Made available in DSpace on 2015-04-20T12:31:16Z (GMT). No. of bitstreams: 1 lesemky.pdf: 1202883 bytes, checksum: f8220049d5a1bd344120a49c3ed2500a (MD5) Previous issue date: 2012-12-12 / Cytokeratin 19 (CK 19) is a molecular marker that express cell replication and differentiation, and HER-2 oncogene (Human Epidermal Growth factor receptor-Type 2) is the second member of the human epidermal growth factor receptor (EGFR) family. Its overexpression can mean aggressiveness and poor prognostic in various kinds of tumors, as breast, lung and prostate. In last few decades the diagnostic of morphological changes of the thyroid gland was increased. When being diagnosed with ultrasound, the thyroid nodule prevalence reaches 20% to 30% in the general population. The aim of this prospective study is verify the presence of these markers in thyroid glands in operated non-coastal Amazon inhabitants, and its relationship with pathologic findings. We selected 34 samples of formalin-fixed, paraffin-embedded thyroid tumor tissues, from patients treated at Hospital Adriano Jorge, Manaus, Amazonas. The patients consisted of six men and 28 women, aged between 25 and 76 years, average 47 years. The tissues corresponded to nine multinodular goiter (MNG), seven colloid goiters (CG), five nodular hyperplasia (NH) four adenomatous goiters (AG), three papillary thyroid microcarcinoma (PTMC) and five papillary thyroid carcinomas (PTC). Immunohistochemistry (IHC) staining with CK 19 and HER-2 were performed using the labeled streptavidin biotin peroxidase complex system (LSAB2, DAKO, USA) on all tissues using monoclonal antibodies BA17 mab mouse (Dako M0772, USA) and SP3 rabbit mab (Spring M3034, USA) and inferential statistical analysis applying (Fisher exact test with 5% significance level). HER-2 IHC was not found in all samples. We found a strong positive reactivity for IHC CK19 in all 3 patients with PTMC, in four with PTC, one with MNG, and one with CG. We found focal positivity for CK 19 in one PTC, two MNG, 4 CG and one AG. Statistical significance was found only between CK 19 and histopathology. The results suggest thats HER-2 oncogene has no predictive or prognostic value in thyroid tissues and CK 19 marker showed affinity for PTC, although it is also found in benign tissues with less intensity. / A citoqueratina 19 (CK 19) é um marcador molecular que expressa diferenciação e replicação celular e o oncogene HER-2 (Human Epidermal Growth factor receptor-Type 2), membro da família Fator de Crescimento Epidérmico Humano (EGFR), uma proteína que quando sobre-expressa pode significar maior ploriferação celular e agressividade em vários tipos de tumores, dentre eles mama, pulmão e próstata. Nas últimas décadas vêm aumentando o diagnóstico de alterações morfológicas da glândula tireoide, sendo que quando diagnosticado à ultrassonografia a prevalência do nódulo tireoideano chega a 20% a 30% na população geral. Objetivamos neste estudo prospectivo verificar a presença destes marcadores em glândulas tireoideas operadas em pacientes habitantes em região amazônica não litorânea, e sua relação com as alterações morfológicas encontradas. Foram selecionadas 34 amostras de tecido tireoidiano preservados em formol e armazenados em parafina, de pacientes operados na Fundação Hospital Adriano Jorge, de Manaus, Amazonas. Os pacientes corresponderam a seis homens e 28 mulheres, com idade entre 25 e 76 anos e média de 47 anos. Os tecidos corresponderam a nove bócios multinodulares (BMN), sete bócios coloides (BC), cinco hiperplasias nodulares (HN) quatro bócios adenomatosos (BA), três microcarcinomas papilíferos (MCP) e cinco carcinomas papilíferos da tireóide (CPT). Exames de imuno-histoquímica em busca dos marcadores CK19 e HER-2 foram realizados em todos os tecidos usando anticorpos monoclonais BA17 (mab rato, Dako M0772, EUA) e SP3 (policlonal em coelho, Spring M3034, EUA) e o método esteptavidina-biotina-peroxidade (Kit LSAB, Dako, EUA) e análise estatística inferencial aplicando o teste Exato de Fisher com nível de significância de 5%. Não foi encontrada positividade para o marcador HER-2 em tecidos tireoidianos malignos ou benignos. Foram encontrados positividade média a forte intensidade para CK19 em todos os três pacientes com MCP, quatro CPT, um BMN e um BC. Foram encontrados positividade focal em um CPT, dois BMN, quatro BC e um BA. A análise estatística demonstrou significância estatística somente entre as variáveis CK 19 e tipo histopatológico. Os resultados da amostra analisada demonstraram que a pesquisa no oncogene HER-2 não apresentou presença deste marcador em nenhum dos tecidos tireoidianos, e o marcador CK 19 foi presente em maior intensidade nos casos de Carcinoma que nos tecidos benignos onde foi encontrado.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-09-04T19:51:03Z No. of bitstreams: 2 Dissertação - Paula Lima Magalhães - 2017.pdf: 3829811 bytes, checksum: fc13a75154ee6a0c6c19e4be5ff0208a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-09-15T14:46:40Z (GMT) No. of bitstreams: 2 Dissertação - Paula Lima Magalhães - 2017.pdf: 3829811 bytes, checksum: fc13a75154ee6a0c6c19e4be5ff0208a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-09-15T14:46:40Z (GMT). No. of bitstreams: 2 Dissertação - Paula Lima Magalhães - 2017.pdf: 3829811 bytes, checksum: fc13a75154ee6a0c6c19e4be5ff0208a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-07-31 / Squamous cell carcinoma (SCC) is one of the most common malignant cutaneous tumors in all species, as well as in the human species, ranging from young animals to the elderly. It has development associated with environmental factors such as prolonged exposure to solar rays and epidermal hypopigmentation. According to the literature, 80% of malignancies originate in environmental stimuli, due to exposure to carcinogens. Despite the multifactorial etiology, the search for clarification of the causes and mechanisms of cancer evolution must be incessant, since innumerable neoplasms can be prevented, especially when induced by exogenous factors. The aim of this study was to study canine cutaneous SCC in the light of different histomorphological patterns of the neoplasia, evaluating its immunophenotype response to EGFR and c-erbB2 epidermal growth factor receptors. For that, the cases of canine SCC were analyzed from the archive of the Animal Pathology Sector of the EVZ / UFG from 2006 to 2015. For the epidemiological study, registration information was considered, including breed, sex, age and anatomical location. Regarding the histomorphological evaluation and malignancy criteria, the lesions were classified according to the system recommended by the Müller e Kirk’s. Anti-EGFR (HER1) and anti-c-erbB-2 (HER2) antibodies were used for the immunohistochemical study to better understand the role of these proteins in the mechanisms involved in the genesis, proliferation and evolution of SCC in dogs. Considering the histomorphological and immunophenotypic analyzes, the correlation between its variables was tested, and a correlation was verified between the EGFR immunostaining and the degree of SCC differentiation (r = 0.26, p = 0.02). On the other hand, there was no correlation between c-erbB2 immunostaining and histomorphological differentiation (r = 0.02; p = 0.83). When the correlation between EGFR and c-erbB2 immunoblots was tested, a positive correlation was also observed, but not statistically significant (r = 0.21, p = 0.06). It is concluded that there is a propensity that the increase in EGFR immunoexpression is directly proportional to the degree of SCC differentiation, and that it does not occur with c-erbB2 immunostaining. Also, SCCs in dogs seems to exhibit simultaneous increase of EGF receptor immunostaining. / O carcinoma de células escamosas (CCE) é um dos tumores cutâneos malignos mais comuns em todas as espécies animais, assim como na espécie humana, podendo acometer desde animais jovens a idosos. Tem desenvolvimento associado a fatores ambientais como exposição prolongada aos raios solares e hipopigmentação epidermal. Os estudos revelam que, 80% das neoplasias malignas têm origem em estímulos ambientais, em decorrência a exposição a carcinógenos. Apesar da etiologia multifatorial, a busca pelo esclarecimento das causas e dos mecanismos de evolução do câncer deve ser incessante, pois inúmeras neoplasias podem ser prevenidas, especialmente quando induzidas por fatores exógenos. Assim, este trabalho teve por objetivo estudar o CCE cutâneo canino à luz dos diferentes padrões histomorfológicos da neoplasia, avaliando o seu imunofenótipo quanto aos receptores do fator de crescimento epidérmico EGFR e c-erbB2. Para tal, foram avaliadas os casos de CCE canino provenientes do arquivo do Setor de Patologia Animal da EVZ/UFG no período de 2006 a 2015. Para o estudo epidemiológico foram consideradas as informações de registro, incluindo raça, sexo, idade e localização anatômica. Quanto à avaliação histomorfológica e critérios de malignidade, as lesões foram classificadas de acordo com o sistema preconizado por Müller e Kirk’s. Para o estudo imunoistoquímico foram utilizados os anticorpos anti-EGFR (HER1) e anti-c-erbB-2 (HER2), com o intuito de melhor compreender a participação dessas proteínas nos mecanismos envolvidos na gênese, proliferação e evolução do CCE em cães. Considerando as análises histomorfológica e imunofenotípica foi testada a correlação entre suas variáveis, sendo constatada correlação entre a imunomarcação para EGFR e o grau de diferenciação do CCE (r=0,26; p=0,02). Por outro lado, não houve correlação entre a imunomarcação de c-erbB2 e a diferenciação histomorfológica (r=0,02; p=0,83). Quando testada a correlação entre as imunomarcações de EGFR e c-erbB2, também foi observada correlação positiva, porém sem significância estatística (r=0,21; p=0,06). Conclui-se que há propensão de que o aumento na imunoexpressão de EGFR seja diretamente proporcional ao grau de diferenciação do CCE, sendo que o mesmo não ocorre com a imunomarcação de c-erbB2. Também, os CCE em cães parecem apresentar aumento simultâneo da imunomarcação dos receptores de EGF.

O câncer de mama permanece como segundo tipo de câncer mais frequente no mundo e o primeiro entre as mulheres. Tumores de mama podem ser categorizados pela expressão de receptores como o HER-2 (receptor de fator de crescimento epidermal 2). A hiperexpressão do receptor HER-2 é observada em cerca de 30% dos carcinomas de mama, e está associada a prognósticos desfavoráveis. Os ácidos graxos poli-insaturados (AGPI) , como os ácidos graxos ômega-3, parecem diminuir o risco de câncer de mama. O ácido docosahexaenoico (DHA), um tipo de AGPI ômega-3 parece ter o maior potencial antitumoral no câncer de mama. Alguns mecanismos de ação foram propostos para a ação do DHA no controle do câncer de mama, no entanto, faltam dados para elucidar os mecanismos moleculares do DHA no tecido mamário normal e cancerígeno. Dessa maneira, o objetivo desse trabalho foi avaliar a ação do DHA na modulação da expressão de genes em linhagem celular normal (HB4a), transformada (HB4aC5.2) e de carcinoma mamário humano (SKBR-3). As linhagens estudadas foram tratadas com 100 ?M de DHA ou controle (etanol) durante 72 horas. Após a extração de RNA realizamos a técnica de expressão gênica global (Microarray) para encontrar os genes diferencialmente expressos, em relação ao tratamento com DHA, em cada linhagem celular estudada. Na linhagem normal (HB4a) observamos 174 genes diferencialmente expressos (p<0,01), sendo 136 hiperexpressos e 38 hipoexpressos, na linhagem celular transformada (HB4aC5.2) encontramos 208 genes diferencialmente expressos (p<0,01), sendo 32 hiperexpressos e 176 hipoexpressos. A linhagem do carcinoma mamário (SKBR-3) apresentou 126 genes diferencialmente expressos (p<0,01), sendo 48 hiperexpressos e 78 hipoexpressos. A análise ontológica destes genes permitiu identificar processos biológicos como: adesão celular, diferenciação celular e metabolismo lipídico. Concluímos que o DHA altera o perfil de expressão gênica de maneiras distintas em linhagem normal, transformada e de carcinoma mamário humano. Além disso, encontramos após o tratamento com DHA genes envolvidos com o metabolismo lipídico nas linhagens que hiperexpressam o receptor HER-2 / Breast cancer remains the second most common cancer in the world and first among women. Breast tumors can be categorized by the expression of receptors such as HER-2. Overexpression of HER-2 receptor is associated with unfavorable prognosis.The polyunsaturated fatty acids (PUFAs) omega- 3 appears to decrease the risk of breast cancer. Docosahexaenoic acid (DHA), a type of omega-3 PUFAs, seems to have greater antitumor potential in breast cancer. However, the gene expression profile resulting from the action of DHA in breast cancer has not been elucidated yet. We aimed to examine the effects of DHA on normal breast cell line (HB4a), transformed cell line (HB4aC5.2) and breast cancer cell line (SKBR-3) and using a microarray approach. Cells were treated with 100?M of DHA for 72 hours. We identified 174, 208 and 126 differentially expressed genes after DHA treatment, in HB4a, HB4aC5.2 and SKBR3, respectively. Notably, the molecular pathways for the differentially expressed genes included those related to lipid metabolism, cell growth, molecular transport and cell-to-cell signaling. Where found genes related to overexpression of HER-2 after treatment with DHA. These genes involved in lipid metabolism and were down-expressed after treatment, suggesting a possible mechanism DHA in breast cancer by lipid metabolism control

This thesis deals with general game playing agent systems. On the contrary with common agents, which are designed only for a specified task or a game, general game playing agents have to be able to play basically any arbitrary game described in a formal declarative language. The biggest challenge is that the game rules are not known beforehand, which makes it impossible to use some optimizations or to make a good heuristic function. The thesis consists of a theoretical and a practical part. The first part introduces the field of general game playing agents, defines the Game Description Language and covers construction of heuristic evaluation functions and their integration within the Monte Carlo tree search algorithm. In the practical part, a general method of creating a new heuristic function is presented, which is later integrated into a proper agent, which is compared then with other systems.

The aim of the work was to present the history of board games from a historical- sociological perspective. The theoretical section described the history of board game development, taking into account their role in society. Subsequently, the results of qualitative research conducted among members of the board players community in the Czech Republic were interpreted in practical part. These were complemented by the results of the questionnaire investigation. This gave a comprehensive view of the evolution and transformation in the board player community, as well as the board game itself. So the work presented not only a thousand-year history of board games, but also focused on contemporary board games and their players.

Master of Arts / Department of English / Dean G. Hall / Salman Rushdie's 1999 novel The Ground Beneath Her Feet is ostensibly a rock 'n' roll novel, largely set in the 1960s, that traces the commercial rise of Indian rock star protagonists Vina Apsara and Ormus Cama. As their fame and wealth rise to global status and their stage show comes to entail a logistical complexity of military proportions, it becomes increasingly difficult to discern the couple's earlier countercultural ideals within their new established culture status. I argue that despite the change from countercultural to establishment-based values in the novel's protagonists, Rushdie does make a case in The Ground Beneath Her Feet for the possibility of countercultural efficacy against the commodifying culture of global capitalism (which I refer to as the "Frame"). His recipe for combating the exclusive hierarchies produced by the Frame is a combination of the non-totalizing politics of postmodernism and the subversive potential of uncommodified rock music. I pay close attention to establishing the historical templates--John Lennon of the Beatles and Brian Wilson of the Beach Boys--of the novel's protagonists in an effort to understand the sort of countercultural alternative Rushdie is proposing. I likewise focus on the novel's depiction of the Beach Boys' Smile album, which as a still commercially unreleased record, reinforces Rushdie's imperative in The Ground Beneath Her Feet for an uncommodifying counterculture and works in tandem with his portrayals of the artistic plights of several minor characters in the novel as well.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Breast Cancer remains one of the world’s leading causes of cancer related deaths amongst women. Its treatment has evolved from invasive, highly toxic therapies to treatments that possess a higher specificity and a lower toxicity. Despite improvements in overall survival, many patients do not benefit from these agents because of acquired and/or inherent tumour resistance, which could hinder treatment efficacy. Novel treatment strategies are, therefore, warranted to address these challenges and to significantly improve patient responses. Inhibiting components of the HER-2 signalling pathway can significantly sensitise breast cancer cells to low doses of ionising radiation. The objective of this study was to inhibit key molecular targets of the human epidermal growth factor receptor 2 (HER-2) signalling pathway and expose breast cancer cell lines to doses of radiation, so as to establish potential therapeutic targets that may be amenable to combined modality therapy, and formulate a cocktail of inhibitors to evaluate its radiosensitising capability. This study found that pre-treatment of two breast cancer cell lines (MDA-MB-231 and MCF-7) with a HER-2 inhibitor (TAK-165) had little or no effect on radiosensitivity. However, a radiation enhancement was observed when these cells were pre-treated either with BEZ235, a dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target for rapamycin (mTOR), or a cocktail of TAK-165 and BEZ235. These findings suggest that concurrent inhibition of HER-2, PI3K and mTOR during radiotherapy might improve treatment response of breast cancer patients. / AFRIKAANSE OPSOMMING: Borskanker bly steeds een van die leidende oorsake van sterftes aan kanker in vrouens. Behandeling het vanaf ‘n ingrypende, hoogs toksiese terapie verander na ‘n regimen wat hoogs spesifiek met ‘n laer toksisiteit is. Nogtans trek baie pasiënte geen voordeel uit hierdie nuwe benadering nie, omdat inherente en/of verworwe tumorweerstand daarteen suksesvolle uitkomste verhoed. Nuwe behandelingstrategieë is dus nodig om hierdie uitdagings te bekamp en om resultate in pasiënte aansienlik te verbeter. Inhibisie van komponente van die HER-2-seinoordragkaskade kan borskankerselle gevoelig maak vir lae dosisse van geïoniseerde bestraling. Die doelwit van hierdie studie was om sleutelteikens in die HER-2- seinoordragkaskade te inhibeer en om borskankerselle daarna aan bestralings dosisse bloot te stel. Sodoende word potensiële terapeutiese teikens wat vatbaar is vir gekombineerde modaliteitsterapie geïdentifiseer, waarna ‘n kombinasie van inhibitore geformuleer en geëvalueer kan word ten opsigte van hulle kapasiteit om gevoeligheid vir bestraling te verhoog. Die studie bevind dat voorbehandeling met ‘n HER-2-inhibitor (TAK-165) van borskankersellyne (MDA-MB-231 en MCF-7) min of geen invloed gehad het op stralingsensitiwiteit nie. ‘n Stralingsversterking is egter geïdentifiseer toe die selle vooraf behandel is met óf BEZ-235, ‘n tweevoudige inhibitor van fosforinositied 3-kinase (PI3K) en soogdierteiken vir rapamisien (mTOR), óf ‘n mengsel van TAK-165 en BEZ-235. Hierdie bevindinge suggereer dat gelyktydige inhibisie van die HER-2- seinoordragkaskade, PI3K en mTOR gedurende stralingsterapie moontlik die uitkoms in borskankerpasiënte kan verbeter.

Title: Multi-platform environment for mobile-game development Author: Ivan Vacula Department: Department of Software Engineering Supervisor: RNDr. David Bednárek, Ph.D. Supervisor's e-mail address: bednarek@ksi.mff.cuni.cz Abstract: Smart mobile devices are getting more and more popular these days. But there comes a problem with their expansion as well. Mobile operating systems differ from each other, as do mobile devices themselves, so development across multiple platforms is not simple. Situation is even worse when it comes to games. These need to use limited resources of a mobile device as much as possible, taking into account quick response to user actions, graphical execution et cetera. The first goal of this thesis is to compare existing solutions for multi-platform mobile game development. The second goal is to design a new system. This system must ensure targeting of multiple platforms during mobile game development. Included in this thesis is implementation of the system on two vastly different operating systems as well as implementation of a demonstration game. Keywords: multi-platform, mobile, smartphone, game, development

The concern of this thesis is to discuss different multicriteria games solution concepts. Multicriteria game is a special case from the game theory if the payoff function of at least one player is a vector and the player wants to maximize all the criteria at the same time. The thesis is divided into four chapters. In the first instance a few motivation examples are introduced. Subsequently the history of the multicriteria games is mentioned. The theoretical chapter follows. It contains five sections - introduction of new definitions; the structure of the set of equilibria for two person multicriteria games; searching equilibria points by the help of scalarization of the vector-valued function; introduction of ideal equilibria points and ways how to find them; the comparison of used methods. The last solution concept is demonstrated by the real example. Finally a theoretical chapter with new results is included. 1

This diploma thesis "New urban games and their players" treats the new phenomenon of urban games. The text is based on the classical games theory joined with the latest developments in the area and some relevant concepts of urban sociology. From a sociological point of view this thesis explores urban games as a new leisure time phenomenon and clearly states its characteristics as well as its definition. The main focus lies in examining the recent developments in Czech urban games and describing the variety present in urban games today. Other related topics of urban activities are also explained. The mechanics of urban games is explored in the case study of Compagnie, an urban game that took place in Prague in 2010. In the case study, the urban game basics are shown in order to help the general public to understand it. This work is concluded with a socio-demographic analysis of urban game players based on an enquiry done with the participants of the game. The whole text mixes theoretic approach with practical study of urban games, sociological analysis and participatory observation.