Le PAF (facteur d'activation des plaquettes) est un médiateur lipidique de l'inflammation très puissant impliqué dans plusieurs conditions pathophysiologiques.Le PAF agit principalement via un seul récepteur, le PAFR qui appartient à la famille des récepteurs couplés aux protéines G, les GPCRs. Le"two state model" assume que les GPCRs existent dans un état d'équilibre entre un état inactif (R) et un état actif (R*). L'isomérisation de R vers R* peut arriver de façon spontanée, c'est à dire indépendamment de la liaison d'un agoniste. Dans ces travaux de recherche, nous avons tenté de déterminer la propriété antagoniste et agoniste inverse des molécules orthostériques (WEB2086, PCA4248, FR49175, bromure d'octylonium, CV3988 et le Trans BTP dioxolane) à activer la voie des MAPK ainsi que le cycle biochimique des inositols phosphates dans la lignée cellulaire HEK 293 transfectée de façon stable avec le récepteur du PAF. De plus, l'activité potentiellement allostérique sur le PAFR de modulateurs synthétiques tels le THG-315, le THG-316 et MAREK a également été investiguée dans la même lignée cellulaire. Finalement, des surnageants d'hybridome 9H1/1C1, 9F5/1H4, 9F5/1H4, 9F5/1F8, 9F5/2B3 et 9F5/2E4 contenant des anticorps monoclonaux, dirigés tous contre un peptide qui équivaut à la région C-terminale de la troisième boucle extracellulaire du PAFR: GFQDSKfHQA ont également été utilisés, afin : (1) de déterminer le meilleur clone en terme d'affinité et de spécificité et (2) effectuer des tests pour savoir s'ils possèdent des propriétés agonistes ou antagonistes sur le PAFR. En conclusion, les résultats obtenus nous indiquent que : (1) l'efficacité des molécules orthostériques à antagoniser les réponses induites par le PAF dépend de leur nature et de leur concentration, (2) les modulateurs potentiellement allostériques utilisés ne modulent aucune des voies majoritairement connues pour être activées par le PAFR, et (3) qu'il n'y a aucun marquage spécifique du PAFR avec les surnageants d'hybridomes utilisés.

This master´s thesis is focused on efficient control of quality economy in an international company operating in the Czech Republic. It relates to standard and modern concept of quality economy management and theoretical basis of cost management related to quality. The purpose of this thesis is to define, choose and implement the best model of monitoring quality related costs. As a part of the implementation phase of the chosen model, project plan including risk analyses which belongs to individual project's phases will be created, cost related actions defined and in the next phase evaluated and optimized.

Le choc anaphylactique est une réaction allergique systémique qui survient en quelques minutes et pouvant être fatale. Mon travail de thèse s’articule autour de deux projets dont la finalité est de mieux comprendre le mécanisme physiopathologique. La première partie de ce travail consiste à étudier in vivo chez la souris les contributions des récepteurs Fc aux IgG (FcγRs), des cellules effectrices et des médiateurs contribuant dans un modèle d’anaphylaxie systémique passive induit par une sous-classe particulière d’IgG : des IgG1, des IgG2a ou des IgG2b monoclonales dirigées contre un même antigène. Cette étude a permis de démontrer que le FcγRIII, les neutrophiles et les monocytes/macrophages sont les acteurs majoritaires quelque soit la sous-classe d’IgG de souris ; en revanche, la participation des basophiles ainsi que la contribution relative des médiateurs histamine et PAF sont dépendantes de la sous-classe d’IgG utilisée. La deuxième partie de ce travail consiste à étudier plus particulièrement la population plaquettaire dans un modèle de souris humanisées. Contrairement à la souris, les plaquettes humaines expriment un FcγR, le FcγRIIA déjà identifié comme acteur clé de l’anaphylaxie. Un modèle de choc allergique induit par des IgG humaines dans des souris transgéniques pour le FcγRIIA m’a permis de tester l’hypothèse suivant laquelle les plaquettes participent à l’initiation et/ou à la propagation de la réaction. Ce modèle a permis de mettre en évidence une thrombocytopénie sévère, des complexes plaquettes-leucocytes circulants et de montrer que le transfert de plaquettes ou de leur surnageant restaure les signes cliniques du choc allergique. / Anaphylaxis is a systemic hyperacute allergic reaction that occurs within minutes and can be fatal. The aim of my PhD project is to investigate the physiopathological mechanisms underlying anaphylaxis induction. The first part of my work focused on the contribution of FcγRs, effector cells and mediators in passive murine models of systemic anaphylaxis induced by the different subclasses of mouse specific IgG ; directed against the same antigen: IgG1, IgG2a or IgG2b. This study demonstrated that FcγRIII, neutrophils and monocytes/macrophages are the key players of anaphylaxis induction whatever the mouse IgG subclasses used. On the contrary, basophil participation and the relative contribution of histamine and PAF are IgG subclass dependent. The second part of this work examined the role of platelets in anaphylaxis using a humanized mouse model. Opposing the murine situation, human platelets express an IgG receptor, FcγRIIA. This receptor has already been identified as a key player in anaphylaxis. Using aggregated human IgG to induce anaphylaxis in mice transgenic for FcγRIIA, we tested our hypothesis that platelets contribute to the initiation and/or the propagation of this reaction. Anaphylaxis in this model was accompanied by a severe thrombocytopenia, the presence of circulating platelet-leukocyte complexes and activated platelets. I further demonstrated that the transfer of platelets or their activated supernatent into resistant mice restored features of anaphylactic shock.

No description available.

The quality of products is the biggest competitive advantage that a company can achieve. The definition states that quality is the degree of compliance requirement with a set of inherent characteristics. The importance of quality have very increased in recent years - quality is a decisive factor for stable economic growth of enterprises, management quality is the most important protective factor of the loss of markets, quality is a major source of saving materials and energy, the quality affects of macroeconomic indicators, the quality is a limiting factor for the sustainable development , quality and consumer protection are connected vessels. Quality costs are the total costs incurred by producers, users and companies associated with the quality of the product. The quality costs of the manufacturer is divided into four basic groups: the costs of prevention, assessment, costs of external defects and internal defects.

Atualmente, os edifícios selados hermeticamente e com as chamadas \"peles de vidro\" estão presentes em diversos países, e possuem, como consequência, um elevado consumo de energia elétrica para conseguir manter o conforto ambiental dos usuários. Contudo, é possível se beneficiar de uma maior eficiência energética nesses espaços através da combinação de soluções ativas e passivas. Esse estudo tem como objetivo principal avaliar a influência de parâmetros de projetos, tais como o formato da sala, tamanho e orientação das aberturas na fachada, no consumo de energia e no conforto visual em saletas comerciais com ventilação híbrida e integração da iluminação natural com a artificial na cidade de São Paulo. As saletas comerciais analisadas possuem uma área média, diferentes formatos e diferentes aberturas em uma só fachada, representando a solução arquitetônica mais comum encontrada nesse tipo de edifício. Através de análise energética realizada por meio do programa EnergyPlus e da análise lumínica com o programa DIVA-for-Rhino, verificou-se que o formato da sala é essencial para a decisão de um percentual de área de abertura na fachada (PAF) que consuma menos energia. Os resultados mostraram que o uso da ventilação híbrida sempre representou uma economia, atingindo uma redução de até 51% do consumo do ar condicionado para resfriamento e até 26% do consumo de energia total, com os PAF´s de 40, 70 e 100%. Seria interessante considerar elementos de proteção solar que não diminuam a eficácia da ventilação e iluminação naturais nesses ambientes, para se aliar o baixo consumo de energia com menores riscos de ofuscamento. Desta forma, o trabalho auxilia a incorporação destas estrategias para uma maior economia de energia no desenvolvimento do projeto arquitetônico desta tipologia de edifício comercial. / Nowadays, sealed airtight office buildings and so-called \"glass curtain wall\" are present in many countries, and have as a result a high consumption of electric energy to be able to maintain the environmental comfort of the users. However, the combination of passive and active strategies could improve the energy efficiency in these spaces. This study aims to evaluate the design parameters influence, such as rooms shape, the openings size and orientation, in the energy consumption and in the visual comfort in cellular offices with hybrid ventilation system and the integration of daylight and artificial lighting in São Paulo. The analyzed cellular offices have an average area, different shapes and different openings in one facade, representing the more common architectural characteristics found in this type of building in that context. Energy analyses in EnergyPlus and daylight studies using DIVA-for-Rhino were conducted. It was found that the rooms shape is essential for the determination of the window-to-wall-ratio (WWR) for reducing energy consumption. The results showed that the hybrid ventilation use always represented an economy, reaching reduction values up to 51% in the consumption of air conditioning for cooling and up to 26% in cellular offices total consumption, with a WWR of 40, 70 and 100%. It would be interesting to consider sun shading elements that do not reduce the effectiveness of natural ventilation and daylighting in these environments to combine low power consumption with a lower risk of glare. In this way, the work helps the incorporation of these strategies for save energy in the development of the architectural design of this type of commercial building.

Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is one of the leading causes of death due to a single infectious agent and results in more than 1 million human deaths every year. M.tb infection of the host initiates a local inflammatory response, resulting in the migration of a number of host plasma protein and non-protein factors to the site of infection. In addition, some of these factors are also produced locally at the site of infection. It is envisaged that these host factors are likely to come in direct contact with M.tb and immune cells and may modulate the outcome of the infection. In this study, a number of host factors including transferrin, lactoferrin, fibrinogen, C-reactive protein, alpha-2-macroglobulin (α2M), vitronectin, plasminogen, low-density lipoprotein (LDL), high-density lipoprotein (HDL), serotonin, L-alpha dipalmitoyl phosphatidylcholine (DPPC) and platelet activating factor C-16 (PAF C-16) were screened in vitro for their direct effect on the growth of mycobacteria using M.smegmatis as a model. As a result of this screening, PAF C-16, a phospholipid compound was identified that directly inhibited the growth of M.smegmatis and M.bovis BCG in a dose and time-dependent manner. Use of a range of PAF C-16 structural analogues, including Lyso-PAF, PAF C-18, Hexanolamino PAF, 2-O-methyl PAF & Pyrrolidino PAF, revealed that small modifications in structure did not alter the direct growth inhibition property of PAF C-16 and similar levels of M.smegmatis and M.bovis BCG growth inhibition were observed as compared to PAF C-16. Structural dissection of PAF C-16 suggested that the attachment of carbon tail to the glycerol backbone via ether bond at sn-1 position was important for its direct growth inhibition activity against mycobacteria. Microscopy and flow cytometry with PAF C-16 treated M.smegmatis and M.bovis BCG showed damage to the bacterial cell membrane. The addition of membrane-stabilizing agents, α-tocopherol, tween-80 and tween-20, partially mitigated the growth inhibitory effect of PAF C-16. These results suggested that the growth inhibition activity of PAF C-16 against mycobacteria is most likely due to its detergent-like effect, resulting in damage to the bacterial cell membrane. PAF C-16 and its structural analogues were also investigated for their effect on the growth of intracellular M.smegmatis inside THP1 cells. In vitro, PAF C-16, PAF C-18 and Hexanolamino PAF inhibited the growth of intracellular M.smegmatis, whereas, analogues such as Lyso-PAF and 2-O-methyl PAF failed to show any growth inhibitory effect, suggesting that the presence of acetyl group at sn-2 position was important for growth inhibition of intracellular M.smegmatis. Use of PAF receptor antagonists partially mitigated the inhibitory effect of PAF C-16 on the growth of intracellular M.smegmatis, suggesting this inhibition was through receptor-mediated signalling pathways. Blocking of PAF C-16 signalling pathway components such as phospholipase C and phospholipase A2, resulted in the increased survival of intracellular M.smegmatis. Arachidonic acid, a product of PAF C-16 signalling pathway directly inhibited the growth of M.smegmatis. Furthermore, inhibition of iNOS enzyme and antibody-mediated neutralization of TNF-α partially mitigated the inhibitory effect of PAF C-16 on intracellular M.smegmatis growth, suggesting that the production of NO and TNF-α were also involved in PAF C-16 induced intracellular growth inhibition. Overall, this study has identified PAF C-16, its structural analogues such as Lyso-PAF, PAF C-18, Hexanolamino PAF and other compounds including 1-O-hexadecyl-sn-glycerol, miltefosine and hexadecyl lactate with novel anti-mycobacterial activity. Further investigations are needed to demonstrate their effectiveness against M.tb both in vitro and in animal models to assess their therapeutic potential as anti-TB drugs.

Made available in DSpace on 2016-12-12T20:27:39Z (GMT). No. of bitstreams: 1 Jean Carlo da Cunha.pdf: 16855564 bytes, checksum: 337fd862ee9c2affb80cdde33c7439e5 (MD5) Previous issue date: 2015-08-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este trabalho apresenta um esquema de controle de um Compensador Estático para rede de Distribuição (DSTATCOM), utilizado para regular a magnitude da tensão no ponto de acoplamento de carga (PAC) e também possui a função de eliminar harmônicas de tensão através da detecção da tensão no PAC. A regulação da magnitude da tensão é efetuada através da injeção de corrente em quadratura no PAC e a mitiga ção de harmônicas é efetuada através da leitura da tensão do PAC e geração de correntes harmônicas capazes de compensar as distorções na tensão do PAC, sem a necessidade da leitura de corrente da rede ou da carga. O regulador é implementado através de um conversor VSI trifásico à quatro os conectado em paralelo com a rede de distribuição. A potência ativa drenada pelo conversor é somente para suprir suas perdas e controlar a tensão do barramento CC. Este trabalho possui resultados de simulação para o sistema completo bem como resultados experimentais.

The aim of the "Quality management system in the selected company" dissertation work is an analysis of the current situation of the quality management system in a company and make suggestions to improve the current system. For my dissertation work I have chosen engineering company Motorpal, a. s., which is the engineering company and the one of the leading producers of devices for diesel engines to tractors, ships and construction machine.The work consists of two parts, theoretical and practical. The first part describes terms like quality, importance of quality, factors that affect quality, management principles of quality, economy of quality, quality in pre-production stages, quality planning and quality control tools. The second part is primarily focused on the quality costs, which is the most problematic part of the quality management in the company. In this part of the dissertation work is also briefly described the company and its history, company's production program and customers and company's financial situation, processes and quality management system.

Diploma thesis deals with quality management system. The aim of the thesis is to analyze the current situation of quality management system in the selected company. Based on the results possible improvements of the system are designed. The selected company is Banes, s.r.o. situated in Soběslav.