Selection and genetic drift are often competing forces in shaping genetic structure in populations. Genetic drift will often effectively cancel out the effect of selection when population sizes are small, such as in colonizing island populations. On a small island in the Skeppsvik Archipelago in northern Sweden, a newly founded population of Silene dioica has been monitored since it first established around 1993. Though inhabiting an area of merely 173 m2, the population has been shown to exhibit a genetically differentiated patch structure where closely related individuals are tightly grouped, distanced from other family groups. In this study, the effect of selection was evaluated as compared to that of genetic drift. Variation in phenotypic traits in flowers, leaves and stalks were compared to that of neutral markers, in the form of PST and FST measures, to assess a measure of what proportion of differentiation among patches in phenotypic traits could not be attributed to genetic drift. Males and females were analysed separately to obtain measures of sex specific selection. Signs of divergent and stabilizing selection were found in several traits in both males and females despite the small spatial scale and short time since colonization. Further analysis is needed to assess explanations for trait divergence among patches and direction of selection.

A incidência dos tumores adrenocorticais na região sul do Brasil é 10-15 vezes maior que a incidência mundial. Mutações no gene supressor tumoral p53, localizado na região 17p13.1 têm sido identificadas em diversos tumores humanos. Uma distinta mutação germinativa, Arg337His, localizada no domínio de tetramerização da proteína supressora tumoral P53 foi identificada em 35 de 36 crianças da região sul do Brasil. No presente trabalho, investigamos a presença da mutação Arg337His em 71 pacientes não relacionados, 41 adultos e 30 crianças, portadores de tumores adrenocorticais benignos e malignos. Adicionalmente, análise de perda de heterozigose do locus p53, mapa de deleção do cromossomo 17 e instabilidade cromossômica foram estudados em DNA genômico destes pacientes. Nenhum dos pacientes estudados apresentava histórico familial compatível com a síndrome de Li-Fraumeni. Sequenciamento automático permitiu a identificação da mutação Arg337His, em DNA extraído a partir de sangue periférico e/ou tecido tumoral, em 29 (24 crianças e 5 adultos) dos 71 pacientes. Nas 10 famílias em que foi possível analisar o DNA genômico de ambos os pais verificamos que a mutação Arg337His tem caráter hereditário. Por outro lado, esta mutação não foi encontrada em DNA de 160 indivíduos do grupo controle, não relacionados, analisados por sequenciamento automático e/ou digestão enzimática. A análise pareada de DNA gênomico de sangue periférico e de tecido tumoral revelou perda de heterozigose para o locus p53 em 18 de 21 (86%) pacientes portadores da mutação Arg337His. Não observamos correlação entre a presença desta mutação e o comportamento maligno dos tumores. O estudo de dois marcadores polimórficos intragênicos do p53, pelo programa de análise de tamanho de fragmento GeneScan, evidenciou um mesmo haplótipo associado à mutação Arg337His em 91% dos pacientes com tumores adrenocorticais, configurando uma origem comum para esta mutação. O estudo de 6 marcadores polimórficos ao longo do cromossomo 17 (D17S926, VNTRP53, D17S1856, D17S942, D17S1351 e D17S928) em DNA genômico pareado de 29 pacientes demonstrou uma freqüência elevada (81%) de perda do cromossomo 17 em associação à mutação Arg337His. Não observamos correlação entre a perda do cromossomo 17 e a agressividade tumoral nestes pacientes. Instabilidade cromossômica envolvendo os cromossomos 2, 9 e 11 nos 17 pacientes que perderam o cromossomo 17 foi identificada em 47%, 47% e 71%, respectivamente. Perda dos cromossomos 2 e 11 foi evidenciada em tumores benignos e malignos. A perda do cromossomo 9 foi evidenciada exclusivamente nos tumores malignos, assim como a perda concomitante de 3 ou mais cromossomos. Em conclusão, confirmamos uma freqüência elevada da mutação Arg337His em crianças brasileiras com tumores adrenocorticais benignos e malignos. Esta mutação também foi encontrada no grupo de adultos, embora em menor freqüência. Não houve correlação entre sua presença e o comportamento maligno dos tumores adrenocorticais. Efeito fundador para a mutação Arg337His e inativação bialélica do p53, caracterizada pela presença da mutação Arg337His e a perda do cromossomo 17 foram demonstradas na maioria dos casos analisados. Finalmente, a instabilidade cromossômica envolvendo três ou mais cromossomos contribuiu para o diagnóstico de carcinoma adrenocortical / The incidence of adrenocortical tumors in the South region of Brazil is 10 to 15 times higher than the worldwide one. Mutations in the tumor suppressor p53 gene, located in chromosome 17p13.1, have been described in different human tumors. A germline mutation, Arg337His, in the tetramerization domain of the tumor suppressor P53 was identified in 35 of 36 children from the South region of Brazil. In the present study we have searched for Arg337His mutation in genomic DNA of 71 non-related patients, 41 adults and 30 children, with benign or malignant adrenocortical tumors. Additionally, we also analyzed the loss of heterozigosity of p53 locus, deletion mapping of chromosome 17 and chromosome instability, in genomic DNA of these patients. None of the patients had a familial history of Li-Fraumeni syndrome. Automatic sequencing identified the Arg337His mutation in genomic DNA from peripheral leukocytes and/or tumor tissues in 29 (24 children and 5 adults) of these 71 patients. In 10 families in which the study of both parent\'s DNA was possible, the Arg337His mutation was inherited from one of the parents. Sequencing analysis and/or enzymatic restriction showed that this mutation was not present in DNA of 160 non-related control subjects. Paired analysis of genomic DNA of peripheral leukocytes and tumor tissue revealed loss of heterozigosity of p53 locus in 18/21 (86%) patients with Arg337His mutation. There was no correlation between the presence of this mutation and the malignant behavior of these tumors. The study of two intragenic polymorphic markers of p53 through GeneScan software showed the association of the same haplotype with the Arg337His mutation in 91% of patients with adrenocortical tumors, indicating a common origin of this mutation. The study of 6 polymorphic markers along chromosome 17 (D17S926, VNTRP53, D17S1856, D17S942, D17S1351, D17S928) in paired genomic DNA of 29 patients showed an increased frequency (81%) of chromosome 17 loss in association with the presence of the Arg337His mutation. We did not observe any correlation between the loss of chromosome 17 and aggressive tumor behavior in these patients. In the 17 patients who lost chromosome 17, chromosome instability of chromosomes 2, 9 and 11 was identified in 47%, 47% e 71%, respectively. Loss of chromosomes 2 and 11 was observed in benign and malignant tumors, whereas the loss of chromosome 9 was observed exclusively on malignant tumors. Similarly, the concomitant loss of 3 or more chromosomes was only observed in malignant tumors. In conclusion we confirmed an increased frequency of Arg337His mutation in Brazilian children with benign or malignant adrenocortical tumors. This mutation was also found in the adult group, although at a lower frequency. There was no correlation between the presence of the mutation and the malignant behavior of adrenocortical tumor. We demonstrated a founder effect for this mutation and also a biallelic inactivation of p53 characterized by the presence of the Arg337His mutation and the loss of chromosome 17 in most of the cases studied. Finally, chromosome instability involving 3 or more chromosomes contributed for the diagnosis of adrenocortical carcinoma in these

The master`s thesis deals with the evaluation of the management ZIKOS allowance organization. The aim of this work is the cost-benefit analysis and financial analysis to evaluate the management of the organization and propose recommendations for improvement the management of the organization. On the basis of theoretical knowledge referred to in the first part is the second part focuses on the assessment of economics. The third part contains suggestions and recommendations to improve the management of allowance organizations ZIKOS.

This publication-based dissertation covers four independent empirical essays using different methodological approaches that examine the role of social capital, especially networks of supporters in the venture crea-tion process from two perspectives, the financial and the knowledge development perspective. In particular, two of the essays focus on the financing process in crowdinvesting and its stakeholders from the ankles of the entrepreneurs and the investors. The second one also explores the investors’ characteristics, motivations and reactions to signals. Two further essays focus on supporting activities provided by third parties. One analyses the structure of supporters during the founding process and their relationship to the founder by using a novel approach for social capital research. The other essay highlights the special role of founder coaches during the first stages of the venture, including modelling five functional roles. It also analyses the quality of the relationship between founder and coach as well as its challenges. The data highlight that high quality networks and thus its social capital can be strategically created for the benefit of the founder during the venture development process. New insights coming from this thesis advance the current discussion on social capital by expanding it to recent phenomena in entrepreneurship of highly practical nature.:1 Introduction 1.1 Theoretical Foundations of Social Capital 1.2 Perspectives of Social Capital in Management Support 1.2.1 Essay 1: Using Repertory Grid Technique to Explore the Relationship Between Business Founders and Support Agents 1.2.2 Essay 2: Supporting fledgling entrepreneurs through founder coaching in Germany 1.3 PART II Perspectives of Social Capital in Crowdinvesting 1.3.1 Essay 3: The Financing Process of Equity-Based Crowdfunding: An Empirical Analysis 1.3.2 Essay 4: What motivates crowdinvestors? An empirical analysis of investors’ motivation and decision making in equity-based crowdfunding campaigns 1.4 Methodological Considerations 1.5 Conclusion 1.6 Implications for Academia and Practice 1.7 References 2 Essay 1: Using repertory grid technique to explore the relationship between business founders and support agents 3 Essay 2: Supporting fledgling entrepreneurs through founder coaching in Germany 4 Essay 3: The financing process of equity-based crowdfunding - an empirical analysis 5 Essay 4: What motivates crowdinvestors? An empirical analysis of investors’ motivation and decision making in equity-based crowdfunding campaigns

Les ataxies héréditaires sont des désordres neuro-dégénératifs qui causent une ataxie comme symptôme primaire; soit une perte de coordination des mouvements volontaires, un sens de l’équilibre déficient et un trouble à la motricité. Elles forment un groupe cliniquement et génétiquement hétérogène. De ce fait, de nombreuses classifications existent basées sur différents critères. Cependant, le consensus actuel veut que le mode de transmission soit le critère premier de classement. On estime la prévalence mondiale des ataxies héréditaires à 6/100 000 bien que ce nombre diffère entre régions. C’est le cas du Québec où la structuration historique du bassin génétique canadien-français a menée à des effets fondateurs régionaux, ce qui a eu comme conséquence de hausser la prévalence régionale de certaines maladies. L’Acadie est également une région canadienne-française avec des effets fondateurs où le taux de prévalence de certaines ataxies héréditaires est plus élevé. Nous avons recruté huit familles canadiennes-françaises provenant de diverses régions du Québec, ayant un lien génétique plus ou moins rapproché avec l’Acadie, dans lesquelles nous avons observé dix cas d’une forme d’ataxie spastique autosomique récessive relativement légère qui a résistée à l’analyse des gènes d’ataxies connues. Nous avons émis l’hypothèse d’être en présence d’une nouvelle forme d’ataxie à effet fondateur pour la population canadienne-française. Afin d’identifier le gène muté responsable de cette ataxie, un criblage génomique des marqueurs SNP pour les individus recrutés fut effectué. Puis, par cartographie de l’homozygotie, une région de 2,5 Mb fut identifiée sur le chromosome 17p13 dans une famille. Une revue de la littérature nous a permis de constater, qu’en 2007, quatre familles nord-africaines atteintes d’une ataxie dénommée SPAX2 qui présentaient des manifestations cliniques semblables avaient déjà été liées au même locus sur le chromosome 17. Afin de supporter notre hypothèse que les malades étaient porteurs de deux copies de la même mutation fondatrice et de cartographier plus finement notre région d’intérêt, les haplotypes de tous les atteints de nos huit familles furent étudiés. Nous avons établie qu’un intervalle de 200 kb (70 SNP), soit du marqueur rs9900036 à rs7222052, était partagé par tous nos participants. Les deux gènes les plus prometteurs des 18 se trouvant dans la région furent séquencés. Aucune mutation ne fut trouvée dans les gènes SLC25A11 et KIF1C. Par la suite, une analyse de liaison génétique stricte avec calcul de LOD score nous a permis d’exclure ce locus de 200 kb comme étant celui porteur du gène muté causant l’ataxie dans la majorité de nos familles. Nous avons donc conclus que malgré qu’une famille soit homozygote pour une grande région du chromosome 17, l’absence d’Informativité des marqueurs SNP dans la région de 200 kb fut responsable de l’apparent partage d’haplotype homozygote. Le travail reste donc entier afin d’identifier les mutations géniques responsables de la présentation ataxique chez nos participants de souche acadienne. / Hereditary ataxias are neurodegenerative disorders which share ataxia as common feature is manifested by a decrease in limb coordination, imbalance and an unsteady gait. They consist in a clinically and genetically heterogeneous group. Many ataxia classifications have been proposed, however, the current consensus is to first characterize them according to their mode of transmission. Hereditary ataxias as a whole have a prevalence of 6/100 000, with variable estimation between country and region. In the Province of Quebec where the French Canadian genetic pool can be seen has a mosaic of regional gene pools there is clear differences in local variation in the prevalence of different ataxias. Acadia is also a French Canadian region with a history of many founder effects and a higher prevalence for certain hereditary ataxias. We recruit 8 French Canadian families from Quebec and with genealogical links with Acadia in which 10 cases manifest a presumably relatively mild autosomal recessive spastic ataxia of unknown etiology. The shared phenotype and Acadian background raised the possibility that they suffered from a new form of ataxia with a founder effect. To identify the mutated gene causing this ataxia, the individuals recruited were genotyped. By homozygosity mapping, a region of 2,5 Mb was identified in one family on chromosome 17p13. A literature review established that in 2007 four North Africans families segregating also a mild spastic ataxia were linked to the same locus on chromosome 17. To support our hypothesis that our patients were carrier of the same founder mutation we look closer at their haplotype in the region. We defined an interval of 200kb (70 SNP) between markers rs9900036 and rs7222052 shared by all affected cases. The two most promising gene in the interval were sequenced. No mutation was found in SLC25A11 and KIF1C. Thereafter a linkage analysis by LOD score excluded the candidate interval of 200 kb in the majority of our families. We conclude that even if in one family exists a large homozygous region on chromosome 17, the lack of informative SNP in the 200 kb region was responsible for the apparent sharing rather than they shared a common mutation. Further work will be necessary to identify the mutate gene causing the ataxia presentation in these cases of mild spastic ataxia.

Un effet fondateur survient lorsqu’un petit nombre d’immigrants forment une nouvelle population et qu’ainsi les descendants ont une majorité de gènes provenant de ces quelques ancêtres. L’effet fondateur québécois, qui résulte de l’établissement de quelques milliers d’immigrants français aux XVIIe et XVIIIe siècles, est bien documenté. Mais des effets fondateurs régionaux ont aussi été identifiés. Ce mémoire de maîtrise vise à déterminer si un effet fondateur régional est à l’oeuvre dans la région de Lotbinière (Chaudière-Appalaches), dont le peuplement initial remonte à la fin du XVIIe siècle. Le fichier BALSAC et le Registre de la population du Québec ancien ont permis de constituer deux groupes de descendants, 715 individus mariés à la fin du XVIIIe siècle, et 60 autres mariés à la fin du XXe siècle. Par généalogies ascendantes et descendantes, les fondateurs immigrants et régionaux de la région ont par la suite été identifiés. Les résultats indiquent que l’effet fondateur régional avait encore une forte empreinte chez le groupe de descendants du XVIIIe siècle, mais que l’impact s’atténue en ce qui concerne les descendants contemporains. L’homogénéité démontrée par les coefficients d’apparentement et l’indice de contribution génétique uniforme, le petit nombre de fondateurs régionaux et le fait que 65 % des gènes contemporains étaient déjà introduits en 1800 sont des signes qui pointent vers un effet fondateur régional. Par contre, le nonisolement de la région, la proportion modérée de gènes contemporains introduits par les premiers fondateurs régionaux et les niveaux de consanguinité semblables aux autres régions du centre du Québec, incitent à nuancer cette conclusion. En fait, il y a possiblement deux Lotbinière : le Lotbinière ancien, sur la rive et le Lotbinière nouveau, dans les terres; chacun ayant son pool génique et son historique de peuplement propre. / A founder effect occurs when a small number of immigrants form a new population and thus the descendants carry a majority of genes from these few ancestors. Québec’s founder effect, which resulted from the settlement of a few thousand French immigrants during the 17th and 18th centuries, is well documented. But regional founder effects have also been identified. This master’s thesis aims to determine whether a regional founder effect is at work in the Lotbinière region (Chaudière-Appalaches), where the initial settlement goes back to the 17th century. With the BALSAC database and the Registre de la population du Québec ancien, two groups of descendants have been set up: 715 individuals married during the late eighteenth century, and 60 others married during the late twentieth century. By reconstituting ascending and descending genealogies, immigrant founders and regional founders of the area have been identified. The results indicate that the regional founder effect still had a strong footprint among the group of eighteenth century descendants, but that this impact diminishes for the contemporary descendants. The homogeneity demonstrated by kinship coefficients and the founder’s uniform number, the small number of regional founders and the fact that 65 % of contemporary genes were already introduced in 1800 are signs that point to a regional founder effect. However, the nonisolation of the region, the moderate proportion of contemporary genes introduced by the first regional founders and inbreeding levels which are similar to other regions of central Quebec, suggest a less straightforward conclusion. In fact, there are possibly two Lotbinière: the old Lotbinière, on the river bank, and the new Lotbinière, inland, each one having its own gene pool and settlement history.

The objective of the thesis is an analysis, description and subsequent comparison of different aspects in relationships between the founders and the headmasters of primary schools, and subsequently a presentation of possible differences and similarities in these relationships in the Czech Republic and in Slovakia, in both legal and non-legal framework; and a description of the real situation of these relationships more than 20 years after the dissolution of Czechoslovakia. The starting point for the research are relevant legal regulations, such as acts of parliament, delegated legislation and specific legal and other documents concerning founders of private and denominational schools. The Czech and Slovak educational systems had the same development since the foundation of Czechoslovakia in 1918. After the dissolution of Czechoslovak federation the development and changes in Czech and Slovak educational systems had a different, separate development. The relationship between the school founder and its headmaster has significant influence on the school activities and direction. The thesis describes similarities and differences in these relationships in both countries and points out possibilities for mutual inspirations.

過去許多國內外的研究顯示，由創業者所經營之家族企業公司績效表現與投資決策優於由接班者所經營之家族企業和非家族企業。然而，台灣過去卻鮮少有文獻探討創業者與接班者在投資決策上的主要差異，以及是否在特定的公司治理特性下可以協助創業者和接班者做決策，進一步增加公司價值。 本研究主要以2010年至2014年間台灣上市櫃家族企業作為樣本，並將樣本分為由創業者所經營之家族企業與接班者所經營之家族企業，探討由創業者經營之家族企業與接班者所控制之經營企業在併購決策上是否有所不同，在何種公司治理特性或是公司特色可使併購宣告效果增加。本研究以兩階段迴歸和事件研究法作為研究方法，第一部分分析創業者與接班者在公司經營績效上之差異，第二部分分析創業者與接班者在併購宣告效果上的差異，最後進一步分析，何種公司治理特性或是公司特色可使併購宣告之累積異常報酬增加。實證結果顯示，創業者所經營之公司經營績效較佳，且由創業者所作之併購決策，能夠顯著提升併購宣告之累積異常報酬。此外，本研究發現外部董事比例越高，對於投資人預期之累積異常報酬顯著負向效果;然而外部股東持股對於併購宣告之累積異常報酬則有正向之加強效果。 / Past studies indicate that founder-family firms exhibit better firm performance and investment decisions than successor-family firms and non-family firms. However, little research has examined the difference in investment decisions across generations (founders and successors) in Taiwan. Moreover, it is unclear whether there exist some specific firm characteristics or corporate governance structure arrangements that can improve the decision-making of corporate investment to enhance firm value. This study employs the family firms and M&A data during the period of 2010 to 2014 in Taiwan to examine whether M&A decisions differ across family generations in Taiwan. Through the two-stage least squares regression analysis and the event study analysis, we find that the founder-family firms have better firm performance than successor-family firms. The founder-family firms also earn higher acquisition announcement returns than successor-family firms. Besides, we show that the percentage of outside directors has a negative effect on the acquisition announcement returns while the largest outside ownership is positively correlated with the acquisition announcement returns.

La ṣaḥīfa de Médine, a suscité l’attention des érudits occidentaux depuis la deuxième moitié du dix-neuvième siècle,à un tel point que P.L. Rose la considère comme « une struc- ture squelettique » qui contrôle les rapports de la Sīra. Elle a été préservée grâce à deux historiographes du 3ème/9ème siècle : Ibn Hishām et Abū ‘Ubayd ; la recherche contemporaine la place, dans l’ensemble, dans les cinq premières années de l’hégire. Elle illustre clairement, à travers ses variantes présentes et dans le texte lui- même et dans sa chaîne de transmission, les aléas, forcément dommageable,du passage d’une culture de l’oralité à l’écrit. L’accès à l’écrit n’était pas si simple que nous avons toujours cru. Le tournant capital était,lorsque le Barmakide, Ja‘far Ibn Yaḥya (m. 187/803), introduit, vers la fin du 8e/ début du 9e siècle, l’usage du papier dans les bureaux officiels. Cette réforme est due au coût moins élevé de cette matière,et notamment à l’impossibilité de gratter ou laver le papier, à l’inverse du papyrus et du parchemin. Cette Ṣaḥīfa a été fondamentalement produite durant la période prophétique,mais elle a été sans doute modifiée postérieurement,en rajoutant des paragraphes, omettant d’autres, en rajoutant des paragraphes, omettant d’autres, et en particulier en réorgani-sant ces derniers d’une façon qui ne se conforme pas toujours à son classement initial. Ce Texte nous fournit également les connotations originales des grands termes islamiques, comme mu’min et kāfir. / The Ṣaḥīfa of Medina, has drawn the attention of the Western scholars since the second half of the nineteenth century, to such an extent that P. L. Rose considers it as a “skeletal structure’’, which controls the veracity of Sīra-reports. It has been preserved thanks to two historiographers of the 3rd/9thcentury : Ibn Hishām and Abū ‘Ubayd ; the contemporary research situates it, on the whole, in the first five years of Hijra.It clearly illustrates, through its variants present in the text itself as well as in the chain of transmission, the vagaries, necessarily harmful, moving from an oral transmission, culture to a written one. The access to the writing was not so simple that we have always believed. The crucial turning point was when the Barmakid Ja‛far Ibn Yaḥya, (d. 187/803), introduced, by the end of the 8th/ beginning of the9th century, the usage of the paper in the government offices. This reform was due to the ower cost of this material and in parti- cular to the impossibility of scratching or washing paper, unlike papyrus and parchment.This Ṣaḥīfa wasfundamentally produced during the Prophet’s life time, however it was doubtless modified later, adding paragraphs,deleting others, and particularly organizing them in a way thatdoes not always comply with its initial ranking. This Text provides too original connota- tions of great Islamic words,like mu’min and kāfir.

La tesi que teniu a les mans recull quatre treballs amb un objectiu comú; determinar si els patògens (virus, bacteris, paràsits.) han exercit pressions selectives sobre els genomes dels seus hostes (com per exemple els humans).Sabent que la detecció de l'empremta de la selecció permet identificar aquelles regions del genoma que han estat rellevants al llarg de l'evolució d'una espècie, ja que a nivell local és la variació funcional qui acaba essent objecte de la selecció, ens hem disposat a estudiar els possibles senyals de selecció en gens relacionats amb la interacció hoste-patògen. En concret, hem analitzat gens que codifiquen per: a) components del sistema immunitari innat i, b) enzims de glicosilació, la majoria dels quals s'inclouen en quatre de les principals rutes biosintètiques de glicans, en diferents poblacions humanes.Com a conclusió principal; ambdós conjunts de gens mostren clars senyals de selecció. A més hem vist que segons el context biològic on és troben certs gens és veuen més afectats per l'acció de la selecció natural. / The present thesis includes four studies with a common objective: determining whether pathogens (virus, bacteria, parasites.) have exerted selective pressures on the genome of their hosts (for example, humans).Detecting signatures of positive selection is a useful tool to identify functionally relevant genomic regions since selection locally shapes the functional variation. Based on this premise, we have studied the possible signatures of selection in genes related to host-pathogen interactions. Specifically, we have analyzed those genes encoding: a) components of the innate immunity response; and ii) glycosylation enzymes most of them involved in four major glycan biosynthesis pathways, in different human populations.The main conclusion obtained from these studies is that both studied gene categories show clear signatures of selection. Moreover, we have determined that according to their biological context certain genes are more prone to the action of selection.