e capsaicinóides, a área mínima diminuiu e a elasticidade da monocamada aumentou. De acordo com as isotermas de potencial, os momentos de dipolo diminuíram para as monocamadas de DPPC independentemente da concentração de capsaicinóides. Esses resultados sugerem que as moléculas de DPPC são solubilizadas para a subfase na presença do fármaco. A partir destes resultados, conclui-se que os capsaicinóides podem ser incorporados em estruturas lipídicas, constituídas principalmente de DPPG, o que é relevante para uso em sistemas de liberação de fármacos. / Ibuprofen is a nonsteroidal anti-inflammatory drug, with low solubility in water, which exhibits side effects including gastric and intestinal injury, often irreversible. Some of these effects may depend on the interaction with the cell membrane, which motivated us to investigate the incorporation of ibuprofen in Langmuir monolayers as cell membrane models, in the first part of this thesis. Dipalmitoyl phosphatidyl choline (DPPC) or dipalmitoyl phosphatidyl glycerol (DPPG) monolayers co-spread with ibuprofen or deposited on ibuprofen-containing aqueous subphases were studied using surface pressure and surface potential isotherms. Significant effects were observed for DPPC monolayers, particularly at the liquid-expanded to liquid-condensed phase transition, with relevant changes in the elasticity of the monolayer. These effects increased with the ibuprofen concentration. For both types of phospholipids, ibuprofen could penetrate into the hydrophobic part of the monolayer, which was confirmed with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), thus indicating the presence of hydrophobic interactions. BAM images showed that ibuprofen prevents the formation of large domains of DPPC, while no significant changes were observed for DPPG. The interaction between DPPG-ibuprofen was also confirmed for deposited layers in the form of LB films, with changes in the ibuprofen UV-Vis absorption. As for the biological implications, the pharmacological action depending directly on the membrane interaction should occur primarily with zwitterionic regions of the membrane via penetration of ibuprofen in the hydrophobic part of the monolayer. The second part of this thesis is dedicated to the interaction of capsaicinoids, extracted from malagueta pepper, with Langmuir monolayers of DPPC and DPPG. Capsaicin is a powerful analgesic of topical use, which can cause desensitization in the application site depending on the dose, and therefore there is interest in its incorporation in drug delivery systems, such as liposomes. The Langmuir technique was employed to verify this possibility. The capsaicinoids expanded the DPPG monolayer and increased its elasticity. Surface potential isotherms indicated that the capsaicinoids increased the average dipole moment by 10 % for 30 mol % of capsaicinoids. For the mixed films of DPPC and capsaicinoids, the minimum area decreased and the elasticity increased. According to the surface potential isotherms, the dipole moments decreased for DPPC monolayers regardless of the capsaicinoid concentrations. These results suggest that the DPPC molecules are solubilized into the subphase in the presence of the drug. From these results, it is concluded that the capsaicinoids can be incorporated into structures as the liposomes constituted mainly of DPPG, which is relevant for use in drug delivery systems.

Les objectifs principaux de cette étude étaient d'acquérir une meilleure connaissance des niveaux d'exposition aux particules fines PM₂.₅ de leur composition chimique et de leurs sources, dans trois villes situées sur la façade littorale de la région du Nord-Pas-de-Calais. Les particules fines ont été collectées dans le cadre de deux campagnes d'échantillonnage menées entre novembre 2010 et avril 2011 (campagne "hiver" à Dunkerque et Boulogne sur Mer ; campagne "printemps" à Dunkerque et Saint Omer). La composition chimique des PM₂.₅ a été déterminée suite à la quantification d'éléments majeurs, d'éléments traces, d'ions hydrololubles et du carbone total. Pour les deux périodes considérées, les concentrations et la composition chimique en PM₂.₅ évoluent en suivant les mêmes tendances sur chacun des sites. L'influence de sources locales a été mise en évidence en comparant l'évolution temporelle et les roses de concentration de certains éléments majeurs et éléments traces, d'un site à l'autre. Cette exploitation a permis de proposer des rapports spécifiques entre éléments, qui peuvent être utilisés comme traceurs de certaines sources anthropiques. Enfin, l'application d'un modèle source-récepteur, basé sur la factorisation matricielle non-négative (NMF), a permis d'identifier les sources principales des PM₂.₅, d'évaluer leur contribution et leur part relative au niveau de chacun des sites étudiés. / The main objectives of this study were to acquire a better knowledge on the exposure level to fine PM₂.₅ particles and on their chemical composition and sources, in three cities located on the littoral facade of the Nord-Pas-de-Calais region. The particles were collected following two sampling campaigns held between November 2010 and April 2011 ("winter" campaign in Dunkerque and Boulogne sur Mer ; "Spring" campaign in Dunkerque and Saint-Omer). The chemical composition of the collected PM₂.₅ was determined through the quantification of major elements, trace elements, water soluble ions and total carbon. For the two considered sampling periods, PM₂.₅ concentrations and chemical composition trends followed similar tendencies at each site. Local sources influence was evidenced throughout a comparison of the chronological evolution and concentration roses of some major and trace elements between the sites. This analysis allowed the suggestion of specific elemental ratios, which can be used as tracers of some anthropogenic sources. Finally, the use of a source-receptor model, based on a non-negative matrix factorization (NMF) method, allowed the identification of the main PM₂.₅ sources as well as the evaluation of their relative contributions in each of the studied sites.

State Air Pollution Regulation Agencies (SAPRAs) issue and enforce permits that limit particulate matter emissions from all sources including layer and broiler facilities, cattle feedyards, dairies, cotton gins, and grain elevators. In this research, a process was developed to determine distances from emitting sources to where the estimated concentrations were less than the National Ambient Air Quality Standards (NAAQS). These distances are a function of emission rates and meteorological conditions. Different protocols were used to develop emission factors for cattle feedyards and layer houses. Dispersion modeling with American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) was conducted to determine the emissions of particulate matter. These data were used to determine the distances from the sources to where the concentrations of particulate matter (PM) would be less than the NAAQS. The current air-permitting process requires that concentrations from a source do not exceed the NAAQS at the property line and beyond for the facility to be in compliance with its permit conditions. Emission factors for particulate matter less than 10 micrometers (PM10) were developed for cattle feedyards using a reverse modeling protocol and Tapered Element Oscillating Microbalance (TEOM) sampler data. Corrections were applied to the TEOM measurements to account for TEOM vs. filter-based low-volume (FBLV) sampler bias and over-sampling of PM10 pre-collectors. Invalid concentrations and dust peaks larger than mean ± 3 times the standard deviation were excluded from this study. AERMOD predictions of downwind concentrations at cotton gins were observed for compliance with 24-hour PM10 and PM2.5 NAAQS at property lines. The emissions from three cotton gins were analyzed at 50 m and 100 m distances. TEOM and FBLV samplers were used to collect 24-hour PM10 measurements inside a laying hen house. The distances to the property lines at which the emissions of PM10 were below the 24-hour average PM10 standards were estimated using AERMOD. The results suggested that the special use of the NAAQS for as the property-line concentration not to be exceeded, could be problematic to agriculture. Emission factors that were comparable of published emission factors were obtained in this study. Large distances to property lines were required when minimum flow rate recommendations were not considered. Emission factors that are representative of the emissions in a particular facility are essential; else facilities could be inappropriately regulated.

This thesis aims to increase knowledge about the usage and relevance of Project Management (PM) methods and tools within start-up companies, with regard to the previous work experience of the entrepreneur. The underdeveloped connection of PM and entrepreneurship will be further explored by following the research question proposed below that guides the study. What PM methods and tools do entrepreneurs apply in the process of launching the business versus the operation of the start-up, especially considering their previous work experience and contact with PM? In order to answer the proposed research question and pursue the set objectives, the thesis is structured as follows. First, the methodology within this study is represented in theoretical and practical form in chapter 2 and 4. Furthermore, the theoretical context in the field is summarized in chapter 3. The topics of traditional PM and agile PM (APM) with their characteristics and tools are portrayed; especially the latter is extensively presented in chapter 3.2 due to the need of flexibility and adaptability in the highly dynamic business environment nowadays, as well as the strong connection between APM and the IT development sector. Existing theories about the topics of entrepreneurship and start-ups are described in the subsequent chapter, whereby a focus is set on the entrepreneur itself and his or her previous work experience. To summarize the existing theory in the fields of PM and entrepreneurship a conceptual framework was created by the researchers of this study in chapter 3.4, which also serves to represent the findings of the study in the concluding chapter. The empirical findings, which are presented in chapter 5, were organized in chronological order of the conducted semi-structured, qualitative interviews with software development start-ups in Sweden. Valuable results for the research areas of entrepreneurship and PM, as well as for the practical usage in those fields could be generated. The summarized results of this qualitative study are summarized and presented in chapter 6, titled empirical analysis. The authors found out that the majority of the contacted start-ups did not plan a lot in the launching phase of the business, in fact, they did not apply specific PM tools. While the business was growing, so did its complexity, which is why the need for applying PM tools became more present. Even though no clear connection between the previous work experience of the entrepreneur and the applied PM tools could be established, it was noticeable that prior exposure to PM made the entrepreneurs more aware of the methods and tools. They specifically looked for some and used them more knowingly. Further drivers for choosing a PM method and tools were recommendations and personal research. Next to the stage and scale of the business, especially the team size, the location of the team members and their familiarity with each other appeared to influence the decision on using specific tools tremendously. In general, it could be detected in this study, that the APM framework was commonly recognized as highly valuable for start-ups and many of the respondents already follow it or want to do so in the future. Moreover, primarily only one or very few tools were applied within the start-ups to not lose track of the business development and keep everything concise.

O ibuprofeno é um antiinflamatório não esteróide, com baixa solubilidade em água, que apresenta diversos efeitos colaterais, incluindo lesão gástrica e intestinal. Esses efeitos podem depender da interação com a membrana celular, o que nos motivou a investigar, na primeira parte deste trabalho, a incorporação do ibuprofeno em monocamadas de Langmuir como modelos de membrana celular. Monocamadas de dipalmitoil fosfatidil glicerol (DPPG) e dipalmitoil fosfatidil colina (DPPC) co-espalhadas com o ibuprofeno ou depositadas sobre subfases contendo o fármaco foram estudadas por meio das isotermas de pressão e potencial de superfície. Foram observados efeitos significativos para monocamadas de DPPC, particularmente na transição de fase líquido-expandida para líquido-condensada, com modificações relevantes na elasticidade da monocamada. Esses efeitos aumentaram com a concentração do ibuprofeno. Para os dois tipos de fosfolipídios, o ibuprofeno pôde penetrar na região hidrofóbica, o que foi confirmado por espectroscopia de reflexão e absorção no infravermelho com modulação da polarização (PM-IRRAS), indicando assim a presença de interações hidrofóbicas. A análise por microscopia no ângulo de Brewster (BAM) mostrou que o ibuprofeno impede a formação de grandes domínios de DPPC, enquanto que não foram observadas alterações significativas para o DPPG. A interação entre o ibuprofeno e o DPPG também foi confirmada após a imobilização da monocamada mista em filmes LB com alterações na absorção no UV-Vis da molécula de ibuprofeno. No que diz respeito às implicações biológicas, a ação farmacológica que depende diretamente da interação com a membrana deve ocorrer primeiramente em regiões neutras via penetração do ibuprofeno na região hidrofóbica da membrana celular. A segunda parte deste trabalho foi dedicada à interação de capsaicinóides extraídos da pimenta malagueta com monocamadas de Langmuir constituídas de DPPG e DPPC. A capsaicina é um potente analgésico de uso tópico, que pode causar dessensibilização no local de aplicação dependendo da dose e, portanto há interesse na sua incorporação em sistemas de liberação controlada, como os lipossomos. A técnica de Langmuir foi empregada para verificar essa possibilidade. Os capsaicinóides expandiram as monocamadas de DPPG e aumentaram sua elasticidade. As isotermas de potencial de superfície indicaram que os capsaicinóides provocam aumento de 10% no momento de dipolo numa concentração de 30% em mol. Para os filmes mistos de DPPC e capsaicinóides, a área mínima diminuiu e a elasticidade da monocamada aumentou. De acordo com as isotermas de potencial, os momentos de dipolo diminuíram para as monocamadas de DPPC independentemente da concentração de capsaicinóides. Esses resultados sugerem que as moléculas de DPPC são solubilizadas para a subfase na presença do fármaco. A partir destes resultados, conclui-se que os capsaicinóides podem ser incorporados em estruturas lipídicas, constituídas principalmente de DPPG, o que é relevante para uso em sistemas de liberação de fármacos. / Ibuprofen is a nonsteroidal anti-inflammatory drug, with low solubility in water, which exhibits side effects including gastric and intestinal injury, often irreversible. Some of these effects may depend on the interaction with the cell membrane, which motivated us to investigate the incorporation of ibuprofen in Langmuir monolayers as cell membrane models, in the first part of this thesis. Dipalmitoyl phosphatidyl choline (DPPC) or dipalmitoyl phosphatidyl glycerol (DPPG) monolayers co-spread with ibuprofen or deposited on ibuprofen-containing aqueous subphases were studied using surface pressure and surface potential isotherms. Significant effects were observed for DPPC monolayers, particularly at the liquid-expanded to liquid-condensed phase transition, with relevant changes in the elasticity of the monolayer. These effects increased with the ibuprofen concentration. For both types of phospholipids, ibuprofen could penetrate into the hydrophobic part of the monolayer, which was confirmed with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), thus indicating the presence of hydrophobic interactions. BAM images showed that ibuprofen prevents the formation of large domains of DPPC, while no significant changes were observed for DPPG. The interaction between DPPG-ibuprofen was also confirmed for deposited layers in the form of LB films, with changes in the ibuprofen UV-Vis absorption. As for the biological implications, the pharmacological action depending directly on the membrane interaction should occur primarily with zwitterionic regions of the membrane via penetration of ibuprofen in the hydrophobic part of the monolayer. The second part of this thesis is dedicated to the interaction of capsaicinoids, extracted from malagueta pepper, with Langmuir monolayers of DPPC and DPPG. Capsaicin is a powerful analgesic of topical use, which can cause desensitization in the application site depending on the dose, and therefore there is interest in its incorporation in drug delivery systems, such as liposomes. The Langmuir technique was employed to verify this possibility. The capsaicinoids expanded the DPPG monolayer and increased its elasticity. Surface potential isotherms indicated that the capsaicinoids increased the average dipole moment by 10 % for 30 mol % of capsaicinoids. For the mixed films of DPPC and capsaicinoids, the minimum area decreased and the elasticity increased. According to the surface potential isotherms, the dipole moments decreased for DPPC monolayers regardless of the capsaicinoid concentrations. These results suggest that the DPPC molecules are solubilized into the subphase in the presence of the drug. From these results, it is concluded that the capsaicinoids can be incorporated into structures as the liposomes constituted mainly of DPPG, which is relevant for use in drug delivery systems.

Made available in DSpace on 2016-03-15T19:30:56Z (GMT). No. of bitstreams: 1 Suzana Gilioli da Costa Nunes.pdf: 1163925 bytes, checksum: aa9c952dffb7a7d62052a6f61929b153 (MD5) Previous issue date: 2012-09-20 / This thesis involved three constructs in the area of organizational strategy, exploration, exploitation and carrying capacity of the organizational knowledge. The main objective was to evaluate the degree of association between exploration and exploitation and absorption capacity. To achieve this main objective, it was formulated three others, the secondary character, for the three constructs involved in the research. From this, twelve specific goals and two hypotheses were stated. For the achievement of general and specific objectives of this thesis it was developed a quantitative research study, with the level of analysis one hundred companies within the sectors of trade and services, located in the city of Palmas, Tocantins State. The respondents consisted of managers working at these companies. The questionnaire was developed using two scales. One for the measurement of the guidelines for exploration and exploitation, developed by Popadiuk (2012) and the other on the scale was measuring the absorption capacity of knowledge developed by Matusik and Heeley (2005). Statistical analyzes were related to the objectives of descriptive character. To verify the two hypotheses the technique involved the Structural Equation Modeling using software PLS-PM. As the concepts of exploration and exploitation were based on the proposed Popadiuk (2012) which is translated by six dimensions: practices of organizational knowledge, practices, innovation, strategic focus, competition, partnership and efficiency, hence originated six specific objectives. Since the concept of absorption capacity was translated by four specific objectives, in order that one of the dimensions involved two other smaller. The results showed that the companies surveyed have guidance for exploitation. In relation to absorptive capacity, firms have a high degree of predominance of relationship with the environment, routines and procedures and public awareness. However, showed low level in relation to individual abilities. The third goal, which is the association between the two constructs, the results showed that the analysis by structural equation modeling, we can identify the measurement model used was adequate in terms of its convergent validity and discriminant validity . Both hypotheses were confirmed. The absorption capacity knowledge showed a coefficient for explaining operation and exploitation, characterized as the significant level of 1%. The absorption capacity of more influence than the operation guidance for exploitation as ratio between operating and absorption capacity is greater than the coefficient of exploitation identified and absorption capacity. / Esta tese envolveu três construtos da área de estratégia organizacional: exploração, explotação e capacidade de absorção do conhecimento organizacional. O objetivo principal foi avaliar o grau de associação entre exploração e explotação e a capacidade absorção. Para atingir esse objetivo principal, foram formulados três outros, de caráter secundário, referentes aos três construtos envolvidos na pesquisa. A partir disso, doze objetivos específicos e duas hipóteses foram enunciadas. Para o atingimento dos objetivos gerais e específicos desta tese foi desenvolvida uma pesquisa de caráter quantitativo, tendo como nível de análise cem empresas pertencentes aos setores de comércio e de serviços, localizadas na cidade de Palmas, Estado do Tocantins. Os informantes consistiram em gestores que trabalhavam nessas empresas. O questionário aplicado envolveu a utilização de duas escalas. Uma para a mensuração das orientações para exploração e explotação, desenvolvido por Popadiuk (2012) e a outra escala foi referente à mensuração da capacidade de absorção do conhecimento, desenvolvida por Matusik e Heeley (2005). As análises estatísticas relativas aos objetivos foram de caráter descritivo. Para a verificação das duas hipóteses a técnica utilizada envolveu a Modelagem de Equações Estruturais, mediante o software PLS-PM. Como os conceitos de exploração e explotação foram baseados na proposta de Popadiuk (2012) que é traduzida por seis dimensões: práticas de conhecimento organizacional, práticas de inovação, foco estratégico, competição, parcerias e eficiência; daí, originaram-se seis objetivos específicos. Já o conceito de capacidade de absorção ficou traduzido por quatro objetivos específicos, tendo em vista que uma das dimensões envolvia duas outras, menores. Os resultados demonstraram que as empresas pesquisadas possuem orientação para explotação. Já em relação à capacidade de absorção, as empresas possuem alto grau de predominância de relacionamento com o ambiente, rotinas e procedimentos e conhecimento público. Entretanto, apresentaram baixo grau no que se refere às habilidades individuais. Quanto ao terceiro objetivo, que trata da associação entre os dois construtos, os resultados demonstraram que, pela análise, mediante a modelagem de equações estruturais, pode-se identificar que o modelo de mensuração adotado foi adequado em termos de sua validade convergente e validade discriminante. As duas hipóteses foram confirmadas. A capacidade de absorção do conhecimento apresentou um coeficiente de explicação para exploração e para explotação, caracterizados como significantes ao nível de 1%. A capacidade de absorção influencia mais a orientação para exploração do que para explotação dado que coeficiente entre exploração e capacidade de absorção foi maior do que o coeficiente identificado entre explotação e capacidade de absorção.

Ce mémoire rapporte les études de protéines amyloïdes en interaction avec des membranes modèle afin d’établir une relation structure toxicité. Nous avons choisi différents modèles membranaires (monocouches, bicouches) de composition lipidique et charges différentes et utilisé différentes méthodes physico-chimiques afin de caractériser les interactions des protéines amyloïdes avec les membranes.Nous avons montré l’importance de la contribution électrostatique dans les interactions de la protéine amyloïde HET-s (218-289) et ses mutants avec les membranes modèles.L’ellipsométrie a démontré que les mutants toxiques de HET-s (218-289) (M8, WT.Y1Y2V2) perturbentfortement les monocouches lipidiques à l’interface air-eau. La structure riche en feuillets β antiparallèles des protéines àl’interface air-eau et dans l’interaction avec les monocouches de lipides a été démontrée par la spectroscopie PMIRRAS (Polarization Modulation – Infrared Reflection Absorption Spectroscopy). Nous avons établie que l’interface air-eau peut modifier l’agrégation des protéines amyloïdes. A l’aide de la spectroscopie de fluorescence, la spectroscopie PWR (Plasmon-Waveguided Resonance) et la spectroscopie ATR-FTIR (Attenuated Total Reflection – Fourier Transform Infrared), nous avons mis en évidence que la protéine toxique M8 adopte une structure riche en feuillets β antiparallèles en altérant fortement l’intégrité des bicouches lipidiques. Au contraire, la protéine non toxique WT se structure en feuillets β parallèles dans ces interactions et elle ne perturbe pas l’homogénéité des membranes. La toxicité de la protéine M8 semble liée à son organisation différente et à sa capacité à réorganiser les membranes.Nos résultats confortent également l’hypothèse de la toxicité des oligomères amyloïdes.Une étude sur la fabrication d’une cellule microfluidique pour la séparation de différents types d’autoassemblage afin de les détecter et de les étudier en interaction avec des liposomes par spectroscopie infrarouge est présentée. Une cellule microfluidique de CaF2 de 8 μm d’épaisseur de canaux est obtenue et est utilisée pour la détection d’une protéine de test. / This manuscript reports the studies of amyloid proteins in interaction with membrane models in order to establish their structure-toxicity relationship.Membrane models (monolayer, bilayer) of different charge and lipid composition were used. We used various physico chemical methods to characterize the interaction of these amyloid proteins with membranes.We showed the importance of the electrostatic contribution in the interactions of the amyloid protein HET-s(218-289) and its mutants with model membranes.Ellipsometry showed that the toxic mutants of HET-s (218-289) (M8, WT.Y1Y2V2) strongly disturbed thelipid monolayers at the air-water interface. The structure rich in antiparallel β sheets of auto-assembled proteins at theair-water interface and in interaction with lipid monolayers at the air-water interface has been demonstrated by the PMIRRAS spectroscopy (Polarization Modulation - Infrared Reflection Absorption Spectroscopy). We established that theair-water interface can change the aggregation properties of amyloid proteins.By using fluorescence spectroscopy, PWR spectroscopy (Plasmon Resonance-Waveguided spectroscopy) and ATR-FTIR spectroscopy (Attenuated Total Reflection - Fourier Transform Infrared spectroscopy), we found that thetoxic protein (M8) adopted a structure rich in antiparallel β sheets greatly altered the integrity of lipid bilayers. Incontrast, the protein non-toxic (WT) organized in a structure rich in parallel β sheets in these interactions and it did notdisturb the homogeneity of the membranes. The toxicity of the protein M8 appears to be related to its differentorganization and its ability to rearrange membranes.Our results also support the hypothesis of the toxicity of amyloid oligomers.A study on the fabrication of a microfluidic cell for the separation of different aggregation states of amyloidproteins in order to detect these assemblies and to study their interaction with liposomes by infrared spectroscopy is presented. A CaF2 microfluidic cell with channels of 8 μm of thickness was obtained and was used for the detection of atested protein.

Les cryptophanes sont des molécules sphériques pouvant encapsuler dans leur cavité lipophile des molécules neutres (halogénométhanes, xénon) mais aussi des espèces ioniques comme les cations césium et thallium. Notre objectif a été d’immobiliser ces cages moléculaires de manière covalente sur un support solide dans le but de créer un matériau capable d’extraire des cations toxiques comme le thallium en milieu aqueux. Différentes stratégies ont été envisagées pour optimiser l’immobilisation de dérivés du cryptophane-A sur des surfaces de silice et d’or (surfaces planes et nanoparticules magnétiques de type coeur-écorce). Les cryptophanes-A mono-acide (1) et hexa-acide(2) ont été immobilisés sur des surfaces de silice préalablement fonctionnalisées par des groupements amines. Le cryptophane-A alcanethiol (3), ainsi que les cryptophanes 1 et 2 modifiés par lacystéamine (respectivement 4 et 5) ont été immobilisés sur des surfaces d’or. La caractérisation des surfaces planes par spectroscopie infrarouge de réflexion-absorption par modulation de polarisation(PM-IRRAS) a permis d’estimer le taux de recouvrement des différentes monocouches de cryptophanes et, ainsi, d’évaluer la méthode d’immobilisation la plus efficace. Un taux de recouvrement proche de 100% a été obtenu pour le cryptophanes 3 immobilisé sur les surfaces d’or.Ce composé a également été immobilisé de façon très efficace sur des nanoparticules magnétiques(γ-Fe2O3/SiO2) enrobées d’une nano-écorce d’or. Ces résultats permettent d’envisager la synthèse d’un cryptophane portant cinq fonctions hydroxyles et une fonction thiol afin de créer des matériaux capables d’extraire des cations toxiques. / Cryptophanes are spherical molecules that can encapsulate neutral molecules(halogenomethanes, xenon), and ionic species like cesium and thallium cations in their lipophiliccavity. Our objective was to covalently immobilize these molecular cages onto solid substrates tocreate a material able to extract toxic cations such as thallium in aqueous media. Different strategieswere considered to optimize the immobilization of cryptophane-A derivatives onto silica and goldsurfaces (flat surfaces and core-shell magnetic nanoparticles). Mono-acid cryptophane-A (1) andhexa-acid cryptophane-A (2) were immobilized onto silica surfaces that were functionalized by aminogroups beforehand. Alcanethiols cryptophane-A (3), 1 and 2 modified by cysteamine (cryptophanes 4and 5 ,respectively) were immobilized onto gold surfaces. Flat surfaces were characterized bypolarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to estimate thesurface coverage of different cryptophane monolayers and to evaluate the most effective method. Asurface coverage close to 100% was obtained for the cryptophane 3 immobilized onto gold surfaces.This compound has been also immobilized efficiently onto magnetic nanoparticles (γ-Fe2O3/SiO2)coated with gold nano-shell. These results allow to consider the synthesis of cryptophane bearing fivehydroxyl and one thiol functions to create materials able to extract toxic cations

This master’s thesis deals with the determination of conditions and the proposal of appropriate instruments within the World Class Manufacturing system (WCM), mainly its pillars Professional Maintenance (PM), in order to remove, with the assistance of subsequent analysis, all the waste which occurs in the enterprise and consequently to appropriately optimise the activities of staff, especially the specialized engineers.

The aim of this master’s thesis is to analyze ways of propagation light in optical fiber with two polarization planes. Theoretical part is focused to to the issue of polarized light, its mathematical description using Stokes and Jones vectors, the state of polarization on Poincare sphere and polarization multiplex. In the practicle part are first measured several laboratory measurements to verify the theoretical assumptions from the previous chapters. At the end of the thesis was constructed a functional polarization multiplex for wavelength 1550 nm.