Industrin står idag inför skenande prishöjningar av framförallt råvaror som metall, dettaberor bland annat på Covid-pandemin men också andra oroligheter som sker omkring ivärlden. Detta sätter mer och mer press på befintliga tillverkande företag inom landetsamtidigt som pressade priser från andra länder konkurrerar. Detta skapar ett krav avinnovativt, resurssnålt och effektivt tänkande kring svenska industrier. Trots detta ståräven svenska industrier inför en stor möjlighet då fler och fler industrier vill ta tillbakasin tillverkning från utlandet.Företagen kan bli mer effektiva och skapa en förbättrad kvalité med Lean filosofin. Föratt lyckas med detta måste kortare ledtider och lägre kostnader uppnås.Sverige består till stor del av SME företag. 97% av Sveriges tillverkande företag harmindre än 50 anställda och samtidigt finns det endast cirka 100-150 företag inomtillverkning som har mer än 500 anställda. Detta medför att relevansen medimplementering av Lean och effektivisering inom SME är ett viktigt steg för en stor delav Sveriges tillverkande ekonomi.Syftet med denna studie är att undersöka om Lean kan bidra till effektiviseringar hosmindre tillverkande företag. Det har utförts en fallstudie på ett utvalt mindretillverkande företag som befinner sig i regionen. Metoder inom Lean som 5S, Kanban-system och koncept utifrån Toyota Production System (TPS) har lagts fram someventuella förbättringsförslag men även vilka svårigheter som kan uppkomma meddem. Det har utförts en fallstudie där intervjuer på företaget gjort samt en litteraturstudiehar genomförts inom de relevanta områdena. Utifrån den analys som genomförts understudiens har förbättringsförslag kunnat framställas om vad som kan hjälpa fallföretagetvid en potentiell implementering.Resultatet av denna studie är att Lean kan bidra till effektiviseringar hos mindretillverkande företag. Detta är möjligt genom mindre resursslöseri och kortare ledtider.Det krävs dock att Lean implementeras på rätt sätt och att företaget har viss kunskap.Mindre företag har ofta mindre resurser vilket kan försvåra processen, samtidigt harmindre företag ofta en högre flexibilitet vilket hjälper vid en förändring. Vidare studierav framförallt SME-företag behövs för att se om det finns likheter bland andra företagoch om detta kan vara applicerbart på SME-företag med annan inriktning och situation.

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Recent advances in plant genetic engineering offer substantial benefits to farmers throughout the world. Genetic research has identified many exogenous genes that could considerably decrease production costs through transgene-mediated resistance to insect, viral, fungal and bacterial pathogens. Potato can be produced from true potato seed (TPS) through a sexual polyploidization step, known as 4x-2x hybridization. Little is known regarding the stability of transgenes through sexual polyploidization in potato, although studies have associated ploidy elevation with transgene silencing in plants such as Arabidopsis thaliana. In the present study, potato was transformed with two different transgenes, cry3Aa and PVYo cp, and transgene expression was analyzed through 4x-2x hybridization. Transgene introgression did not affect fertility or agronomic performance (tuber set, average tuber weight, total tuber yield) of the resulting 4x-2x hybrids; however, reduced seed germination was observed for several transgenic lines in an in vitro study. Ploidy elevation did not affect a highly expressed single copy cry3Aa transgene, simplex or duplex, transmitted through pollen to 4x-2x hybrids. By contrast, multiple copies of cry3Aa triggered significant transgene silencing in diploids and silencing was further pronounced upon pollen transmission to 4x-2x hybrids. Crosses between two, single insert plants demonstrated additional evidence that multiple cry3Aa transgenes resulted in reduced expression, as well as provided evidence for maternal effects on expression of the cry3Aa transgene. Finally, Cry3Aa expression levels of progeny derived from low expressing, multiple copy 4x-2x hybrids indicated that reduction of transgene number in progeny, through meiotic segregation, could increase Cry3Aa expression. The results suggest that 4x-2x hybridization using single copy, male parents can result in high expressing, transgenic 4x-2x hybrids while segregating for a low frequency of non-transgenic hybrids that create a "refuge" to inhibit development of resistance to transgenes in pest populations. / Ph. D.

Submitted by admin tede (tede@pucgoias.edu.br) on 2017-09-18T12:35:17Z No. of bitstreams: 1 Zenilda Alexandria Taniguti.pdf: 3106241 bytes, checksum: c8b3d06c0e021fe28207a0b199bd6c37 (MD5) / Made available in DSpace on 2017-09-18T12:35:17Z (GMT). No. of bitstreams: 1 Zenilda Alexandria Taniguti.pdf: 3106241 bytes, checksum: c8b3d06c0e021fe28207a0b199bd6c37 (MD5) Previous issue date: 2017-06-08 / This research aims to elaborate directives influenced by the principles of management of the Toyota Production System (TPS) for the design of the industrial architecture project. The purpose is to contribute with the elaboration of the factory architecture project using orientations based on the positive results of TPS. The methodological approach chosen for the development of this dissertation was the Design Science Research Methodology (DSRM), directed to technological research. The research explains that the production management is based on principles that need a correct organization of the space, study and methodologies in the design of the architecture projects of the factory buildings. In addition, the work considers the possibility of the designed physical space to contribute with solutions to the organizational demands and to facilitate the application of the productive system. The research is focused in the relations between the guiding principles of the TPS and the complexities of the factory projects. With the application of DSRM, at first a theoretical review on the factory building and the most relevant principles of the TPS is carried out. Then an analysis of the relationship of the two concepts from a conceptual map establishes the design and development of a proposed Toyota Architecture Directive (DAFT). In a third moment, this set of directives is submitted to the eyes of eight experts working in the area of architecture and industry, through semistructured interviews. This evaluation allows the refinement of the set of 14 directives (DAFT) for final presentation. In the discussion of the directives by the experts interviewed the opinions link the production management with the need to study the factory space as a whole, in an interactive way. At all times, it is evident that the complexity of projects and manufacturing facilities requires specific study methodologies to solve organizational problems. As a result of the research, we also obtained evidence that the directives from the TPS tools, for the most part, can be applied in several industrial projects, considering that some experts work with other systems and considered them relevant. In this way, the DAFT can represent to the organizational challenges a possible discussion proposal to assist in the decision making in all stages of the design of the industrial architecture project. / Esta pesquisa tem como objetivo elaborar diretivas influenciadas pelos princípios de gestão do Sistema Toyota de Produção (TPS) para a concepção do projeto de arquitetura fabril. O propósito é contribuir na elaboração do projeto de arquitetura fabril com orientações baseadas nos resultados positivos do TPS. A abordagem metodológica escolhida para o desenvolvimento deste trabalho foi a Design Science Research Methodology (DSRM), direcionada para pesquisas tecnológicas. A pesquisa explicita que a gestão da produção é baseada em princípios que necessitam de uma correta organização do espaço, do estudo e de metodologias na concepção dos projetos de arquitetura dos edifícios fabris. Além disso, o trabalho considera a possibilidade do espaço físico projetado em contribuir com soluções para as demandas organizacionais e facilitar a aplicação do sistema produtivo. A pesquisa é subsidiada nas relações dos princípios norteadores do TPS e nas complexidades dos projetos fabris. Com a aplicação da DSRM, primeiro é realizada uma revisão teórica sobre o edifício fabril e os mais relevantes princípios do TPS. Em seguida, uma análise da relação dos dois conceitos a partir de um mapa conceitual estabelece o design e o desenvolvimento de uma proposta de Diretivas de Arquitetura fabril Toyota (DAFT). Em um terceiro momento, este conjunto de diretivas é submetido ao olhar de oito experts atuantes na área da arquitetura e industrial, por meio de entrevistas semiestruturadas. Esta avaliação, em um quarto momento, permite o refinamento do conjunto de 14 diretivas (DAFT) para apresentação final. Na discussão das diretivas pelos experts entrevistados, as opiniões fazem a ligação da gestão da produção com a necessidade do estudo do espaço fabril como um todo, de forma interativa. Em todos os momentos fica evidenciado que a complexidade dos projetos e das instalações fabris exige metodologias de estudo específicas para solucionar os problemas organizacionais. Como resultados da pesquisa também foram obtidas evidências de que as diretivas advindas das ferramentas do TPS, em sua maioria, podem ser aplicadas em projetos industriais diversos, considerando que alguns experts trabalham com outros sistemas e as consideraram pertinentes. Desta forma, as DAFT podem representar aos desafios organizacionais uma possível proposta de discussão para auxiliar na tomada de decisões em todas etapas da concepção do projeto de arquitetura fabril.

Pseudomonas aeruginosa est un pathogène opportuniste responsable du développement de maladies nosocomiales. Il provoque des infections en employant différents facteurs de virulence dont le principal, associé aux infections sévères, est le système de sécrétion de type 3 (SST3). Les souches de type PA7, taxonomiquement marginales, sont dépourvues de SST3 et leur pouvoir pathogène repose sur le nouveau système de virulence ExlBA. Ce SST5b, ou TPS, est composé du transporteur ExlB qui permet la translocation d’ExlA, une toxine induisant la perméabilisation de la membrane plasmique des cellules eucaryotes.Ce travail représente la première investigation des mécanismes de régulation du système ExlBA. Ainsi, il a été mis en évidence que la déplétion en fer est un signal d’activation de l’expression des gènes exlBA. De plus, les deux principaux messagers secondaires, AMPc et di-GMPc, sont impliqués dans la régulation du TPS. En effet, la voie CyaB-AMPc/Vfr, connue pour réguler le SST3, contrôle la toxicité des souches de type PA7 grâce à une activation transcriptionnelle directe des gènes exlBA, qui peut être stimulée par la chélation du calcium extracellulaire. Parallèlement, alors qu’ExlA était supposée être sécrétée pour agir sur les cellules eucaryotes, cette étude a montré que la toxine doit être exposée à la surface de la membrane bactérienne pour provoquer la lyse de ces cellules, ceci par un mécanisme dépendant du di-GMPc. Effectivement, une forte concentration en di-GMPc empêche la sécrétion d’ExlA en induisant de façon post-traductionnelle son maintien au niveau du transporteur ExlB, ce qui favoriserait l’action de la toxine sur les membranes eucaryotes. / Pseudomonas aeruginosa is an opportunistic pathogen responsible for nosocomial diseases. It provokes infections due to several virulence factors. Among them the most aggressive is the type 3 secretion system (T3SS), associated with severe infection. PA7-like strains, that are taxonomic outliers, lack the T3SS but are still pathogenic thanks to the novel virulence system ExlBA. This T5bSS, or TPS, is composed by the transporter ExlB that allows translocation of ExlA toxin to induce permeabilisation of eukaryotic cell membrane.This study is the first investigation of regulatory mechanisms that modulate ExlBA. It provided evidence that iron depletion is an activator signal of exlBA gene expression. Furthermore, the two main second messengers, cAMP and c-di-GMP, are involved in ExlBA regulation. CyaB-cAMP/Vfr pathway, known to regulate T3SS, controls toxicity of PA7-like strains through direct transcriptional activation of exlBA. This pathway may be stimulated by an extracellular calcium chelation. At the same time, while ExlA was supposed to be secreted to kill eukaryotic cells, this work showed that the toxin must be exposed at the surface of the bacterial membrane to cause lysis of these cells, by a mechanism dependent on c-di-GMP. Indeed, a c-di-GMP high concentration prevents ExlA secretion by inducing its maintenance at the ExlB transporter, that would promote the action of the toxin on eukaryotic membranes.

Lean production is the name given to Toyota’s Production System (TPS) by the west. The continuous improvements of their operations through Lean has made Toyota into the largest car manufacturer in the world. This, in turn, has led to several studies regarding both Toyota and their system as to find ways to apply Lean in other organizations. Even so, over 90 percent of all companies fail to implement Lean. Thus it becomes increasingly interesting to research as to how Lean, successfully, should be implemented.   The purpose of this thesis is to construct a model which will aid companies with the implementation process and to further the rate of success. Factors regarding what makes for a successful as well as a failed implementation will be analyzed.    A case study is used with two different companies in order to analyze empirical data in comparison to earlier research. One company represents a more successful case and the other a less successful one.    The main findings of this paper is the order of which different aspects of Lean is to be implemented to increase the possibilities for successful implementation. Furthermore the emphasis on a, for Lean, correct leadership within the company that requires genuine understanding and commitment.   The conclusion is displayed as a model where one can see the crucial steps in order to increase the success rate regarding the implementation of Lean. The main points of the model is the importance of support from leaders in combination with an accepting culture where people are of significant importance. The model can be viewed in chapter 6. / Lean är västvärldens benämning på Toyotas Produktions System (TPS). Genom att kontinuerligt förbättra sina arbetssätt har Lean gjort Toyota till världens största biltillverkare. Något som lett till att flertalet studier gjorts beträffande Toyota och deras system för att kunna applicera den framgångsrika metoden i andra verksamheter. Dock så misslyckas över 90 procent av alla företag med att implementera Lean i sina organisationer. Således blir det intressant att titta närmare på hur Lean bör implementeras för att erhålla ett lyckat resultat.   Syftet med arbetet är att utforma en modell som avser att förbättra möjligheterna för företag att framgångsrikt implementera Lean i sin verksamhet. Olika faktorer beträffande vad som utgör en framgångsrik respektive misslyckad implementering analyseras i arbetet.   En fallstudie, med två företag, används för att analysera empiriska data i förhållande till tidigare forskning. Ett av företagen representerar en mer framgångsrik implementering medan det andra en mindre framgångsrik sådan.   En av de viktigaste upptäckterna i arbetet är ordningen i vilka olika aspekter av Lean bör implementeras för att öka möjligheten för framgångsrik implementering. Vidare betonas även det ledarskap som krävs för Lean där förståelse och engagemang är viktiga aspekter.   Slutsatsen presenteras som en modell som, i enlighet med syftet, visar på nödvändiga steg vid implementering för att öka chanserna till att denna blir framgångsrik. Modellen bygger på vikten av stöd från ledare i kombination med en accepterande kultur där människor är en central del av verksamheten. Modellen visas i kapitel 6.

This study has been conducted at Scania Engine Assembly, in particular in an production area that produces Marine Engines. Scania always strives for continuous improvement and the purpose of this study has been to create an overview of the production area Marine-completion, where the marine components are assembled. The goals were to create a current state analysis, propose a future state analysis and propose suggestions of solutions for improvement of Marine-completion. The research question was: How can the strategies for the current state analysis be chosen, used and analyzed in order to accomplish a successful current state analysis?. The research methodology in this study was conducted using qualitative and quantitative research strategies, where both primary and secondary data were collected. The theoretical framework was divided into four subsections: Production systems, project management, technical solutions of today and supporting literature for solutions. The main method of this study was collecting data. The data included layout of the production, assembly times, quality deviations, engine variant classifications, Value Stream Mapping, Safety, Health and Environment related deviations and costs. Based on the current state, a future state was developed. The results of the current state analysis was that there are a total of 20 main variants of marine engines which have different assembly times. The assembly time can vary from approximately 45 minutes to 3 hours and 35 minutes for straight engines and approximately 4 hours to 8 hours for V8 engines. The mean results from Value Stream Mapping concluded a distribution of 40 percentage Value Adding and 60 percentage Non-Value Adding, where the largest waste from Non-Value Adding activities was bringing parts. Most of the quality deviations were caused by the method, where the biggest problem was regarding "tool insufficiency". Safety, Health and Environment related deviations were identified, where the largest problems were "risk". The future state analysis ended up in three cases, which explains the possible savings and future states. The Failure Mode and Effects Analysis resulted in 7 failure modes, where "Engine-card missing tasks/parts" had the largest rating. The suggestion of solutions resulted in a new layout, new routines with the engine-cards with digital screens and some other smaller suggestions. This study concluded in three main suggestions of solutions about "Newlayout at Marine-completion ", "Digital screens at each station" and "Continuous update of enginecards", which resulted in three assignment directives that Scania can further work with in the future. / Detta arbete har utförts på ett produktionsområde i Scanias motormontering i Södertälje, Stockholm. Scania strävar alltid mot ständiga förbättringar och detta arbete uppfyller det genom syftet att skapa en kartläggning över produktionsområdet med fokus i förbättringar. Målen med detta arbete var att kartlägga nuläget i Marinkompletteringen samt skapa ett framtidsläge tillsammans med föreslagna förbättringsförslag. Den forskningsrelaterade frågeställningen för detta arbete var: Hur kan strategierna för nulägesanalysen väljas, användas och analyseras för att uppnå en lyckad nulägesanalys? Metoden för litteraturstudien som utförts för detta arbete använde kvalititativa och kvantitiva forskningsmetoder där både primär och sekundärdata samlades. Det teoretiska ramverket var uppdelat i fyra delkapitel: Produktionssystem, projektledning, tekniska lösningar idag och stödjande litteratur för lösningar. Huvudmetoden för detta arbete var datainsamlingen som inkluderade aspekter som layout på området, monteringstider, kvalitetsavvikelser, motorvarianternas klassificering, värdeflödesanalys, avvikelser kopplat till säkerhet, hälsa, miljö och kostnader. Utifrån nulägesanalysen utvecklades framtidsläget fram. Resultaten från nulägesanalysen påvisade en total mängd av 20 olika huvudvarianter på marinmotorerna som monteras i marinkompletteringen med olika monteringstider. Monteringstiderna kunde sträcka sig mellan 45 minuter till tre timmar och 35 minuter för raka motorer och ungefär fyra till åtta timmar när det gäller V8 motorer. Medelvärdet på resultatet av värdeflödesanalysen resulterade i en fördelning av 40 procent värdeskapande tid och 60 procent icke-värdeskapande tid där det största slöseriet tillkom vid upphämtning av artikel. De flesta kvalitetsbristerna orsakades av metodiska fel där det mest förekommande metodiska felet var framkomlighet för verktyg. Bristerna kring säkerhet, hälsa och miljö identifierades och den mest förekommande bristen var gällande risker på arbetsplatsen. Analysen av framtidsläget resulterade i tre scenarion som vardera förklarar möjliga kostnadsbesparingar vid utfasning av olika icke-värdeskapande aktiviteter. Failure Mode and Effects Analysis som utfördes resulterade i sju feltyper varav "brist på information i motorkort" hade högst risktal. Rekommenderade åtgärder för Failure Mode and Effects Analysis resulterade i förslag om ny layout, nya rutiner gällande motorkort med digitala lösningar samt ett flertal mindre lösningar. De föreslagna lösningar som gavs till Scania i detta arbete var tre konkreta huvudförslag angående "ny layout på marinkompletteringen", "digitala skärmar på vardera station" och "kontinuerlig uppdatering av motorkort" vilket i sin tur resulterade i tre uppdragsdirektiv som Scania fortsatt kan jobba med i framtiden.

Embalagens de plástico expandido são utilizados como embalagens de alimentos, entre eles o poliestireno expandido (EPS). Suas principais características são a leveza e sua não biodegradabilidade. Estas embalagens geralmente são descartadas logo após o uso e geram grandes quantidades de resíduos. Espumas feitas a base de amido termoplástico (TPS) podem substituir o EPS nestes casos, pois são feitas a partir de fontes renováveis e são materiais biodegradáveis. Entretanto, embalagens de espuma TPS possuem grande afinidade pela água e isso consequentemente afeta seu uso. Uma forma de resolver este problema é recobrir estas espumas TPS com um material mais hidrofóbico, dificultando o contato da água com o amido. Nesse sentido, o objetivo deste trabalho foi desenvolver espumas de TPS de diferentes amidos e revesti-las com quitosana e poliácido láctico (PLA), pois também são materiais biodegradáveis e são menos hidrofílicos do que o amido. Três fontes de amido (batata, mandioca e milho) foram analisadas conjuntamente para produzir espumas TPS com propriedades mais desejáveis para embalagens. As espumas foram produzidas a partir de amido, glicerol e água nas proporções mássicas de 62/5/33, respectivamente. Dentre os tipos de amido escolhidos, a espuma TPS de milho mostrou ser mais densa e rígida, apresentando maior densidade e maior módulo elástico (0,20 g/cm3 e 106 MPa, respectivamente) em comparação com espumas TPS de batata (0,11 g/cm3 e 39 MPa) e mandioca (0,10 g/cm3 e 39 MPa). A espuma TPS de batata apresentou maior flexibilidade e resistência ao impacto, e devido a estas vantagens é a mais adequada ao uso em embalagens. Os recobrimentos de quitosana e PLA diminuíram a absorção de água da espuma TPS. Enquanto que a espuma sem recobrimento absorveu aproximadamente 280% do seu peso em água, espumas TPS com 6% m/v de quitosana absorveram 100% e espumas TPS com 6% m/v de PLA absorveram 50% em média. O PLA mostrou ser a melhor opção de recobrimento para as espumas pois apresentou os menores valores de absorção de água e aumentou as propriedades mecânicas da espuma. / The expanded polystyrene (EPS) is used in a variety of food packaging, mainly in packages whose characteristics is the single use. These packages are usually discarded soon and generate large amounts of waste. Thermoplastic starch (TPS) foams can replace the EPS in these cases, because it comes from renewable and biodegradable sources. However, starch packaging has great affinity for water and it affects its use. One way to solve this problem is to cover the TPS foam with a more hydrophobic material, hindering the contact of water with starch. In this work, chitosan and polylactic acid (PLA) were used as coatings, as they are also biodegradable materials and are more hydrophobic than starch. Three sources of starch (potato, cassava and corn) were analyzed conjointly to produce TPS foams with more desirable properties for packaging. The foams were made from starch, glycerol and water in the proportion of 62/5/33 (% m/m) respectively. Among the starch types used, corn TPS foam presented higher density and higher stiffness (0,20 g/cm3 and 106 MPa, respectively) compared to potato (0,11 g/cm3 and 39 MPa) and cassava (0,10 g/cm3 e 39 MPa) TPS foams. The potato TPS foam showed greater flexibility and impact resistance, and due to these advantages is the most suitable for use in packaging. The chitosan and PLA coatings decreased the water absorption of the TPS foam. While the uncoated TPS foam absorbed approximately 280% of its weight in water, TPS foams with 6% w/v chitosan absorbed 100% and TPS foams with 6% m / v PLA absorbed 50% on average. The PLA was found to be the best option for coating the TPS foams because presented the lowest water absorption values and increased the mechanical properties of the foams.

Cette thèse s'inscrit dans la perspective des traitements de radiothérapie en insistant sur la nécessité de disposer d’un logiciel de planification de traitement (TPS) rapide et fiable. Le TPS est composé d'un algorithme de calcul de dose et d’une méthode d’optimisation. L'objectif est de planifier le traitement afin de délivrer la dose à la tumeur tout en sauvegardant les tissus sains et sensibles environnant. La planification des traitements consiste à déterminer les paramètres d’irradiation les mieux adaptés au patient. Dans le cadre de cette thèse, les paramètres d'un traitement par RCMI (Radiothérapie Conformationnelle avec Modulation d'Intensité) sont la position de la source, les orientations des faisceaux et, pour chaque faisceau composé de faisceaux élémentaires, la fluence de ces derniers. La fonction objectif est multicritère en associant des contraintes linéaires. L’objectif de la thèse est de démontrer la faisabilité d'une méthode d'optimisation du plan de traitement fondée sur la technique de calcul de dose rapide développée par (Blanpain, 2009). Cette technique s’appuie sur un fantôme segmenté en mailles homogènes. Le calcul de dose s’effectue en deux étapes. La première étape concerne les mailles : les projections et pondérations y sont paramétrées en fonction de critères physiques et géométriques. La seconde étape concerne les voxels: la dose y est calculée en évaluant les fonctions préalablement associées à leur maille.Une reformulation de cette technique permet d’aborder le problème d’optimisation par la méthode de descente de gradient. L’optimisation en continu des paramètres du traitement devient envisageable. Les résultats obtenus dans le cadre de cette thèse ouvrent de nombreuses perspectives dans le domaine de l’optimisation des plans de traitement en radiothérapie. / This thesis deals with the radiotherapy treatments planning issue which need a fast and reliable treatment planning system (TPS). The TPS is composed of a dose calculation algorithm and an optimization method. The objective is to design a plan to deliver the dose to the tumor while preserving the surrounding healthy and sensitive tissues.The treatment planning aims to determine the best suited radiation parameters for each patient’s treatment. In this thesis, the parameters of treatment with IMRT (Intensity modulated radiation therapy) are the beam angle and the beam intensity. The objective function is multicritiria with linear constraints.The main objective of this thesis is to demonstrate the feasibility of a treatment planning optimization method based on a fast dose-calculation technique developed by (Blanpain, 2009). This technique proposes to compute the dose by segmenting the patient’s phantom into homogeneous meshes. The dose computation is divided into two steps. The first step impacts the meshes: projections and weights are set according to physical and geometrical criteria. The second step impacts the voxels: the dose is computed by evaluating the functions previously associated to their mesh.A reformulation of this technique makes possible to solve the optimization problem by the gradient descent algorithm. The main advantage of this method is that the beam angle parameters could be optimized continuously in 3 dimensions. The obtained results in this thesis offer many opportunities in the field of radiotherapy treatment planning optimization.