Analysis of the statistical methods in the company AFL Stříbro. Comparison to the VDA standard.

L'angiogénèse est un phénomène vital dans de nombreux processus physiologiques tels que le développement embryonnaire ou la cicatrisation. Mais c'est aussi un processus pathologique impliqué dans la croissance des tumeurs malignes, dans le développement des métastases et dans des maladies telles que l'endométriose, la dégénérescence Maculaire liée à l'âge (DMLA) et l'arthrose. La néovascularisation pathologique est dense et désordonnée contrairement à la néovascularisation physiologique, ce qui en fait une cible thérapeutique attrayante. Les agents perturbateurs vasculaires (VDA) sont une nouvelle classe de molécules bioactives qui détruisent sélectivement la néovascularisation tumorale et arrêtent l'apport sanguin aux tumeurs solides, provoquant une nécrose tumorale étendue. Parmi les VDA, les agents se liant à la tubuline sont principalement représentés. Le processus d'angiogénèse au sein de l'arthrose ainsi que le mode d'action des VDA nous amène a envisager l'utilisation de ses derniers en tant que nouveau traitement anti-arthrosique. Dans la recherche de nouveaux scaffolds VDA, nous avons d'abord comparé les activités biologiques de plusieurs VDA. Une classe en particulier a attiré notre attention sur laquelle seules quelques études avaient été menées. Cela nous a permis de sélectionner des pistes avec un espace chimique exploitable pour concevoir des scaffolds originaux. Cette thèse présentera les analogues qui ont été synthétisés, leur viabilité cellulaire sur les HUVEC (cellules endothéliales de la veine ombilical humaine) et leur activité sur l'inhibition de la polymérisation de la tubuline (ITP). / Angiogenesis is a vital phenomenon in many physiological processes such as embryonic development or wound healing. But it is also a pathological process involved in the growth of malignant tumors, in the development of metastases and in diseases such as endometriosis or age-related macular degeneration (AMD) and osteoarthritis. Pathological neovasculature is dense and disordered in contrast to physiological neovasculature, which makes it an attractive therapeutic target. Vascular Disrupting Agents (VDA) are a new class of bioactive molecules that selectively destroy tumour neovasculature and shut down blood supply to solid tumours, causing extensive tumour cell necrosis.1 Among small molecule VDAs, tubulin-binding agents are mostly represented. The process of angiogenesis within osteoarthritis as well as the mode of action of VDA leads us to consider the use of its last as a new anti-osteoarthritis treatment. In the search for novel VDA scaffolds, we first compared the biological activities of several VDA. One class in particular attracted our attention on which only a few studies had been conducted. This allowed us to select leads with exploitable chemical space to design original scaffolds. These thesis will present analogs which were synthesized, their cell viability on HUVEC (human umbilical vein endothelial cells) and their activity on tubulin polymerization inhibition (ITP).

The diploma thesis deals with the capability assessment of an optical coordinate measuring machine according to VDA 5. The capability assessment is an effective tool for deciding whether the evaluated measuring machine is capable for the intended use and under which conditions its use is possible. The theoretical part of the thesis is devoted to the analysis of coordinate measuring machines, with a closer focus on a subset of optical measuring machines and the analysis of their capability assessment procedures. In the practical part of the thesis, the selected procedure is applied on the specific measuring machine Micro-Vu Sol 311. The main contribution of this thesis is a description of the possibilities of the considered coordinate measuring machine for its further use in the educational process at the Faculty of Mechanical Engineering of Brno University of Technology.

Tese (Doutorado em História)-Universidade de Brasília, Departamento de História, 2010. / Submitted by Luiza Moreira Camargo (luizaamc@gmail.com) on 2011-07-07T15:19:11Z No. of bitstreams: 1 2010_MarthaRosaFigueiraQueiroz.pdf: 2392306 bytes, checksum: f65c6f0033bf80b1251637277ea8826a (MD5) / Approved for entry into archive by Jaqueline Ferreira de Souza(jaquefs.braz@gmail.com) on 2011-07-08T18:34:27Z (GMT) No. of bitstreams: 1 2010_MarthaRosaFigueiraQueiroz.pdf: 2392306 bytes, checksum: f65c6f0033bf80b1251637277ea8826a (MD5) / Made available in DSpace on 2011-07-08T18:34:27Z (GMT). No. of bitstreams: 1 2010_MarthaRosaFigueiraQueiroz.pdf: 2392306 bytes, checksum: f65c6f0033bf80b1251637277ea8826a (MD5) / O Movimento Negro contemporâneo – aqui identificado como o conjunto de ações e instituições voltadas para a valorização da cultura negra –, a criminalização do escravismo e o combate ao racismo – práticas empreendidas pelos africanos e seus descendentes desde a instauração do escravismo até a presente data, e que tem no mito da democracia racial o grande obstáculo a ser vencido –, constituem o campo de discussão problematizado por esta pesquisa. Apesar desta amplitude temática e temporal, a diversidade interna presente no Movimento, assim como as suas múltiplas estratégias, nem sempre expostas, dão a entender que, malgrado o esforço em contrário, não se trata de um corpo homogêneo, o Movimento Negro. Esta perspectiva alimenta a grande lacuna quanto às trajetórias dos movimentos negros contemporâneos, em especial as experiências nordestinas. Neste sentido, o presente trabalho se insere no campo dos estudos dedicados à resistência político-cultural afro-brasileira, tendo como aporte teórico o enfoque da história cultural. A pesquisa objetiva abordar as práticas discursivas do Movimento Negro na cidade do Recife, concebendo sua pluralidade e subjetividade, e visa compreender o processo de inserção de organizações oriundas do Movimento Negro no carnaval do Recife, no período de 1979 a 1995. Toma-se o espaço de entrecruzamento da militância política com o carnaval, compreendido como lócus privilegiado de observação, na qual se busca perceber as estratégias utilizadas pelos movimentos negros para garantir a presença de seus discursos na cena carnavalesca. Privilegiamos as ações tecidas por meio da circulação de pessoas, ideias, discursos e representações de forma a expor a circularidade horizontal entre os distintos segmentos do MN. Neste sentido, as trajetórias entrecruzadas do MNU-PE e seus antecessores com os primeiros afoxés e com o maracatu Leão Coroado, especificamente nos carnavais de 1986 e 1987, constituíram-se em práticas discursivas capazes de garantir a inserção dos discursos dos movimentos negros no universo carnavalesco recifense no período abordado. _______________________________________________________________________________________ ABSTRACT / The contemporary Black Movement - here identified as the set of actions and institutions dedicated to the promotion of black culture – the slavery criminalization and the fight against racism - practices undertaken by Africans and their descendants since the introduction of slavery until nowadays, and which the myth of racial democracy is the great obstacle to be overcome – all this issues constitute the field of discussion problematized by this research. Despite this thematic and temporal wide range, the internal diversity in this movement, as well as their multiple strategies which are not always exposed, suggest that, despite efforts to the contrary, it is not a homogeneous body, the Black Movement. This approach feeds the large gap about the trajectories of the contemporary black movements, mainly on the Northeastern experience. In this sense, this work is in the study field devoted to the African-Brazilian political and cultural resistance, which has as a theoretical approach cultural history. The research aims to address the discursive practices of the Black Movement in Recife, by designing its plurality and subjectivity, and aims to understand the organizations integration process from the Black Movement in the carnival of Recife, in the period 1979 to 1995. It takes the space of the political activism intertwining with the carnival, understood as the locus of observation, in which he seeks to understand the strategies used by black movements to ensure the presence of his speeches in the carnival scene. We prioritized the actions woven through the movement of people, ideas, discourses and representations in order to expose the circularity horizontally among different segments of the MN (Black Movement). In this sense, the intersecting trajectories of MNU-PE (Unified Black Movement in Pernambuco) and its predecessors with the first afoxés and maracatu Leão Coroado (Crowned Lion), specifically in the carnivals of 1986 and 1987, were constituted in discursive practices which ensure the inclusion of speeches of black movements in the Carnival universe in Recife at the mentioned period.

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Les résistances aux traitements actuels contre le cancer imposent de trouver de nouvelles cibles thérapeutiques. Une de ces cibles est le réseau vasculaire assurant un apport suffisant en nutriments et en oxygène à la tumeur, et permettant l’apparition de métastases. Détruire la vascularisation de la tumeur par l’utilisation d’agents antivasculaires (VDA)revient à l’asphyxier et à l’affamer, inhibant ainsi la prolifération des cellules tumorales et empêchant le processus métastatique. L’objectif de ce travail de thèse a été d’étudier des analogues contraints de l’isocombrétastatine A-4 (isoCA-4), une molécule phare du laboratoire, ayant un excellent pouvoir d’inhibition de la polymérisation de la tubuline et présentant une activité antivasculaire. Ces structures dont la double liaison est incluse dans différents types de cycles C,ont été étudiées également afin d’évaluer l’influence de l’angle dièdre formé par les noyaux A et B sur les activités biologiques des divers types de structures. Préalablement sélectionnés par modélisation moléculaire, ces analogues contraints sont de type 1-arylnaphtalène, 5-arylbenzoxépine ou 4-arylchromène et ont été préparés par des voies d’ accès originales développées dans le cadre de cette thèse. Parmi les composés synthétisés, l’analogue de type benzoxépine 3-53est aussi cytotoxique que l’isoCA-4 et possède un pouvoir d’inhibition de la polymérisation de la tubuline équivalent. Une évaluation plus poussée de son profil biologique, ainsi que celle des meilleurs représentants de chaque série chimique est actuellement en cours. / Most tumor cells rely on an efficient vascular supply for their survival, making the tumor vasculature an attractive target for anti-cancer therapy. This thesis aimed at the design and synthesis of constrained analogues of isocombretastatin A-4(isoCA-4), an antivascular agent developed in the laboratory, which exerts excellent cytotoxicities against a large panel ofcancer cell lines, and strongly inhibits tubulin polymerization. Conformationally restricted analogues of isoCA-4,featuring 1-arylnaphthalene, 5-arylbenzoxepine or 4-arylchromene skeletons were designed by computational studies andprepared by novel synthetic strategies. Of all synthesized compounds, benzoxepine analogue 3-53 strongly inhibits tubulinpolymerization and shows excellent cytotoxicities against several human cancer cell lines.

Master’s thesis describes statistical process control as a support for company management. Statistical process control methods and tools are introduced. Requirements for automotive industry are stated specifically for IATF 16949 standard and VDA 6.3 process audit method. Thesis presents current state in company Sanmina-SCI Czech Republic s.r.o regarding statistical regulation. Applies statistical process controls into the new process considering automotive requirements. It is all happening together with a new business introduction of automotive customer.

Lack of technical cleanliness and particle contaminations in Lithium-ion battery manufacturing affect the performance of batteries which are a risk for the safety and quality of the product. Therefore, part of the manufacturing process occurs inside the Clean and Dry room area to maintain technical cleanliness. This paper aims to provide a framework to control particle contamination inside the Clean and Dry room and strengthen the product's quality and safety. A literature study was conducted, which was completed by a field study at Northvolt Labs in Västerås to achieve the study's aims. The study contributes to existing theories by providing a framework to find root causes of particle contamination in the manufacturing process based on the existing literature and standards. The Six Sigma problem-solving methodology DMAIC was implemented to conduct the field study. A risk assessment was conducted to find the possible threats toward technical cleanliness in the cell assembly process. The risk sources were identified by implementing measurement methods from relevant standards. The results indicate a high risk for technical cleanliness are coming from the decontamination method, material, machines, and environment. Furthermore, several recommendations were given that are expected to decrease the amount of nonconformity in the process. / Brist på teknisk renhet och partikelföroreningar vid tillverkning av litiumjonbatterier påverkar dess prestanda och utgör en risk för produktens säkerhet och kvalitet. Därför sker en del av tillverkningsprocessen i ett Clean & Dry rum för att upprätthålla teknisk renhet. Denna uppsats syftar till att ge ett ramverk för att kontrollera partikelföroreningar och därmed stärka produktens kvalitet och säkerhet. För att uppnå syftet genomfördes först en litteraturstudie vilket vidare kompletterades med en fältstudie vid Northvolt Labs i Västerås. Studien bidrar till befintliga teorier genom att tillhandahålla ett ramverk för att hitta och åtgärda rotorsaker till partikelkontaminering i tillverkningsprocessen baserat på befintlig litteratur och standarder. Sex Sigma problemlösningsmetoden DMAIC implementerades för att genomföra fältstudien. En riskbedömning genomfördes för att hitta riskfyllda aktiviteter i processen. Vidare implementerades mätmetoder från relevanta standarder för att mäta kontamineringsnivån. Resultaten indikerar stor risk för tekniskrenhet från saneringsmetoder, material, maskiner och miljön. Vidare rekommenderas flera åtgärder för att underhålla tekniskrenhet vilka förväntas minska avvikelser i processen.

This study analyzes current trends in metrology in the field of portable coordinate measuring machines and describes current methods for measurement system and process evaluation. Obtained knowledge is applied, in order to evaluate the capability of measurement system, which consists of articulated measurement arm and measurement standard.

Yes / Despite significant preclinical promise as anticancer agents, vascular-disrupting agents have yet to fulfil their clinical potential due to systemic toxicities. ICT2588 is a tumour-selective MT1-MMP-targeted prodrug of azademethylcolchicine, ICT2552. We investigate activation of ICT2588 and subsequent release of ICT2552 in tumour cells, and examine its ability to induce G2/M cell cycle arrest. We also explore synergism between ICT2588 and ATR inhibition, since colchicine, in addition to its vascular-disrupting properties, is known to induce G2/M arrest, DNA damage, and trigger apoptosis. Several ATR inhibitors are currently undergoing clinical evaluation. The cellular activation of ICT2588 was observed to correlate with MT1-MMP expression, with selective release of ICT2552 not compromised by cellular uptake and prodrug activation mechanisms. ICT2588 induced G2/M arrest, and triggered apoptosis in MT1-MMP-expressing cells, but not in cells lacking MT1-MMP expression, while ICT2552 itself induced G2/M arrest and triggered apoptosis in both cell lines. Interestingly, we uncovered that the intracellular release and accumulation dynamics of ICT2552 subsequent to prodrug activation provided synergism with an ATR inhibitor in a way not observed with direct administration of ICT2552. These findings have important potential implications for clinical combinations of ICT2588 and DNA repair inhibitors.