Zugl.: Aachen, Techn. Hochsch., Diss., 2008. / Hergestellt on demand.

The main aim of this thesis is to create a library in TwinCAT PLC for Beckhoff motion control without NC task. This library is targeted for less performance controllers. The next part deals with creating a PLC application for motion control with digital I/O variables or with serial line. A Windows application will be created to configure the main parameters of motion control in the PLC Application.

Embora o melanoma represente apenas 4% das neoplasias malignas da pele, é considerado a mais grave por ser altamente etal. Em virtude da via MAPK (Mitogen activated protein kinase) estar intimamente ligada ao descontrole da proliferação celular, especialmente em melanoma, esta via se tornou um alvo para o desenvolvimento de terapias direcionadas a oncogenes, como os potentes quimioterápicos Vemurafenibe (inibidor da mutação V600E em BRAF - BRAFV600E) e Trametinibe (inibidor de MEK). Cada vez mais, melhores taxas de respostas vêm sendo alcançadas com os novos medicamentos, porém a maioria dos pacientes está sujeita a recidivas após 7 meses de tratamento devido ao desenvolvimento de quimioresistência, justificando a constante busca por novos compostos terapêuticos. Dados de nosso laboratório indicam que 4-nerolidilcatecol (4-NC) induz aumento na expressão de p53, produção de ROS e dano ao DNA, culminando em apoptose dependente de caspase-3 em células de melanoma por ser um inibidor proteassomal. Além disto, o 4-nerolidilcatecol (4- NC) demonstrou efeito inibitório na proliferação de células de melanoma em modelo de cultura organotípica de pele. Desta forma, este projeto visa avaliar a possibilidade de superação da quimioresistência aos inibidores de BRAF e de MEK, utilizando terapias combinatórias com 4-NC em células de melanoma humano resistentes a estes inibidores. Primeiramente, linhagens celulares de melanoma resistentes aos inibidores de BRAF (R) e BRAF/MEK (DR) foram geradas a partir de células parentais BRAF mutadas (P) e caracterizadas por MTT, microscopia de fluorescência e western blotting. Estas células foram submetidas ao tratamento com 4-NC que apresentou citotoxicidade na concentração de 30µM, inibição de formação de colônias e diminuição na invasão em modelos in vitro de culturas 2D e 3D em todas as linhagens estudadas (P, R e DR). O 4-NC foi ainda capaz de induzir estresse de retículo endoplasmático com indução de apoptose. Visando a explorar o efeito terapêutico in vivo do 4-NC, outro estudo foi conduzido em animais submetidos a enxerto xenográfico com células parentais de melanoma NRAS mutadas. Após desenvolvimento do tumor, os animais foram tratados 3 vezes por semana durante 3 semanas com 4-NC (10 mg/kg) por via i.p. O 4-NC foi capaz de inibir em até 4 vezes o crescimento dos tumores xenográficos (4/10) quando comparado com os controles, com remissão completa do tumor em um animal. A expressão de p53 e PARP clivada foi aumentada nos tumores dos animais tratados, sugerindo apoptose. A expressão gênica de MMP2 e MMP14 estava diminuída nas mesmas amostras, demonstrando o papel do 4-NC na inibição da invasão do melanoma in vivo. Finalmente, a toxicidade sistêmica do 4-NC foi avaliada nas mesmas doses empregadas no ensaio in vivo de tumorigênese. A baixa toxicidade observada nos ensaios toxicológicos com tratamentos sub-crônicos com 4-NC e a citotoxicidade demonstrada em modelos xenográficos nos leva a considerar este composto como promissor para estudos futuros e sua aplicação no tratamento do melanoma cutâneo humano, incluindo pacientes resistentes aos inibidores de BRAF e MEK. / Melanoma accounts for only 4% of malignant neoplasms of the skin, but is considered the most serious because it is highly deadly. Because the MAPK (Mitogen activated protein kinase) pathway is closely linked to the lack of control of cell proliferation, especially in melanoma, this pathway has become a target for the development of oncogene-targeted therapies, such as the potent chemotherapeutic agents Vemurafenib (V600E mutation inhibitor in BRAF - BRAFV600E) and Trametinib (MEK inhibitor). Increasingly, better response rates have been achieved with the new drugs, but most patients are subject to relapses after 7 months of treatment due to several mechanisms, which justify the constant search for new therapeutic compounds. Data from our laboratory indicate that 4-nerolidylcatechol (4-NC) induces increased p53 expression, ROS production and DNA damage, culminating in caspase-3 dependent apoptosis in melanoma cells. The 4-NC compound demonstrated an inhibitory effect on melanoma cell proliferation in an organotypic skin culture model. Thus, this project aims to evaluate the possibility of overcoming the existing chemoresistance to BRAF and MEK inhibitors, using 4-NC combinatory therapies in human melanoma cells resistant to these inhibitors. Firstly, melanoma cell lines resistant to BRAF (R) and BRAF / MEK (DR) inhibitors were generated from naive cells mutated BRAF (N) and characterized by MTT, fluorescence microscopy and western blotting. These cells were submitted to 4-NC treatment that showed cytotoxicity with 30 µM, inhibition of colony formation and decrease in invasion in 2D and 3D in vitro models in all cell line studied (N, R and DR). Furthermore, 4-NC was able to induce endoplasmic reticulum stress with apoptosis induction. In order to explore the in vivo therapeutic effect of 4-NC, an additional study was conducted using xenograft model with NRAS-mutated melanoma cell line. After tumor development, the animals were treated 3 times per week for 3 weeks with 4-NC (10 mg / kg) by i.p. injection. 4-NC was able to inhibit up to 4- fold the growth of xenograft tumors (4/10) when compared to controls, with complete tumor remission in one animal. Cleaved PARP and p53 expression were increased in the tumors of treated animals, suggesting apoptosis. MMP2 and MMP14 gene expression were decreased in the same samples, demonstrating the role of 4-NC in inhibiting melanoma invasion in vivo. Finally, the systemic toxicity of 4-NC was evaluated at the same doses employed in the in vivo tumorigenesis assay. The low toxicity observed in the toxicological assays with sub-chronic 4- NC treatments and the demonstrated cytotoxicity in xenograft models leads us to consider this compound as promising for future studies and its application in the treatment of cutaneous human melanoma, including patients resistants to BRAF and MEK inhibitors.

This diploma thesis is focused on advanced NC programming using macros and user cycles. The first part deals with theory of programming and machining of thin-walled parts. The second part contains practical examples of creating cycles, including their graphical support, for individual thin-wall milling strategies. Everything is explained in detail and work can serve as a guide for programmers or wider professional public.

This Master’s thesis is focused on capatilibities of software SinuTrain Sinumerik Operate version 4.8 SP1. In the first part is comparison of control systems and their options. The next part discusses programming method in CNC machining.In the last part there are a practical examples of programming, simulation of their production and technical-economic evaluation.

The master´s thesis demonstrates the SinuTrain Operate 2.6 tools for programming of CNC machine tools. In the first part is done integrating the control system Sinumerik 840D to the most widely used control systems of CNC machine tools and described NC programming methods. The next part of the thesis involves the preparation of technical documentation machined component (front hub on a bicycle) and production design created by using ISCAR company tools. The final part of the thesis is dedicated to creating the NC program and verification of simulation.

This thesis illustrates the potential use of software SinuTrain for programming CNC machine tools on the component Sugar Bowl. First of all, Sinumerik 840D control system - ShopTurn is briefly positioned among other control systems. Subsequently, the technological preparation of production is processed for the two alternatives. The first one is production version from the rod blank 160 mm and the second one is production variant from a pre-cast. NC programs are created for the production of components of both technological options of Sugar Bowl in the software SinuTrain 6.3 - 6.4 V Open ShopTurn. The variants of technological solutions are compared with each other in the technical-economic evaluation. The pre-cast variant is better for manufacturing more than 50 pieces of the Sugar Bowls.

In the United States, political and social attention to child health care remains insufficient, as it has for decades, especially that which serves the needs of low-income families. In response to this widespread negligence, many communities around the country have developed innovative programs to meet the needs of disadvantaged infants and children. That need for coordinated health services exists among poor children in the Roanoke Valley. The local solution has developed since 1988 as the Children's Health Investment Project (CHIP). This thesis explores, from a geographic perspective, how the relationship between enrolled families and their providers affects attitudes and perceptions toward health care services made available through CHIP. Also, the implications of the current spatial distribution of CHIP participants are examined for geographic relevance. / M.S.

Ernest Alfred Walter George Aris FZS, SGA, (1882-1963) was born in Islington and moved to Bradford where he spent his formative years and attained a diploma at the Bradford Technical College of Fine Art in 1900. Aris was a professionally trained commercial artist, author, and prolific illustrator of 170 children’s and natural history books. He also illustrated over 250 books for other authors, including Enid Blyton, Beatrix Potter, and May Byron, as well as contributing to a number of leading periodicals, magazines and newspapers. Aris was not a member of any of the active artists’ clubs or societies and was possibly shunned by his contemporaries and peers, who considered him unoriginal and an unscrupulous opportunist. Volume I of this thesis seeks to examine these suggestions and assesses why Aris’s name, despite his significant output, has remained relatively anonymous and why much of his legacy appears to have been unidentified, overlooked or forgotten. Chapter 1 discusses the historical influences of anthropomorphism on Aris’s style and those of his immediate predecessors. I have categorised Aris’s books into three periods for this appraisal and examined his technical attributes and qualities, together with his trademark features and characteristics, with the purpose of identifying what makes Aris’s creative design instantly recognisable and his output of illustration so distinctive. Chapter 2 discusses Aris’s relationship with the children’s author and illustrator, Beatrix Potter. Aris holds a unique place in history in that he was commissioned by Beatrix Potter to provide illustrations for her book and was the only artist with whom she seriously contemplated a professional working partnership (1916). However, Frederick Warne and Beatrix Potter later accused Aris of plagiarism and of exploiting any opportunity to achieve a commercial advantage. There is an argument to suggest that Aris’s affiliation with Potter and the allegations of plagiarism had a significant impact on his long term reputation and was possibly the reason for adopting the pseudonym Robin A. Hood. Chapter 3 examines the creative scope and features of Aris’s prestigious commercial partnerships. These start from the beginning of his professional career at the turn of the twentieth century, which coincided with the technical development and advancement of the colour picture postcard. Aris was at the forefront of this revolution, designing several series of comic and humorous postcards for leading printers that are now associated with and representative of a bygone era. In 1915 Aris was commissioned to design six tram posters, which were selected by Frank Pick at London Transport, as part of the National Collection of Posters. Pick single handedly revolutionised poster art in Britain and was responsible for establishing the national collection, where these posters now reside and have remained forgotten and out of sight for the last century. In the 1920s the trend for collecting novelty cigarette cards enabled Aris to produce a number of outstanding natural history designs as well as the infamous Frisky series, where his mischievous sense of humour is much evident in his trademark characters. Perhaps Aris’s final and greatest legacy, however, lies in the legendary Cococubs campaign for Bournville Children’s Cocoa, which was described as ‘one of the cleverest publicity schemes of the year.’1 The success of the advertising campaign meant demand outstripped supply of the product, as youngsters eagerly sought the ‘free toy in every tin’ promotional figurines that Aris designed (1934-1936). Volume II of this thesis comprises of a unique catalogue of Aris’s creative output over fifty years and spans a range of commercial fields of art. The catalogue is divided into four parts. Part one consists of Aris’s literary publications, with a detailed bibliographic record and image of the cover of each book that he wrote and illustrated under his own name and pseudonyms, as well as prominent books Aris illustrated for other eminent authors and a compendium list of books Aris illustrated for authors and other publications. Part two is a record of Aris’s commercial work, including the early series of pictorial postcards that he completed for leading quality publishers at the start of his career (1904-1909) and the six pictorial natural history posters, which Aris was commissioned to undertake for the London Transport tram system (1915). Part three comprises of Aris’s collectables and contains the four unique series of cigarette cards that Aris designed for leading tobacco manufacturers (issued 1929-1935). Part four includes a comprehensive description of each of the limited editions and subtle colour variants of the Cococub lead figurines inserted into Bournville Children’s Cocoa (1934-1936). The aim of the thesis is to justify why I believe Aris deserves further merit for his contribution within the field of illustration and commercial artwork. I have sought to highlight the factors that make his contribution and the success of his creative designs within these different fields so significant. 1 The Grocery and the Provision Merchant Journal, November 1934, p. 276.

The aim of this research is to understand and explain designers - what makes them tick, what motivates them and why they do things in the way that they do. A research approach specific to people, being designers, and the social science framework associated with Pierre Bourdieu has been rigorously engaged. Designers have been spoken to face-to-face and given the opportunity to raise their concerns so that their engagement with design production is illuminated and considered. A series of interviews has been carried out with practising designers. The early interviews exposed areas of interest that could best be investigated by targeting older designers who could recount the changes in design production they had witnessed during their working lives. This life history approach has yielded social as opposed to technical descriptions of design practice and has identified significant technological and organisational changes that have affected designers in the past 30 years. The design habitus is a system of dispositions that enables designers to act as they do and be successful in such a complex, interactive activity as designing. Designers display the habitus through their practice and their interactions with other people, with the products they design and the machinery they use when designing. They make distinctions about the products of their activity on through designers’ continuous physical engagement with the objects of their work and their design colleagues. Their attitude to technology is typified by a willingness to embrace the new; they create new things themselves and this leads them to adopt new tools and adapt them to do their job.