O câncer de mama é uma das neoplasias malignas mais comuns que afetam mulheres de todo o mundo. No Brasil, o Estado do Rio Grande do Sul tem índices de incidência e mortalidade por câncer de mama que situam-se entre os maiores do país. Aproximadamente 5-10% dos diagnósticos são causados por mutações germinativas em genes de predisposição entre os quais estão BRCA1 e BRCA2, associados à Síndrome de Câncer de mama e Ovário Hereditários (Hereditary Breast and Ovarian Cancer Syndrome ou HBOC, OMIM #114480).A identificação dos casos hereditários de câncer de mama é importante porque indivíduos afetados apresentam risco cumulativo vital muito superior ao da população para o desenvolvimento de câncer, porque familiares de um afetado podem estar igualmente em risco porque há medidas de rastreamento intensivo e intervenções preventivas que podem diminuir significativamente o risco de câncer em portadores de mutação. O diagnóstico molecular da síndrome HBOC é laborioso e caro devido à heterogeneidade molecular da doença. Famílias que apresentam características indicativas de uma síndrome de predisposição ao câncer de mama e ovário hereditários, mas que são negativas para mutações pontuais em BRCA1/2 vêm sendo testadas para grandes rearranjos visto que essas anormalidades têm sido consideradas como respondendo por, no mínimo, 10% do todos os casos HBOC com mutação identificável, incluindo grandes deleções ou duplicações. Um estudo recente de Portugal, demonstrou que um rearranjo fundador no exon 3 de BRCA2 ocorre em por 8% das famílias HBOC do Norte do país. Os objetivos deste trabalho incluíram a verificação da freqüência e caracterização de rearranjos gênicos nos genes BRCA1 e BRCA2, incluindo a mutação fundadora c.156_157insAlu no exon 3 de BRCA2 em famílias brasileiras dealto risco para a síndrome HBOC. Em um grupo de 145 indivíduos em risco nãorelacionados rastreados para a mutação fundadorac.156_157insAlu no exon 3 de BRCA2 foram encontrados 3 portadores da mutação (prevalência de 2%). Em um grupo de 145 indivíduos de risco não-relacionados rastreados para rearranjos gênicos em BRCA1 e BRCA2 pela técnica de MLPA (multiplex ligation-dependent probe amplification) foram identificados 4 portadores de mutação germinativa, sendo a mutação em dois deles um rearranjo gênico no gene BRCA1 (1,4%) envolvendo sequencias Alu. Rearranjos gênicos em BRCA1 e BRCA2 são responsáveis por uma parcela das mutações em famílias HBOC Brasileiras. O presente estudo, envolvendo uma série grande de famílias com o fenótipo da síndrome HBOC, não identificou novos rearranjos fundadores, no entanto, demonstrou a presença de rearranjos tanto em BRCA1 quanto em BRCA2, reiterando a importância da busca ativa por estas alterações, que dificilmente são identificadas por técnicas convencionais de sequenciamento gênico. A técnica de MLPA associada a um protocolo específico para detecção da mutação fundadora Portuguesa c.156_157insAlu podem ser utilizadas como estratégia inicial de rastreamento de mutações em famílias Brasileiras com a síndrome. Os resultados apresentados aqui, no entanto, indicam que mutações serão identificadas em menos de 10% dos casos utilizando esta estratégia. / Breast cancer is one of the most common malignancies affecting women worldwide. In Brazil, the State of Rio Grande do Sul has incidence rates and mortality from breast cancer are among the largest in the country. Approximately 5-10% of the cases are caused by germline mutations in predisposing genes including BRCA1 and BRCA2 are associated with the syndrome of breast and ovarian cancer Hereditary (Hereditary Breast and Ovarian Cancer Syndrome or HBOC, OMIM # 114480). The identification of inherited cases of breast cancer is important because affected individuals have cumulative risk life much higher than the population for developing cancer because of an affected family may also be at risk because there are measures of intensive screening and preventive interventions that can significantly decrease the risk of cancer in mutation carriers. The molecular diagnosis of HBOC syndrome is laborious and expensive due to the molecular heterogeneity of the disease. Families that have characteristics indicative of a cancer predisposition syndrome of hereditary breast and ovarian cancers, but are negative for mutations in BRCA1/2 have been tested for large rearrangements because these abnormalities have been identified as accounting for at least 10 % of all cases HBOC identifiable mutation, including large deletions or duplications. A recent study from Portugal, the founder showed that a rearrangement in exon 3 of BRCA2 occurs in 8% of HBOC families of the north. The objectives of this work included the verification of the frequency and characterization of gene rearrangements in BRCA1 and BRCA2 genes, including c.156_157insAlu founder mutation in exon 3 of BRCA2 mutations in Brazilian families at high risk for HBOC syndrome. In a group of 145 individuals at risk unrelated traced to c.156_157insAlu founder mutation in exon 3 of 3 found BRCA2 mutation carriers (prevalence 2%). In a group of 145 individuals at risk unrelated screened for gene rearrangements in BRCA1 and BRCA2 by the technique of MLPA (multiplex ligationdependent probe amplification) identified four carriers of germline mutation, and two of the mutation in a gene rearrangement in the gene BRCA1 (1.4%) involving Alu sequences. Gene rearrangements in BRCA1 and BRCA2 account for a portion of HBOC mutations in Brazilian families. This study, involving a large series of families with HBOC syndrome phenotype, no new rearrangements identified founders, however, showed the presence of rearrangements in both BRCA1 and BRCA2, reiterating the importance of active search for these changes, which hardly are identified by conventional techniques of gene sequencing. The technique of MLPA protocol associated with a specific mutation detection founder Portuguese c.156_157insAlu strategy can be used as initial screening for mutations in families with Brazilian syndrome. The results presented here, however, indicate mutations that will be identified in less than 10% of the cases using this strategy.

Made available in DSpace on 2016-03-15T19:30:52Z (GMT). No. of bitstreams: 1 Liliane Cristina Segura.pdf: 1330178 bytes, checksum: 096d5c313a8c52ecbb6e6bfdba3ce05b (MD5) Previous issue date: 2012-04-09 / This research investigated the influence of family and founder on the debt of Brazilian listed companies. Despite the vast national and international literature on capital structure, there are still some doubts about the importance of family in business management. In Brazil, due to the large number of family businesses and concentrated control, is even more evident the need to investigate the issue. Many other studies have treated the family business, others control the concentration and others, the company's founder. The contribution of this work was to separate the companies that have concentrated control in the hands of one family, who have only the family influence, family control, those whose management is familiar and the other whose management is only the founder and also the founder of management company family.Furthermore, it was the separation of concentrated control, significant influence, management controlling, managing shareholder influence. In total 10 different separations were made and tested along the work. The study population consisted of companies listed on Bovespa in 2009, and the final sample consisted of 365 companies. As the main contribution of this work was used as a classification different from the other by separating control and influence,combining the family and the founder and principal actors. To this end, we observed six years (2004-2009), a total of 2190 observations. These data constitute an unbalanced panel that was treated by linear regression using ordinary least squares, then by random effects and finally by fixed effects. These techniques were applied to any distortions that diminish in relation to the control variables that were used and these panels might catch the best way to control and influence of the founder family and management in enterprises. The results show that companies with family control and the ones that have some influence of the founder is present in the sample studied, presented less debt than other companies, going according to national and international studies that claim that family businesses tend to be more conservative in their investments, looking to use more equity than others. However, companies that have concentrated control in the hands of one owner or company presented more debt than the others, confirming the studies that indicate the concentration of capital in Brazil and its consequent tendency to the expropriation of wealth by the majority shareholders . / Esta pesquisa investigou a influência da família e do fundador da empresa no endividamento das empresas abertas brasileiras. Apesar da vasta literatura nacional e estrangeira sobre estrutura de capital, ainda surgem dúvidas sobre a importância da família na gestão das empresas. No Brasil, devido ao grande número de empresas familiares e de controle concentrado, fica ainda mais evidente a necessidade de se investigar sobre o tema. Muitos outros estudos trataram as empresas familiares, outros a concentração de controle e outros, o fundador da empresa. A contribuição deste trabalho foi separar as empresas que possuem controle concentrado nas mãos de uma família, a que possuem apenas a influência familiar,controle familiar, aquelas cuja gestão é familiar e as outras cuja gestão é apenas do fundador e também gestão do fundador em empresas familiares. Além disso, fez-se a separação de controle concentrado, influência significativa, gestão do controlador, gestão do acionista influente. No total, 10 separações foram feitas e testadas ao longo do trabalho. A população estudada foi das empresas listadas na BM&FBovespa no ano de 2009, e a amostra final constituiu de 365 empresas. Como principal contribuição deste trabalho foi utilizada uma forma de classificação diferente dos demais, separando controle e influência, combinando a família e o fundador como intervenientes principais. Para isto, foram observados 6 anos (de 2004 a 2009), num total de 2190 observações. Esses dados constituíram um painel desbalanceado, que foi tratado pelos métodos de regressão linear por meio dos Mínimos Quadrados Ordinário, depois por efei tos aleatórios e por fim, por efeitos fixos. Estas técnicas foram aplicadas para que se diminuíssem eventuais distorções em relação às variáveis de controle que foram utilizadas e esses painéis pudessem captar da melhor forma a influência do controle e gestão familiar e do fundador nas empresas. Os resultados mostram que possuem alguma influência familiar e do fundador se apresentam, na amostra estudada, menos endividadas do que as outras empresas, indo de acordo com os estudos nacionais e internacionais que afirmam que as empresas familiares tendem a ser mais conservadoras em seus investimentos, procurando utilizar mais capital próprio do que de terceiros. No entanto,empresas que possuem o controle concentrado nas mãos de um só proprietário ou empresa se mostraram mais endividadas do que as demais, confirmando os estudos que indicam a concentração de capital no Brasil e sua conseqüente tendência à expropriação de riqueza por parte dos acionistas majoritários.

The diploma thesis deals with a specific area in school management, namely the influence of the founder on the quality of the school. The basic content of this work is the relationship between the founder and the school and the influence of the founder on the quality of the school according to the criteria of a quality school of the Czech School Inspectorate. The work, based on the sources of work, defines the basic and related concepts with the management of the school, describes the differences in the management of the school with regard to its founder. Specifically, it monitors a public school, where the founder is a municipality, and a church school, where the founder is a church legal entity of a registered church, as the schools of these founders are the subject of research. The thesis describes the criteria of a quality school of the Czech School Inspectorate and also presents documents that regulate the relationship between the founder and the school principal and set requirements for the quality of the school abroad, specifically in the Slovak Republic. The research part of the thesis analyzes the issue in two schools, the same type, different founder and examines its differences and the consequences that it brings with it in practice. It focuses on whether or how different founders...

The thesis is a biography of the last member of the Czechoslovak legions Alois Vocásek (1896 - 2003). His long life story is presented chronologically. The author describes the period of his childhood and adolescence, participation in the First World War, service in the Czechoslovak legions, life in Czechoslovakia under German occupation and after the defeat of Nazism. The greatest attention is devoted to his service in the Czechoslovak foreign army and his political positions during the occupation. These two historical stages form the main part of the master's work. Life story is confronted with archival materials.

My dissertation consists of two chapters exploring several aspects of empirical corporate finance with a special focus on founder CEOs and family firms. Chapter 1 focuses on the impact of founder CEO leadership on firm value in publicly listed U.S. firms. Previous research on how founder CEOs affect firm value shows mixed results. Using a natural experiment whereby I measure the impact of the sudden deaths of CEOs during the period 1964–2018, I document that stock prices increase by 1.56% upon founder CEOs’ deaths and decrease by 2.89% upon professional CEOs’ deaths. Next, I develop a novel measure of managerial private benefits and discuss several new insights. First, I document that the positive stock price reactions to the sudden deaths of founder CEOs are mainly driven by the fact that founder CEOs extract two times greater private benefits relative to professional CEOs. Second, segregating private benefits into two parts – nepotism and non-nepotism – I find that investors react to both types of private benefits. Third, investor reactions are more pronounced for tunneling-related disclosed private benefits than for investment-related non-disclosed private benefits. Fourth, investors reactions are more pronounced for private benefits related to underinvestment than for private benefits related to overinvestment. Overall, my paper highlights the impact of CEO leadership styles on shareholder wealth. Chapter 2 examines significant family ownership in publicly listed U.S. firms. Instead of holding a diversified portfolio, family owners, such as the Waltons of Walmart, hold large fractions of their wealth in a single stock. To explain this decision, we build a unique model of ambiguity aversion wherein the family’s information advantage in their firm allows them to more accurately estimate value-at-risk in tail events relative to the diversified portfolio. Using an index of macroeconomic uncertainty, we find a strong, negative relation between the uncertainty beta and both family ownership and involvement. Also consistent with our predictions, we document that families with high absolute wealth or risk aversion are unlikely to exit the firm. Our analysis provides an explanation for a family owner’s decision to hold a concentrated stake in a single firm in countries with well-developed financial markets and legal regimes. / Business Administration/Finance

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This dissertation explores the connection between founder personality and organizational culture in founder-led entrepreneurial companies. With a focus on how founder personality affects culture, it draws from the literature in upper echelon/top management teams, family business and organizational psychology – notably the Attraction-Selection-Attrition (ASA: Schneider, 1987) and Person-Organization fit (P-O: O'Reilly, Chatman, & Caldwell, 1991) theories. Using a combination of ethnographic, psychological and organizational data from the founders and employees of four small firms from multiple industries, and a broader survey study of 336 respondents from 23 firms, it finds support for O’Reilly et al., (2014)’s CEO Personality-Culture link in the small-company setting. It also validates two new findings: 1) that employee personality traits can trump founder personality as an influence on culture, and 2) that founder involvement can moderate the impact of founder personality on culture. The dissertation concludes with plans for further research into the personality-organizational culture effects and thoughts about the applicability of these results for founders and consultants. / Business Administration/Entrepreneurship

In emergent high technology industries, entrepreneurs and their new ventures play a critical role in enhancing economic growth. In these industries, we can easily see some new ventures grow more rapidly to outperform their competitors. However, looking beyond the surface, new ventures’ growth path is idiosyncratic. More specifically, when growing, new ventures pursue different paths in terms of 1) which technologies they develop, 2) which products they make, and 3) what markets they enter. The question that has struck me is why high-tech new ventures differ on these key strategic choices. Building on literature on entrepreneurship, strategy, industry evolution, and network, this dissertation tries to answer this important question by focusing on intra-firm factors, more specifically, the individual and structural attributes of new ventures. Types of founder experience and new ventures’ knowledge structure are examined in depth. My three studies, each presented as a separate essay herein, investigate how individual (i.e. founder experience) and structural attributes (i.e. knowledge structure) affect key strategic choices regarding i) product market scope (Wernerfelt and Montgomery, 1988), ii) technological search scope (Katila and Ahuja, 2002), and iii) the types of new products (Sanchez and Mahoney, 1996; Henderson and Clark, 1990), respectively. In each, I discuss the relevant theories, methodology, data sources, results and implications. By investigating intra-firm factors that trigger different entrepreneurial strategies, my dissertation responds to an important call – micro-foundation of strategy formation – thus filling a key gap in the entrepreneurship literature. / Business Administration/Strategic Management