Le cancer colorectal représente la troisième forme de cancer la plus fréquente au Canada. Malgré les récents développements, aucun traitement curatif n’est disponible pour les patients diagnostiqués à un stade avancé de la maladie. Plusieurs évidences supportent un rôle important des prostaglandines dans cette maladie. En effet, une surexpression des récepteurs de type EP et FP est remarquée. Ces derniers ainsi que les molécules de signalisations intracellulaires qu’ils activent représentent donc de nouvelles cibles pour traiter ce cancer. Nous et d’autres groupes avons démontré que les protéines G monomériques sont des petits interrupteurs moléculaires importants dans la signalisation intracellulaire engagée par les récepteurs dans des cellules saines mais qu’un dérèglement de celles-ci est associé au cancer. L’objectif principal de ce projet de recherche vise donc à identifier les voies de signalisations par lesquelles le récepteur FP contribue aux capacités invasives des cellules tumorales d’origine colorectale. Notre hypothèse est que la protéine ARF6, une des 6 isoformes des ARFs, et la protéine RhoA, agissent pour coordonner l’activation des voies de signalisations associées à la migration et l’invasion cellulaire. Nos résultats ont indiqué que la stimulation des cellules HEK293 exprimant de façon stable le récepteur FP (HA-FP) ainsi que les cellules SW480, une lignée invasive de cancer colorectal, par le PGF2α augmentait les niveaux d’activation d’ARF6 mais également de la protéine RhoA. De plus, d’autres médiateurs et intermédiaires associés à la réorganisation du cytosquelette comme la cofiline et la chaine légère de la myosine (MLC) ont été hautement phosphorylés suite à la stimulation par la prostaglandine. Ces observations sont associées avec une augmentation des fibres de stress dans les cellules. Nous avons tenté de déterminer si l’inhibition de ces protéines G affectait la capacité du PGF2α à activer ces intermédiaires de signalisation ainsi que certains effets biologiques. Ainsi, nos expériences contribueront à identifier de nouvelles cibles thérapeutiques potentielles pour le traitement du cancer colorectal. / Colorectal cancer is the third most common form of cancer in Canada. Despite recent developments, no curative treatment is available for patients diagnosed at an advanced stage of the disease. Several evidences support an important role of prostaglandins in this disease. Indeed, overexpression of EP-like and FP receptors is noticed. These and intracellular signaling molecules that are activated following receptor stimulation, represent new targets for treating cancer. We and others have demonstrated that monomeric G proteins are important molecular switches coordinating intracellular signaling cascades initiated by receptors in normal cells but that disruption thereof is associated with cancer. The main objective of this research project aims to identify the signaling pathways by which the FP receptor contributes to the invasive capacity of tumor cells of colorectal origin. Our hypothesis is that the proteins ARF6, one of the 6 ARF isoforms, and RhoA protein, act to coordinate the activation of signaling pathways associated with cell migration and invasion. Our results show that stimulation of HEK293 cells that stably express the FP receptor (HA-FP) and SW480 cells, a lineage of invasive colorectal cancer that endogenously express FP receptor, by PGF2α, increased the level of activation of ARF6, but also that of RhoA. In addition, other mediators and intermediates associated with cytoskeleton reorganization such as cofilin and the myosin light chain (MLC) were found highly phosphorylated following stimulation by prostaglandin PGF2α. These observations are associated with an increase of stress fibers in cells. Finally, we have examinated whether inhibition of ARF6 and RhoA, affected the ability of PGF2α to activate these effectors and some biological effects. Thus, our results will contribute to identify new potential therapeutic targets for the treatment of colorectal cancer.

L’hémostase primaire est un processus permettant la formation d’un clou plaquettaire qui sera stabilisé par un réseau de fibrine. Ce caillot est également consolidé grâce à des phases tardives de l’hémostase primaire résultant des fonctions plaquettaires ; il s’agit principalement de la rétraction qui diminue la taille du caillot afin de le stabiliser. Cette phase est déclenchée par une signalisation « outside-in », consécutive à l’activation de l’intégrine αIIbβ3 et à l’agrégation plaquettaire, et est dépendante d’une réorganisation du cytosquelette. Le premier objectif de ce travail a été d’étudier la signalisation impliquée dans la rétraction, et en particulier l’implication des protéines ROCK, MLCK, Rac-1 et de l’actine dans l’activité de la chaine légère de la myosine (MLC) . MLC est en effet une protéine clé de la réorganisation du cytosquelette. Nous avons mis en évidence une phosphorylation biphasique de MLC dont le deuxième pic, corrélé à la rétraction, est dépendant de Rac1 et de la polymérisation de l’actine. Cette étude a été appliquée à une pathologie, le syndrome de Lowe. Il s’agit d’une maladie génétique rare, également appelée OCRL (Oculo cérébro rénal de Lowe) en référence aux organes majoritairement touchés. Suite à l’observation d’événements hémorragiques per et postopératoires suggérant une instabilité du caillot et l’observation dans une étude précédente d’un temps d’occlusion allongé au PFA100®, nous avons mis en place une étude sur 15 patients et 15 témoins pour lesquels nous avons étudié les différentes phases de l’hémostase primaire. Outre une anomalie et un retard de maturation des mégacaryocytes, nous avons mis en évidence pour la première fois chez ces patients un défaut de la voie « outside-in » responsable d’une anomalie de l’étalement plaquettaire et de la rétraction du caillot. Ce défaut de rétraction, dû à un défaut d’activation de MLC, pourrait être en partie responsable des événements hémorragiques observés chez ces patients. / Primary hemostasis is a mechanism allowing platelet clot formation that is thereafter stabilized by a fibrin network. Fibrin clot is also consolidated following post occupancy events, mainly clot retraction that decrease clot size and thus strengthen it. This phase is triggered by « outside-in » signaling. It is consecutive to αIIbβ3 integrin activation and platelet aggregation, dependent on cytoskeleton organization. Our first objective was to investigate signaling events underlying retraction, and particularly the involvement of ROCK, MLCK, Rac-1, and actin in MLC (Myosin Light Chain) phosphorylation. Indeed, MLC, involved in cytoskeleton rearrangement, is a key protein of this mechanism. We described a MLC biphasic phosphorylation profile, which second peak was dependent of Rac1 and actin polymerization. In a second part, we studied clot retraction signaling in patients with the Lowe syndrome. It is a rare genetic disease, caused by absence of OCRL (oculo cerebro renal of Lowe) protein in reference to the majority of affected organs. The rationale of this study was a previous observation of hemorrhagic events during and after surgeries, suggesting clot instability. A thrombopathy was suggested by a closure time lengthening in the PFA-100 system. The study enrolled 15 patients and 15 controls. Besides a defect of megakaryocyte maturation, we described a defect of « outside-in » signaling responsible for spreading and clot retraction abnormality. This retraction defect, caused by a MLC activity defect, could be partly responsible for hemorrhagic events reported in these patients.

Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...

Made available in DSpace on 2016-12-12T20:12:29Z (GMT). No. of bitstreams: 1 PGEF14MA018.pdf: 2251475 bytes, checksum: 4100f5ef3f222de175d6c1fdf9eb1671 (MD5) Previous issue date: 2014-07-28 / Structural elements in glued laminated timber (GLT) are made mostly with exotic wood from planted forests. However, no studies to evaluate the economic performance of native forest species planted in Brazil for use in GLT. This study aimed to evaluate the economic and environmental viability of native species planted forest, Paricá (Schizolobium amazonicum) for the design of structural parts in GLT. For this, we used a tool called, Business Plan to analyze the production and market for GLT Paricá chain as well as in the manufacture of laboratory GLT beams with this species to determine the coefficients of production cost and sustainability indexes. Based on these studies it was found that the result shows great potential economic profitability, low cost and potential market growth. And the environmental scenario, this product is characterized as sustainable, obtaining the LEED Reference and House, and other seals being possible. In this sense, it is concluded that the beam GLT Paricá product has great market potential for being an innovative and strong environmental appeal producer, thus meeting the demand for products and solutions in the construction of the Brazil market that meet environmental requirements / Elementos estruturais em Madeira Laminada Colada (MLC) são constituídos, em sua maioria, com madeiras exóticas de florestas plantadas. Entretanto, não existem pesquisas que avaliem o desempenho econômico de espécies nativas de floresta plantada no Brasil para uso em MLC. Este trabalho teve como objetivo avaliar a viabilidade econômica e ambiental da espécie nativa de floresta plantada, o Paricá (Schizolobium amazonicum) para a concepção de peças estruturais em MLC. Para tanto, foi empregado, uma ferramenta denominada, Plano de Negócios para a análise da cadeia de produção e mercado para o MLC de Paricá, bem como a confecção em laboratório de vigas MLC com esta espécie para a determinação dos coeficientes de custo de produção e índices de sustentabilidade. Com base nestes estudos verificou-se que o resultado econômico demonstra grande potencial de lucratividade, custos baixos, mercado potencial e em crescimento. E no cenário ambiental, este produto caracteriza-se como sustentável, sendo possível a obtenção dos selo LEED e Referencial Casa, e demais selos. Neste sentido, conclui-se que o produto viga MLC de Paricá tem grande potencial de mercado por ser um produtor inovador e forte apelo ambiental, atendendo desta forma a demanda por produtos e soluções no mercado da construção civil do Brasil que cumpram exigências ambientais

Den 8:e januari 2005 inträffade en av de mest förödande stormarna i Sveriges historia då hundratusentals blev strömlösa och sju personer miste livet. Stormen Gudrun drabbade centrala Götaland värst och uppemot nio årsavverkningar skog beräknas ha fällts i vissa områden. Tidigare studier av stormen har genomförts på uppdrag av Skogsstyrelsen där resultaten visar att andel stormfälld skogsmarksareal var 11 % i värst drabbade Ljungby kommun, och ca 80 % av all den stormfällda skogen var gran, 18 % var tall och 2 % var löv. Syftet med arbetet är att undersöka mängden stormfälld skog efter stormen Gudrun genom analys av satellitburen fjärranalysdata. Även andelen stormfälld barr- och lövskog beräknades och resultaten jämfördes med de rapporter skrivna för Skogsstyrelsen. Även andelen stormfälld skog som är återbeskogad år 2016 beräknades. En förändringsanalys med satellitbilder från Landsat 5, tagna åren 2004 och 2005, genomfördes vilken inkluderade en skogsmask som skapades genom övervakad MLC-klassificering. Skogsmasken användes för att utesluta ointressanta områden i analyserna. Resultatet användes sedan för analys av andelen stormfälld barr- och lövskog samt för analys av återbeskogade områden år 2016. I den sistnämnda skapades en skogsmask med en satellitbild från Landsat 8 och som sedan användes i analysen. Resultaten från analyserna visar att ca 15,8 % av skogen stormfälldes, varav 78 % var barrskog och 13 % var lövskog. År 2016 hade ca 25 % av de stormfällda områdena återbeskogats. Noggrannheten på resultaten är generellt höga men skiljer sig trots detta väsentligt från resultaten i studierna som gjorts för Skogsstyrelsen. Anledningen till att resultaten skiljer sig åt kan bero på vilka satellitbilder och program som använts i analyserna, samt felkällor som uppkommit i samband med analyserna i denna studie. / On January 8th, 2005 one of the most devastating storms in Sweden’s history occurred, where hundreds of thousands became powerless and seven people lost their lives. The storm Gudrun hit central Götaland worst and nearly nine years’ professional felling of forests was estimated to have fallen in some areas. Previous studies of the storm were carried out on behalf of the Swedish Forest Agency, where the results show that the proportion of windthrown forest area was 11 % in the worst affected municipality of Ljungby. About 80 % of all damaged forests were spruce, 18 % were pine and 2 % were deciduous.                        The aim of this thesis is to investigate the amount of windthrown forest after the storm Gudrun through analysis of satellite remote sensing data. The proportion of windthrown coniferous and deciduous forest was calculated and the results were compared to the reports written on behalf of the Swedish Forest Agency. Furthermore, the proportion of reforested areas in 2016 was calculated. A change analysis based on satellite data from Landsat 5 from 2004 and 2005 was performed which included a forest mask created by supervised MLC classification. The forest mask was used to exclude uninteresting areas in the analyses. The result was then used for the analysis of the proportion of windthrown coniferous and deciduous forest and for the analysis of reforested areas in 2016. In the latter, a forest mask based on Landsat 8 data was used. The results from the analyses show that about 15.8 % of the forest was windthrown, of which 78 % were coniferous and 13 % were deciduous forest. By 2016, 25% of the windthrown areas had been reforested. The accuracy of the results is generally high, but despite this, it substantially differs from the results of earlier studies. The reason for this could be differences in satellite images and programs and additional error sources in conjunction with the analyses.

I samband med byggprojekt uppstår det berg- och jordmassor som måste hanteras. De senaste årens ökade bostadsbyggande och stora infrastrukturprojekt i kombination med en ökad miljömedvetenhet har lett till att olika effektiviseringar av massahantering hamnat i fokus. En sådan effektivisering är  en samordnad återvinning av massa centralt mellan olika byggprojekt och som enligt studier kan minska både antalet transporter och total miljöpåverkan, en sådan plats kallas för masslogistikcenter (MLC). Kostnadsstrukturen hos ett MLC är dock outforskat vilket försvårar skapandet av hållbara affärsmodeller. Med detta som motivering är studiens syfte följande: Syftet är att skapa en modell för att beräkna kostnaden av att driva ett MLC Modellbyggnadens struktur och dess viktiga komponenter belästes i en inledande litteraturstudie tillsammans med fakta om masshantering och centraliserad materialhantering. En metod för modellutförande utvecklades med tre större steg: utformande av en konceptuell modell, kvantifierande av modellen till en datamodell och slutligen ett test av modellen för att förbättra den. Litteratur om masshantering belyste det komplexa ämnet där massa beroende på omständigheter och sort kan variera från avfall till handelsvara. Slutligen belystes den teoretiska bakgrund som finns till centraliserad materialhantering med fokus på bygglogistikcenter som visar sig kunna minska kostnader vid byggprojekt. Modellen utvecklades sedan i tre större faser utifrån den valda metoden för modellutförande och modellens utveckling överensstämmer med rapportens tre huvudfrågor. I första fasen anlades en konceptuell modell med stöd av den gjorda litteraturstudien och semistrukturerade intervjuer av personer kunniga inom masshantering och erfarna av aktiviteter i och runt ett MLC. I modellbyggandets andra fas kvantifierades den konceptuella modellen. En aktivitetsbaserad kalkyl passade den konceptuella modellens utformning bäst. Den tredje fasen testade sedan modellen på framtida byggprojekt i norra Norrköping, utifrån detta experiment förbättrades modellen ytterligare. Resultatet sammanfattar aktiviteter i det studerade systemet och resurser som används av dessa aktiviteter. Det kan sammanfattas som att mängden massa, massans typ samt dess föroreningsgrad driver flera kostnader. Allra mest kostsam är den massa som sorteras ut i MLC för kvittblivning. Systemet blir alltså kostnadseffektivt om man så tidigt som möjligt i processen kan sortera ut det material som i så hög grad som möjligt kan återvinnas. Resultatet visar vidare att ett MCL:s kostnadsstruktur påverkas av dess geografiska placering som blir en vägning mellan närhet till projekt och markpris. Närhet till projekt minskar transportkostnader medan billig mark möjliggör i sin tur antingen lägre kostnad för mark eller större möjligheter till lagring som ökar återvinning och minskar deponikostnader. På detta sätt är flera större kostnadsposter också direkt beroende av MCL:s placering. Ett annan vägning mellan kostnader är när krossning ska genomföras, varje krossning innebär en startkostnad samtidigt som behövd lageryta ökar när krossningar görs mer sällan. Slutligen innebär ett MLC en viss planering av såväl transporter som lager, detta driver kostnader för administrativt arbete vars kostnad måste bäras av den minskade deponeringen och transporten som ett MLC kan möjliggöra. Kvantifieringen av modellens massflöden gjordes enligt en tolkning av en ABC-kalkyl med minsta tidsenhet en vecka. Testet av modellen, med data från Optimass, på ett antal projekt i Norrköping gav en rad förbättringar av modellen. Dessutom grundlade testet tillsammans med ett enkelt referensscenario att ca 30 % av driftkostnaderna kunde sparas med ett MLC. Genom att modellen skapats, testats och förbättras har studiens syfte uppfyllts. Denna studie är ett steg i att analysera möjligheterna med ett MLC. Vidare forskning behövs bland annat inom områdena: marknaden för återvunna massor, andra användningsområden för lera och investeringskostnader för ett MLC. / In connection with construction projects, large quantities of rock and soil are excavated and need to be handled. In recent years, increased housing construction and large infrastructure projects in combination with an increased environmental awareness has contributed to an increased interest in rock and soil management. A rock and soil consolidation centre (from now on SCC) is a location where recycling of rock and soil can be coordinated between different construction projects in the area. A centre like this can, according to studies, lower both number of transports needed and the total environmental impact. However, the cost structure of a rock and soil consolidation centre lacks research, which makes it difficult to create sustainable business models. The structure of model building and its important components, together with facts regarding rock and soil management and centralized material handling were studied with a literature study. A method for creating a model was developed using three steps: firstly, designing a conceptual model; secondly, quantifying the model into a computer model and lastly test and improve the model. Literature regarding rock and soil management highlighted the complicated matter of the different uses of rock and soil, where, on one hand, when excavated by a construction/excavation company, it is considered waste and may not be dumped haphazardly. On the other hand, if the rock and soil were collected and deposited into an SCC, it may be sold for reuse and hence becomes a commercial product. The literature also showed how in theory a centralized construction logistic can lower costs during construction projects. The model was developed in three phases, each corresponding to the three main questions of the study. The first phase focuses on the creation of a conceptual model, which was made possible with sources in the literature and the semi-structured interviews with respondents working in the rock and soil management field. The second phase moved the conceptual model into a computer model. An activity-based calculation was chosen to represent calculation regarding costs in the model, while the last phase focused on testing the model in Norrköping and finding improvements. The result presents activities within the studied system, as well as which resources were used to make these activities happen. The results can be summarized by saying that the volume of rock and soil, what types of rock and soil used and the levels of contamination are the main drivers of a higher total cost. The costliest part is connected to the fee for taking rock and soil waste to landfills. Since this cost can be reduced if a product is recycled, a lot of the cost can be lowered if rock and soil that can be reused is sorted out early. The result also shows that an SCC’s cost structure is affected by its geographical location, which becomes a balance between proximity to projects and cheaper, more accessible land further away from a city. Another crossroad is when to conduct crushing of rocks and soil, since there is a high start-up cost and at the same time more storage is needed if the crushing of rock and soil is carried out less frequently. Lastly an SCC requires some planning regarding its operations and transports which in hand also contributes to increased administrative costs, costs which all need to be lower than the option of driving the rock and soil to a landfill. To quantify the module was done according to an interpretation of an activity-based calculation with a time unit of a week. The test of the model, with data from Optimass on several development projects in Norrköping, resulted in some improvements of the model. The test also could also be compared to a simple reference scenario where approximately 30% of the total cost could be saved with an SCC. It also showed a pay-off time of around a year. By creating, testing, and improving the model the purpose of the study has been accomplished. This study is a step in analysing the possibilities with an SCC. Further research is needed to determine the market for recycled rock and soil products, other usable areas for products such as clay and more accurate calculations regarding the investment costs of an SCC.

No cenário da produção de edificações sustentáveis, a madeira laminada colada (MLC) ocupa lugar de destaque, sobretudo pela possibilidade de emprego de madeiras provenientes de florestas plantadas. Com o propósito de amenizar os problemas de durabilidade, quando exposta às intempéries, uma solução pressupõe a associação das vigas de MLC com um tabuleiro de concreto armado, sendo as partes ligadas por meio de conexões flexíveis. Essa técnica tem sido aplicada com sucesso, especialmente por conta do expressivo acréscimo de rigidez proporcionado pela composição. No entanto, em situações de elevados carregamentos ou de grandes vãos, a aplicação de reforços com fibras sintéticas, na face tracionada das vigas de MLC, aprimora ainda mais essa técnica, refletindo-se em significativos acréscimos nas forças de ruptura. Neste trabalho avaliou-se, de forma experimental e numérica, o comportamento estrutural de vigas mistas de MLC-concreto reforçadas com fibras de vidro. Numa primeira etapa foram estudados os elementos de ligação, optando-se pelos ganchos de aço com diâmetro de 8 mm pelo seu excepcional desempenho. Em seguida foram confeccionadas as vigas mistas, com e sem reforços com fibras de vidro, registrando-se acréscimo médio de 37% no módulo de ruptura (MOR) das vigas mistas em relação às vigas de MLC, ambas reforçadas com fibras. O emprego do reforço com fibras sintéticas se justifica pela diminuição na dispersão dos resultados. Por fim, um algoritmo foi proposto para o dimensionamento das vigas mistas de MLC-concreto reforçadas com fibras de vidro, o qual, associado às avaliações numéricas e experimentais, permite ampliar os horizontes de aplicação das estruturas de madeira. / Production of sustainable constructions forms a scenario where glulam beams occupy a prominence place, because of the possibility of utilization of wood that comes from planted forests. With the intention of diminution in the durability problems, when exposed to the weather effects, a solution presupposes the association of glulam beams with a reinforced concrete slab, in which the components are linked by means of flexible connections. This technique has been applied with results, especially due to the expressive increment in stiffness provided by the composition. However, in situations where high loads or great spans are found, the application of synthetic fibers reinforcements in the tension side of glulam beams improve this technique, being reflected in significant increments in the rupture forces. In this study it was evaluated, in experimental and numerical way, the structural behavior of glulam-concrete composite beams reinforced with glass fiber reinforced polymer (GFRP). In a first stage the connection elements were studied, being opted for steel hooks with 8 mm in diameter because of their exceptional behavior. Soon after, the composite beams were made with and without GFRP reinforcements and their tests showed average increment of 37% in modulus of rupture (MOR), when the composite beams were compared to glulam beams, both reinforced with GFRP. The decrease in the variability of results justifies the use of synthetic fibers reinforcements. Finally, an algorithm was proposed for the design of glulam-concrete composite beams reinforced with GFRP. So, when associated with the experimental and numerical evaluations that were carried out, this method allows enlarging the horizons of timber structures applications.

Neste trabalho é apresentada uma intercomparaçào das características dosimétricas entre três sistemas de colimadores multi-lâminas: Varian Millenium com 120 lâminas, mMLC m3 Brainlab e Varian Mark II ambos com 52 lâminas. A largura da projeção das lâminas no isocentro e na região central do campo é de 0,5 cm; 0,35 cm e 1,0 cm respectivamente. Foram comparadas características dosimétricas comuns aos três sistemas em modo estático e, no modo dinâmico, o trabalho limitou-se aos dois primeiros. Em modo dinâmico, foram realizados testes que avaliam o funcionamento através da irradiação em filme de figuras padrão, como a reprodutibilidade e estabilidade do MLC. Foi testada a linearidade das UM, sensibilidade â interrupção de tratamentos, a constância na velocidade das lâminas encontrando-se em todos os casos dentro do ±3%. Na linearidade da taxa de dose existem diferenças quando este parâmetro diminui. Encontrou-se que o desvio médio da dose é inversamente proporcional à abertura média dos campos dinâmicos. O fator de rendimento em modo dinâmico apresentou variações de até 1% quando o sistema suporte funcional se encontrava em posições laterais. Para os três sistemas de MLC, nos perfis para um mesmo tamanho de campo foi observada uma inclinação maior na região de penumbra para o mMLC; nos fatores de rendimento existem também pequenas diferenças de um sistema para outro. A abertura dosi métrica entre pares de lâminas foi determinado para o MLC 120, mMLC e MLC 52, os valores obtidos para 6 MV foram: (0,202 ± 0,054) cm; (0,157 ± 0,070) cm e (0,189 ± 0,081) cm respectivamente. A transmissão apresentou um comportamento crescente com a profundidade e o tamanho de campo para 6 MV nos três sistemas. Os valores médios determinados com câmara de ionização para 6 MV foram os seguintes: (1,630 ± 0,018)% para o MLC 120; (1,291 ± 0,029)% para o mMLC e (1,638 ± 0,010)% para o MLC 52. Quando testada com filme, a transmissão entre as lâminas e intralâminas apresentou dependência com a posição fora do eixo central tanto no MLC 120 quanto no mMLC. A porcentagem de espalhamento produzido pelo MLC, com relação a um campo aberto de referência de 6 MV foi: (0,297 ± 0,024)% para o MLC 120; (0,239 ± 0,052)% para o mMLC e (0,202 ± 0,028)% para o MLC 52. A penumbra (80-20%) em função do deslocamento fora do eixo não apresentou variações significativas nos três sistemas. Para todos os MLCs, a penumbra apresentou um comportamento crescente em função do tamanho de campo definido pelas lâminas. Em função da profundidade em 6 MV, a penumbra apresentou o menor valor para o mMLC em d max: 2,59 mm e o maior é 6,74 mm para o MLC Mark II a 10 cm de profundidade. A penumbra em função do ângulo que as lâminas formam com o seu eixo de movimento, para o ângulo de 10° no mMLC apresentou um valor 3,74 mm; já para os ângulos maiores, os maiores valores foram os obtidos para o Mark II. A série de testes descrita no presente trabalho permite estabelecer uma rotina no comissionamento de sistemas de MLC que pode ser aplicada nos serviços de Radioterapia que vão comissionar sistemas de MLC para IMRT em modo dinâmico. Os resultados descritos permitem caracterizar cada um dos sistemas de MLC estudados. Não é possível dizer que um sistema é melhor que outro, mas é possível, a partir da escolha de um deles, identificar as possíveis vantagens e desvantagens que cada um vai apresentar. / In this work a dosimetric comparison between three multileaf collimator systems is presented: a Varian Millennium with 120 leaves, Brainlab mMLC m3 and Varian Mark II both with 52 leaves. The width projection at isocenter level in field\'s central region are: 0,5 cm; 0,35 cm and 1,0 cm respectively. Common dosimetric characteristics for the three systems in static mode and dynamic capabilities for the two first were compared. In dynamic mode, tests validating proper MLC function through film irradiation were done, such MLC stability, MU linearity, treatment interruptions sensitivity, stability of MLC in dynamic mode, leaf speed stability, were found within ±3% deviation in all cases. Dose rate linearity showed differences when this parameter decreases in dynamic mode. Average dose errors for fixed width gaps moving at constant speed were found to be proportional to gap errors and inversely proportional to the gap width. Output factors differences delivered through a sweeping gap were found less than ±1% when the gantry was in a lateral position. For the three MLC systems, when comparing beam profiles for the same field was observed that for mMLC presents the sharpest dose gradient region. In the output factors small differences where observed in every MLC system. Dosimetric leaf gap was determined for MLC 120, mMLC and MLC 52, obtained values for a 6 MV beam are: (0,202 ± 0,054) cm; (0,157 ± 0,070) cm and (0,189 ± 0,081) cm respectively. The transmission showed an increase with depth and field width for 6 MV in all the three systems. Average values obtained with ionization chamber for this energy were: (1,630 ± 0,018)% for MLC 120; (1,291 ± 0,029)% for mMLC and (1,638 ± 0,010)% for MLC 52. When obtained through film irradiation, inter and intra leaf transmission showed an off axis dependent behavior for MLC 120 and mMLC. Scatter produced by MLC as a 6 MV open reference field ratio was: (0,297 ± 0,024)% for MLC 120; (0,239 ± 0,052)% for mMLC and (0,202 ± 0,028)% for MLC 52. It was verified that penumbra width (80-20%) as a function of off axis leaf position do not showed significant differences in all systems. As a function of field width defined by MLC leaves, penumbra width presented an increasing behavior. When tests as a depth function in a 6 MV field, penumbra showed the smallest value for the mMLC at dmax: 2,59 mm and the biggest was 6,74 mm for the MLC Mark II AT 10 cm depth. Penumbra dependence with leaf movement axis showed that for 10 deg, the mMLC presented a 3,74 mm value, for larger angles, the higher values were obtained for MLC Mark 11. Described series of tests described in the present investigation allows to establish a commissioning routine for MLC systems, that could be applied in a Radiotherapy Department that will commission those systems for dynamic IMRT. Obtained results allow to characterize every MLC studied system. It is not possible to establish which system is better, but when one is chosen it is feasible to identify vantages and disadvantages that everyone will present.

Neste trabalho é apresentada uma intercomparaçào das características dosimétricas entre três sistemas de colimadores multi-lâminas: Varian Millenium com 120 lâminas, mMLC m3 Brainlab e Varian Mark II ambos com 52 lâminas. A largura da projeção das lâminas no isocentro e na região central do campo é de 0,5 cm; 0,35 cm e 1,0 cm respectivamente. Foram comparadas características dosimétricas comuns aos três sistemas em modo estático e, no modo dinâmico, o trabalho limitou-se aos dois primeiros. Em modo dinâmico, foram realizados testes que avaliam o funcionamento através da irradiação em filme de figuras padrão, como a reprodutibilidade e estabilidade do MLC. Foi testada a linearidade das UM, sensibilidade â interrupção de tratamentos, a constância na velocidade das lâminas encontrando-se em todos os casos dentro do ±3%. Na linearidade da taxa de dose existem diferenças quando este parâmetro diminui. Encontrou-se que o desvio médio da dose é inversamente proporcional à abertura média dos campos dinâmicos. O fator de rendimento em modo dinâmico apresentou variações de até 1% quando o sistema suporte funcional se encontrava em posições laterais. Para os três sistemas de MLC, nos perfis para um mesmo tamanho de campo foi observada uma inclinação maior na região de penumbra para o mMLC; nos fatores de rendimento existem também pequenas diferenças de um sistema para outro. A abertura dosi métrica entre pares de lâminas foi determinado para o MLC 120, mMLC e MLC 52, os valores obtidos para 6 MV foram: (0,202 ± 0,054) cm; (0,157 ± 0,070) cm e (0,189 ± 0,081) cm respectivamente. A transmissão apresentou um comportamento crescente com a profundidade e o tamanho de campo para 6 MV nos três sistemas. Os valores médios determinados com câmara de ionização para 6 MV foram os seguintes: (1,630 ± 0,018)% para o MLC 120; (1,291 ± 0,029)% para o mMLC e (1,638 ± 0,010)% para o MLC 52. Quando testada com filme, a transmissão entre as lâminas e intralâminas apresentou dependência com a posição fora do eixo central tanto no MLC 120 quanto no mMLC. A porcentagem de espalhamento produzido pelo MLC, com relação a um campo aberto de referência de 6 MV foi: (0,297 ± 0,024)% para o MLC 120; (0,239 ± 0,052)% para o mMLC e (0,202 ± 0,028)% para o MLC 52. A penumbra (80-20%) em função do deslocamento fora do eixo não apresentou variações significativas nos três sistemas. Para todos os MLCs, a penumbra apresentou um comportamento crescente em função do tamanho de campo definido pelas lâminas. Em função da profundidade em 6 MV, a penumbra apresentou o menor valor para o mMLC em d max: 2,59 mm e o maior é 6,74 mm para o MLC Mark II a 10 cm de profundidade. A penumbra em função do ângulo que as lâminas formam com o seu eixo de movimento, para o ângulo de 10° no mMLC apresentou um valor 3,74 mm; já para os ângulos maiores, os maiores valores foram os obtidos para o Mark II. A série de testes descrita no presente trabalho permite estabelecer uma rotina no comissionamento de sistemas de MLC que pode ser aplicada nos serviços de Radioterapia que vão comissionar sistemas de MLC para IMRT em modo dinâmico. Os resultados descritos permitem caracterizar cada um dos sistemas de MLC estudados. Não é possível dizer que um sistema é melhor que outro, mas é possível, a partir da escolha de um deles, identificar as possíveis vantagens e desvantagens que cada um vai apresentar. / In this work a dosimetric comparison between three multileaf collimator systems is presented: a Varian Millennium with 120 leaves, Brainlab mMLC m3 and Varian Mark II both with 52 leaves. The width projection at isocenter level in field\'s central region are: 0,5 cm; 0,35 cm and 1,0 cm respectively. Common dosimetric characteristics for the three systems in static mode and dynamic capabilities for the two first were compared. In dynamic mode, tests validating proper MLC function through film irradiation were done, such MLC stability, MU linearity, treatment interruptions sensitivity, stability of MLC in dynamic mode, leaf speed stability, were found within ±3% deviation in all cases. Dose rate linearity showed differences when this parameter decreases in dynamic mode. Average dose errors for fixed width gaps moving at constant speed were found to be proportional to gap errors and inversely proportional to the gap width. Output factors differences delivered through a sweeping gap were found less than ±1% when the gantry was in a lateral position. For the three MLC systems, when comparing beam profiles for the same field was observed that for mMLC presents the sharpest dose gradient region. In the output factors small differences where observed in every MLC system. Dosimetric leaf gap was determined for MLC 120, mMLC and MLC 52, obtained values for a 6 MV beam are: (0,202 ± 0,054) cm; (0,157 ± 0,070) cm and (0,189 ± 0,081) cm respectively. The transmission showed an increase with depth and field width for 6 MV in all the three systems. Average values obtained with ionization chamber for this energy were: (1,630 ± 0,018)% for MLC 120; (1,291 ± 0,029)% for mMLC and (1,638 ± 0,010)% for MLC 52. When obtained through film irradiation, inter and intra leaf transmission showed an off axis dependent behavior for MLC 120 and mMLC. Scatter produced by MLC as a 6 MV open reference field ratio was: (0,297 ± 0,024)% for MLC 120; (0,239 ± 0,052)% for mMLC and (0,202 ± 0,028)% for MLC 52. It was verified that penumbra width (80-20%) as a function of off axis leaf position do not showed significant differences in all systems. As a function of field width defined by MLC leaves, penumbra width presented an increasing behavior. When tests as a depth function in a 6 MV field, penumbra showed the smallest value for the mMLC at dmax: 2,59 mm and the biggest was 6,74 mm for the MLC Mark II AT 10 cm depth. Penumbra dependence with leaf movement axis showed that for 10 deg, the mMLC presented a 3,74 mm value, for larger angles, the higher values were obtained for MLC Mark 11. Described series of tests described in the present investigation allows to establish a commissioning routine for MLC systems, that could be applied in a Radiotherapy Department that will commission those systems for dynamic IMRT. Obtained results allow to characterize every MLC studied system. It is not possible to establish which system is better, but when one is chosen it is feasible to identify vantages and disadvantages that everyone will present.

In recent years intensity modulated radiation therapy with photons (xIMRT) has gained attention due to its ability to reduce the dose in the tissues close to the tumour volume. However, this technique also results in a large low dose volume. Electron IMRT (eIMRT) has the potential to reduce the integral dose to the patient due to the dose fall off in the electron depth dose curves. This dose fall off makes it possible to modulate the dose distribution in the direction of the beam by selecting appropriate electron energies. The use of a computer based energy selection method was examined in combination with the IMRT technique to optimise the electron dose distribution. It is clearly illustrated that the energy optimisation procedure reduces the dose to lung and heart in a breast cancer treatment. To shape the multiple electron subfields (beamlets) that are used in eIMRT, an electron multi leaf collimator (eMLC) is needed. However, photons produced in a conventional electron treatment head could penetrate such an added eMLC, thus producing an undesirable dose contribution. The leakage levels normally achieved are acceptable for standard single electron field treatments but could become unacceptably high in eIMRT treatments where a lot of small subfields are combined. To limit this photon contribution, the photon MLC (xMLC) was used to shield off large parts of the photon leakage. The effect of this xMLC shielding on the reduction of photon leakage, the electron beam penumbras, and electron output (dose level), was studied using Monte Carlo methods for different electron treatment head designs. The use of helium as a mean to reduce the electron scatter in the treatment head, and thus the perturbating effect of the xMLC on electron beam penumbra and output, was also investigated. This thesis shows that the effect of the xMLC shielding on the electron beam penumbra and output can be made negligible while still obtaining a significantly reduced x-ray leakage dose contribution. The result is a large gain in radiation protection of the patient and a better dynamic range for the eIMRT dose optimisation. For this optimisation a computer based electron energy selection method was developed and tested on two clinical cases.