Made available in DSpace on 2017-07-21T20:42:44Z (GMT). No. of bitstreams: 1 GUILHERME BACCI.pdf: 2882047 bytes, checksum: 2bf1ae6f64200191aa823e1e72f2a368 (MD5) Previous issue date: 2011-11-28 / Over the years, BaTiO3 has been used in a wide variety of crystal types applications, ceramic structures, multilayer and thin films. Lately, the utilities techniques to obtain BaTiO3 are so diversified and was cited in several works. The picked method for the synthesis of BaTiO3 in this work was the non conventional method called freeze drying, which consist to obtain powders in low temperature. Nanoparticulated powders was produced with pure phase at 973K and characterized as positive temperature coefficient (PTC). / Ao longo dos anos, BaTiO3 tem sido usado numa ampla variedade de aplicações na forma de vários tipos de cristais, estruturas cerâmicas, multicamadas e filmes finos. Recentemente, as técnicas utilizadas pra obtenção do BaTiO3 são muito diversas e foram mencionadas em vários trabalhos. O método selecionado para síntese do BaTiO3 neste trabalho foi o método não convencional chamado liofilização que, são pós obtidos na desidratação dos pós a baixas temperaturas. Foram produzidos pós nanoparticulados com fase pura a 700°C e caracterizados como sensores de temperatura com coeficiente positivo (PTC).

Das Nutzen von 3D-Anmerkungselementen unter PTC Creo-Parametric ermöglicht die Erstellung von 3D-CAD-Modellen mit ausführlichen Informationen zu Funktion, Tolerierung und Fertigung. Dadurch kann der Archivierungs- und Versionspflegeaufwand von Produktdaten und ein besseres, räumliches Verständnis für das Produkt in seiner Entstehungsphase erreicht werden.

Throughout Jönköpings University has a bachelor thesis at Husqvarna AB been done, were the main focus is to develop the existing heating element. On the existing front and rear handle is where the heating element are placed and the material the handles are made of is aluminum respectively plastic. These handle are also called the reference at Husqvarna AB.   To be able to have different type of concepts was a method called concept generating, where these concepts were developed and later on eliminate nonrealistic ideas. During the project there was a lot of visits at several companies to be able to see the production and have a meeting with them. PTC-technology was the chosen heating element for this project and stands for “Positive Temperature Coefficient” and is a self-regulating heating element. PTC has a low inner resistance until it reaches the temperature that it is manufactured for to maintain a more stable heating level. Tests were made on the concepts that was given against the reference to see which concept that is most suitable for further development. Different methods and theories was used to be able to create tools for embossing the front handle, which later on got heat-treated.   The existing heating element is based on the amount of rounds per minute the flywheel rotates which result in different heating levels for the consumer. PTC technology gives a more stable heating level for such system with various rotational speed. Husqvarna AB’s purpose with this thesis is to develop a more stable heating element on the XPG chainsaws.   This thesis ended with a result of two different winning concepts which was given recommendations for how they could further be developed to be possible to replace the existing heating element.

Considerando-se a necessidade brasileira de se obterem fármacos a preços competitivos e usando tecnologia nacional, visamos sintetizar um fragmento do Indinavir empregando como material de partida a L-serina, um aminoácido natural de baixo custo. Desta maneira, desenvolvemos a seguinte rota, em 6 etapas: p-tosilação da serina, pelo uso de cloreto de p-tosila / NaOH; amidação da p-tosilserina, empregando-se o sal de terc-butilamônio da N-hidroxissuccinimida / DCC; ciclização da (S)-2-terc-butil-N-p-tosilserina, em condição de transferência de fase, com cloreto de p-tosila / carbonato de potássio / TEBAC; abertura regiosseletiva do anel da aziridina pela 3-picolilamina; N,N-bis-alquilação da resultante diamina, com triflato de vinildifenilsulfônio e destosilação da piperazina obtida, promovida por HBr 30%, em ácido acético. Deste modo, o fragmento (S)- N-terc-butil-4-(piridin-3-ilmetil)piperazina-2-carboxamida foi obtido em 7 % de rendimento global e pode ser usado em uma rota alternativa para a síntese do Indinavir. / Considering the Brazilian need to obtain drugs at competitive prices and using national technology, we aimed to synthesize a fragment of Indinavir using L-serine, an inexpensive natural amino acid. Thus, we developed the following route in 6 steps: p-tosylation of serine by using p-tosyl chloride / NaOH; amidation of p-tosylserine employing the N-hydroxisuccinimide terc-butylammonium salt / DCC; cyclization of (S)-2-terc-butyl-N-p-tosylserine under phase transfer catalysis with p-tosyl chloride / potassium carbonate / TEBAC; aziridine ring opening with 3-picolylamine; N,N-bisalkylation of the resulting diamine with vinyldiphenylsulfonium triflate and detosylation of the obtained piperazine promoted by HBr 30% in acetic acid. In this way, the (S)-N-terc-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide fragment was obtained in 7 % overall yield and can be used in an alternative route for the synthesis of Indinavir.

Considerando-se a necessidade brasileira de se obterem fármacos a preços competitivos e usando tecnologia nacional, visamos sintetizar um fragmento do Indinavir empregando como material de partida a L-serina, um aminoácido natural de baixo custo. Desta maneira, desenvolvemos a seguinte rota, em 6 etapas: p-tosilação da serina, pelo uso de cloreto de p-tosila / NaOH; amidação da p-tosilserina, empregando-se o sal de terc-butilamônio da N-hidroxissuccinimida / DCC; ciclização da (S)-2-terc-butil-N-p-tosilserina, em condição de transferência de fase, com cloreto de p-tosila / carbonato de potássio / TEBAC; abertura regiosseletiva do anel da aziridina pela 3-picolilamina; N,N-bis-alquilação da resultante diamina, com triflato de vinildifenilsulfônio e destosilação da piperazina obtida, promovida por HBr 30%, em ácido acético. Deste modo, o fragmento (S)- N-terc-butil-4-(piridin-3-ilmetil)piperazina-2-carboxamida foi obtido em 7 % de rendimento global e pode ser usado em uma rota alternativa para a síntese do Indinavir. / Considering the Brazilian need to obtain drugs at competitive prices and using national technology, we aimed to synthesize a fragment of Indinavir using L-serine, an inexpensive natural amino acid. Thus, we developed the following route in 6 steps: p-tosylation of serine by using p-tosyl chloride / NaOH; amidation of p-tosylserine employing the N-hydroxisuccinimide terc-butylammonium salt / DCC; cyclization of (S)-2-terc-butyl-N-p-tosylserine under phase transfer catalysis with p-tosyl chloride / potassium carbonate / TEBAC; aziridine ring opening with 3-picolylamine; N,N-bisalkylation of the resulting diamine with vinyldiphenylsulfonium triflate and detosylation of the obtained piperazine promoted by HBr 30% in acetic acid. In this way, the (S)-N-terc-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide fragment was obtained in 7 % overall yield and can be used in an alternative route for the synthesis of Indinavir.

Gerenderte Animation von kinematisch gekoppelten Komponenten mit Pro/ENGINEER bzw. Creo zur Produktpräsentation oder auch Montageanleitung

Gegenstand der vorliegenden Publikation sind Festigkeitsberechnungen von Maschinen aus der Hütten- und Walzwerkstechnik mit Pro/Mechanica. Erläutert werden die Arbeitstechniken, die bei der Aufbereitung der Modelle zum Einsatz kommen, sowie die genutzten Regelwerke für den Festigkeitsnachweis. Die angeführten Rechenbeispiele stammen allesamt aus der täglichen Praxis der industriellen Nutzung von FE-Methoden im Maschinenbau.

This work is concerned with the design, development and performance evaluation of an inertance Pulse Tube Cryocooler (PTC). The main components of a PTC are the compressor, regenerator, pulse tube and inertance tube coupled to a reservoir. The inertance tube is a key component that affects the pressure and mass flow and phase shift between them and hence the performance. In conjunction with the compressor, it also plays a strong role in determining the frequency of operation. The PTC is designed based on system level numerical models (SAGE and DeltaE), component level thermo-acoustic models (DeltaE) of inertance tube and regenerator and experimental data of earlier fabricated Stirling coolers. As a starting point, an inertance tube with a diameter of 3 mm and 3.1 m long was chosen through component level analysis that provides phase shift of around 50 degrees at a pressure ratio of 1.1 for an acoustic power of about 4 W (in order to achieve 1 W of net cooling at 80 K) at 25 bar mean pressure and 60 Hz. From this inertance tube geometry, an estimate of the mass flow rate at the cold heat exchanger is obtained. Based on this mass flow rate, the initial dimensions of the pulse tube and regenerator are arrived at. A parametric study using system level model is carried out to obtain the maximum COP by varying inertance tube length and regenerator diameter. A flexure bearing compressor consisting of moving coil linear motor coupled to a piston is designed for the above cold head. Based on the above design considerations, the PTC compressor and cold head are fabricated and assembled. The PTC is charged with helium at mean pressure of 25 bar and instrumented with pressure and position transducers, temperature sensors and a skin-bonded heater for simulating the heat load on the cold head. Experimental data for the PTC were obtained with two different inertance tube lengths for different frequencies of operation. The cold head temperature exhibited a minimum with respect to the frequency. This optimum frequency shifts towards lower frequency with increased length of the inertance tube. The experimental data clearly shows that with different inertance tube lengths the optimum frequency locates itself for obtaining zero phase shift at the middle of the regenerator. It is observed that the optimum frequency is closely linked to the natural frequency of the pressure wave in the inertance tube suggesting a standing wave within the inertance tube with the pressure node at the reservoir. Thus the inertance tube is found to be analogous to a quarter wave resonator in a thermo-acoustic device. It may thus be possible to pre-fix an operating frequency for a given PTC cold head by choosing an inertance tube length close to quarter wave resonator length. This study has given insights on the phase shift between pressure and mass flow rate governed by the inertance tube and the connection between the optimum and natural frequencies which can be used for better design of PTCs.

Les cancers papillaires de la thyroïde (PTC) sont les tumeurs endocrines les plus courantes et représentent 2-3% de tous les cancers humains. Les altérations génétiques les plus pertinentes trouvées dans ces tumeurs sont des mutations dans les gènes BRAF et RAS, et des translocations du gène RET. Ces translocations oncogéniques, connues sous le nom de RET/PTC, résultent de la fusion de RET avec des gènes partenaires non-apparentés. L’exposition aux radiations ionisantes est le facteur de risque le plus important pour la formation de RET/PTC. Durant ces dernières années, notre groupe a mis en évidence un rôle crucial des espèces réactives de l'oxygène (ROS) dans la formation de RET/PTC dans des cellules thyroïdiennes in vitro et a notamment montré que l'irradiation (IR) induit l’établissement d’un stress oxydatif persistant du aux ROS produites par la NADPH Oxydase DUOX1, laquelle est induite à post-IR. Cela conduit à des dommages à l'ADN. Les enfants présentent un risque significativement plus élevé de développer des cancers radio-induits de la thyroïde exprimant RET/PTC, probablement en raison du taux de prolifération élevé des cellules. Ceci suggère que la dynamique de réplication pourrait être impliquée dans la formation de la translocation RET/PTC1. En effet, il a été montré que l'induction pharmacologique d’un stress réplicatif peut favoriser la formation de RET/PTC in vitro dans les cellules thyroïdiennes. Ainsi, pour déterminer si un stress réplicatif peut contribuer aux effets à long terme de l'irradiation: à savoir une persistance des lésions de l'ADN et la formation de RET/PTC1, nous avons analysé les effets à post-IR dans les cellules NTHY-ori3.1. Nos résultats confirment qu’une irradiation des cellules aux rayons X à la dose de 5 Gy induit deux vagues de stress oxydatif: une première vague forte mais transitoire qui se produit dans les minutes qui suivent l'irradiation et une deuxième vague dont l’ augmentation débute 2 jours après l'irradiation pour persister ensuite. Ces deux pics de stress oxydatif conduisent à deux pics de dommages à l'ADN. L'irradiation des cellules à cette dose n’a aucun effet sur la prolifération et sur la progression du cycle cellulaire. Cependant, plusieurs marqueurs de stress réplicatif sont exprimés trois jours après l'irradiation. Par ailleurs, l'analyse de la dynamique de réplication révèle une diminution de la vitesse de réplication à post-IR qui est contrecarrée par les antioxydants, suggérant qu’un stress oxydatif peut contribuer à un stress réplicatif. Enfin, par ChIP-QPCR, nous observons que les gènes impliqués dans RET/PTC1 présentent plus de cassures double brin que des gènes endogènes, et ce, trois jours après l'irradiation. Ainsi, nous proposons qu’un stress réplicatif induit par un stress oxydatif pourrait être potentiellement impliqué dans l'étiologie des tumeurs RET/PTC-positives. / Papillary thyroid cancers (PTC) are the most common endocrine tumors and account for 2-3% of all human cancers. The most relevant genetic alterations found in these tumors are mutations in the genes BRAF and RAS, and chromosomal translocations in RET, a proto-oncogene activated in 15-20% of PTCs. These oncogenic translocations, known as RET/PTCs, result from the fusion of RET with unrelated partner genes. Ionizing radiation is a major risk factor for RET/PTC formation, however, the molecular mechanisms involved in these radioinduced translocations just begun to be unveiled. In the past few years, our group has reported a critical role for reactive oxygen species (ROS) in the formation of RET/PTC in thyroid cells in vitro and has also shown that irradiation can elicit a persistent oxidative stress caused by the upregulation of the NADPH Oxidase DUOX1 that leads to DNA damage, mediating at least part of the effects of radiation. However, how could ROS lead to the formation of RET/PTC is not fully understood. Children are at significantly higher risk of developing radio-induced thyroid tumors, specially RET/PTC positive, probably due to the intense proliferation rate of their follicular thyroid cells. This epidemiological observation prompts the assumption that replication dynamics may be involved in RET/PTC formation. Indeed, it has been shown that the pharmacological induction of replicative stress can stimulate the in vitro formation of RET/PTC in thyroid cells. Thus, to investigate whether replicative stress might contribute for the long-term effects of irradiation on DNA damage and RET/PTC formation, we analyzed the effects of radiation in NTHY-ori3.1 thyroid cell lineage in terms of oxidative and replicative stress and replication dynamics. Our results confirm that irradiation triggers two waves of oxidative stress: first, a strong but transient oxidative burst takes place minutes after irradiation and next, a persistently increased oxidative stress that starts only 2 days after irradiation. These two peaks of oxidative stress lead to two peaks of DNA damage. Irradiation caused little or no effect on proliferation nor on cell cycle progression. However, several protein markers of replicative stress, such as pATR, pATM, pChk1 and pRPA are induced three days after irradiation. Moreover, replication dynamics analysis revealed a diminished replication speed that has been reversed by antioxidants, suggesting that oxidative stress may contribute to replication defects. Finally, using ChIP-qPCR, we observed that the genes involved in RET/PTC1 translocation present more double-stranded breaks than RET/PTC-unrelated genes 3 days after irradiation. Hence, we propose that replicative stress is potentially involved in the etiology of RET/PTC-positive tumors. / HECHT, Fabio. The role of reactive oxygen species in thyroid radio-carcinogenesis. Rio de Janeiro, 2018. Doctoral thesis - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil and Université Paris-Saclay, Orsay, France, 2018.O câncer papilífero de tireoide é o tumor endócrino mais comum e corresponde a 2-3% de todos os cânceres humanos. As alterações genéticas mais relevantes relacionadas a esse tumor são mutações nos genes BRAF e RAS e translocações do gene RET, um proto-oncogene ativado em 15-20% dos tumores papilíferos. Essas translocações, conhecidas como RET/PTC, resultam da fusão de RET com diversos outros genes. A radiação ionizante é um importante fator de risco para a formação de RET/PTC, no entanto, o mecanismo molecular responsável por essa translocação radioinduzida ainda não foi elucidado. Nos últimos anos, nosso grupo demonstrou um papel crítico exercido pelas espécies reativas de oxigênio na formação de RET/PTC em células tireoidianas in vitro e também mostrou que a irradiação promove um estresse oxidativo persistente causado pelo aumento de expressão da NADPH Oxidase DUOX1, levando à dano ao DNA, mediando assim parte dos efeitos da radiação. No entanto, como o ROS leva à formação de RET/PTC ainda não é compreendido. Crianças possuem um risco significativamente mais alto de desenvolver tumores tireodianos após a irradiação, especialmente RET/PTC positivos, provavelmente em função da intensa proliferação das células tireodianas. Essa associação sugere que a replicação esteja envolvida na formação de RET/PTC. De fato, foi observado que a indução farmacológica de estresse replicativo pode estimular a formação in vitro de RET/PTC em células tireodianas. Portanto, para investigar se o estresse replicativo contribui com os efeitos da irradiação no longo prazo sobre o dano ao DNA e formação de RET/PTC, nós investigamos o papel da radiação sobre o estresse oxidativo e replicativo, além da dinâmica de replicação de linhagem de células tireodianas NTHY-ori 3.1. Nossos resultados confirmam que a irradiação desencadeia duas ondas de estresse oxidativo: primeiramente, um forte, mas transitório pico de espécies reativas de oxigênio é observado minutos após a irradiação, seguido por um novo e persistente pico que só é observado a partir de dois dias após a irradiação. Esses dois picos de estresse oxidativo resultam em dois picos de dano ao DNA. A irradiação causou pouco ou nenhum efeito na proliferação ou na progressão do ciclo celular. No entanto, vários marcadores de estresse replicativo foram observados três dias após a irradiação, como pATR, pATM, pChk1 e pRPA. Além disso, a análise da dinâmica de replicação mostrou uma diminuição na velocidade da replicação que foi revertida por antioxidantes, sugerindo que o estresse oxidativo contribui para distúrbios dos mecanismos replicativos. Por fim, utilizando ChIP-qPCR, nós observamos que os genes envolvidos na translocação RET/PTC possuem mais quebras duplas do que genes endógenos, dias após a irradiação. Portanto, propomos que o estresse replicativo está potencialmente envolvido na etiologia dos tumores RET/PTC positivos.

Das Nutzen von 3D-Anmerkungselementen unter PTC Creo-Parametric ermöglicht die Erstellung von 3D-CAD-Modellen mit ausführlichen Informationen zu Funktion, Tolerierung und Fertigung. Dadurch kann der Archivierungs- und Versionspflegeaufwand von Produktdaten und ein besseres, räumliches Verständnis für das Produkt in seiner Entstehungsphase erreicht werden.