Abstract In the present study, mutations in BRCA1 and BRCA2, the two major genes predisposing individuals to hereditary breast and ovarian cancer, were screened in Finnish and Turkish cancer families. Germline BRCA1 mutations were found in 7% (6/88) and BRCA2 mutations in 6% (5/88) of the Finnish families studied in Oulu. Two distinct BRCA1 (3745delT, 4216nt-2A→G) and three BRCA2 (999delTCAAA, 6503delTT, 9346nt-2A→G) mutations were identified, all of which are recurrently found in Finland. In the 15 Turkish cancer families studied, 5382insC and 5622C→T were detected in BRCA1, and 3414delTCAG in BRCA2. The novel 3414del4 mutation was found in a family with a case of male breast cancer. In order to determine their ages and origin, 9 recurrent Finnish BRCA1 and BRCA2 mutations were studied further as regards haplotype conservation. Common origins approximately 18–80 generations (400–1600 years) ago were demonstrated for all studied mutations by partial haplotype sharing. The majority of the mutations showed geographical clustering, supporting the theory of regional founder effects. Four of the nine mutations are unique for Finland, whereas five have also been seen elsewhere. Mutations in the 5' end of BRCA1 tend to predispose individuals to ovarian cancer and those found in the 3' end to breast cancer. The age of ovarian cancer onset was significantly lower for BRCA1 (51 years) than for BRCA2 mutation carriers (61 years). Germline TP53 mutations were sought in the Finnish breast cancer families found to be negative after BRCA1 and BRCA2 screening but who exhibited some phenotypic features of the Li-Fraumeni syndrome. The Asn235Ser was found in a family displaying Li-Fraumeni syndrome phenotype and the Tyr220Cys in a family with a milder Li-Fraumeni-like phenotype. The nature of both mutations as cancer-predisposing alterations was supported by means of loss of heterozygosity (LOH) and p53 immunohistochemistry studies. Regional clustering of BRCA1 and BRCA2 founder mutations enables targeted genetic tests including especially those mutations characteristic of the birthplace of each patient. Additional genes are likely to explain a large proportion of the inherited susceptibility to breast cancer in particular. Germline TP53 mutations are expected to be found in the breast cancer families with other clinical features seen in the Li-Fraumeni syndrome.

Yes / We integrate the institutional perspective with research on the governance role of private equity firms in an investigation of Founder-CEO successions in Initial Public Offerings (IPOs) in emerging markets. Using a unique, hand-collected and comprehensive sample of 191 firms having undertaken IPOs in 21 markets across the African continent between January 2000 and August 2016, we apply instrumental variable (IV) Probit methodology and find that higher levels of private equity ownership are positively associated with the probability of the founder's retention as CEO, especially in the context of low-quality formal institutions. Further, in societies with high tribalism, higher private equity ownership is associated with an increased likelihood of founder retention. Voids in the institutional architecture underscore the importance of the founder as a key organizational resource for the firm and a source of institutionalized legitimacy, which in turn confers on the firm an ability to access required resources.

5 TITLE: Evaluation of directors of elementary schools and kindergartens from the perspective of municipal founders in the Pilsen region and determination of evaluation criteria. AUTHOR: Miroslava Chottová DEPARTMENT: Centre for Education Management SUPERVISOR: Doc. Jaroslav Kalous, Ph.D. ABSTRACT: The main subject of this dissertation is process of evaluation of directors at elementary schools and kindergartens by municipal founders in region of Pilsen and matters related to it. The content is based on specialized literature, results of questionnaire research done with the municipal founders and also the directors of elementary schools and kindergartens, and practical experience. The partial objective of this work is to confirm or alternatively disprove hypotheses regarding the evaluation of the directors at elementary schools and kindergartens by municipal founders (evaluation according to criteria, evaluation as a motivational factor), based on mapping the methods of assessment of the directors and the criteria currently applied by the founders. The main objective of this work is to process a sample for methodical evaluating procedure including a sample set of evaluating criteria, based on findings in the specialized literature and questionnaire research, and own experience. The methodical procedure...

Purpose – The purpose of this project was to extrapolate knowledge of successful leadership practices, determine what led to and nurtured what became an integrated organizational culture and identify any decisions and/or transformational events that re-defined Moffitt Cancer Center’s (MCC) course or helped propel it to levels far beyond what was originally imagined. The aims of this study were discovery of the foundational factors and events that significantly impacted the creation, growth and evolution of the center, making MCC an institution of transformational change that had achieved state and national prominence. Design – This was an exploratory study guided by a qualitative phenomenological research methodology using an interpretivist approach. Data was derived from twenty one-on-one interviews with people who had the specific knowledge and expertise necessary to obtain a better understanding of the leadership, culture and transformational events that transformed MCC into the institution that it is today. Interviewees included former and current MCC executive leaders, board members and key program directors, as well as the founder and two other former Speakers of the Florida House of Representatives. A literature review was conducted to explore founders, visionary leadership, organizational culture, and transformational organizations. Findings – Key findings included discovery of the factors and events that impacted MCC’s growth and success. The interview process revealed three foundational factors pertaining to visionary leadership qualities of the founder and others, a mission-based culture and four transformational events that set MCC on a course of independence and self-governance. The literature review, with an emphasis on founders, visionary leadership, culture and transformational institutions, revealed useful information to draw comparisons and differences in the historical context of MCC’s growth and impact. Value – MCC, created in Florida statute, existed as a private not-for-profit entity that, statutorily, served as an instrumentality of the state. As such, it had an interestingly distinct role as a hybrid organization that served a public and private sector need; while, very specifically, serving the cancer research and care needs of patients throughout the state and beyond. While the previously mentioned business literary research works are plentiful in the private and public sectors, a gap exists for hybrid organizations such as MCC. Future research could focus on organization founders who did not become part of the executive leadership structure.

Doctor of Philosophy(PhD), / Until recently, Northwestern Australia was thought to be relatively free of serious fruit fly pests. Although a noxious strain, present in Darwin since 1985, was widely believed to be an infestation of the Queensland fruit fly, Bactrocera tryoni, from the East coast, the fruit flies present outside this area were believed to be the benign endemic species, B. aquilonis. However, during the year 2000, infestations of fruit flies were discovered on major commercial crops in both Western Australia and the Northern Territory. It was not known whether these outbreaks were due to an invasion of the major pest species, Bactrocera tryoni, a change in the behaviour of B. aquilonis, or a hybridisation event between the two species. Finding the source of these outbreaks has been complicated by the fact that, since B. tryoni and B. aquilonis are virtually indistinguishable morphologically, it was not known which species are present in the region. Traditionally any tryoni complex fly caught in the Northwest was called B. aquilonis based solely on location. In order to get a good population profile of the region, an extensive trapping program was set up to include flies from urban areas, commercial crops and natural areas where the benign strain is thought to remain. Tests of genetic differentiation and clustering analyses revealed a high degree of homogeneity in the Northwest samples, suggesting that just one species is present in the region. The Northwest samples were genetically differentiated from the Queensland samples but only to a small degree (FST =0.0153). MtDNA sequencing results also showed a small degree of differentiation between these regions. A morphological study of wing shape indicated that there are some minor identifiable morphological differences between East coast and Northwest laboratory reared flies. This difference was greater than that seen between B. jarvisi populations across the same geographic range. The results suggest that the flies caught in the Northwest are a separate population of B. tryoni. Soon after pest flies were discovered in Darwin, a population became established in Alice Springs. This population had a low genetic diversity compared with Queensland and Darwin populations, and showed evidence of being heavily founded. In 2000, an outbreak was discovered in the nearby town of Ti Tree. Due to the geographic and genetic similarity of these populations, Alice Springs was determined to be the source of the Ti Tree outbreak. To investigate the founding of these populations, a program was developed to estimate the propagule size. Using a simulation method seven different statistics were tested for estimating the propagule size of an outbreak population. For outbreaks originating from populations with high genetic diversity, the number of alleles was a good estimator of propagule size. When, however, the genetic diversity of the source population was already reduced, allele frequency measures, particularly the likelihood of obtaining the outbreak population from the source population, gave more accurate estimates. Applying this information to the Alice Springs samples, it was estimated that just five flies were needed to found the major population in and around Alice Springs. For Ti Tree, the propagule size was estimated to be 27 flies (minimum 10). In 2000, a much larger outbreak occurred in the developing horticultural region of Kununurra in northern Western Australia. An important question for the management of the problem is whether there is an established fly population or the flies are reinvading each year. This population was found to have a large amount of gene flow from the Northern Territory. Within the Kununurra samples, one group of flies was genetically differentiated from all the other samples. This group came from a small geographic area on the periphery of Kununurra and appeared to be the result of an invasion into this area at the time when the population was building up following the dry season. A further threat to the Northwest horticultural regions comes from B. jarvisi. A recent increase in the host range of this species has lead to speculation that it may become a greater pest in Northwestern Australia. At the present time, protocols for the population monitoring and disinfestation of this species are not in place. Here it is shown that B. jarvisi eggs are more heat tolerant than B. tryoni eggs and that monitoring of B. jarvisi populations is possible using cue lure traps placed according to fruiting time and location of their favoured host, Planchonia careya.

Family businesses have been a majority in the stage of world economy, and whose combination of ownership, management and family make relevant management issues even more complex. The significance and complexity of family businesses have incrementally attracted more scholar attention. Literature indicates that only one-thirds of family businesses can be passed on to second generation. Succession, therefore, becomes an important issue in the continuity of family business. This study, in adoption of qualitative approach, aims at exploring how the attitude of founders in the family business towards succession can influence the succession process and how they adjust roles in the business during the succession process, and the importance of successors¡¦ level of interests, abilities and development and the criteria of successor selection. Four case companies were interviewed. The results are as follows: 1). Founders in the family business usually nominate their desired successors, but do not have further succession plan, and moreover, remain their influences or statues in the business as consultants once they retire or transfer leadership. 2). Preferences in male siblings are demonstrated. 3). In terms of training and development, successors rely on on-the-job trainings and founders to pass their connections and relevant industrial knowledge, by that successors are likely to build up their legitimacy and gain trust from stakeholders. 4). Successors¡¦ personal interests that are accommodated by succeeding the business is positive for succession. 5). The value of family in the Chinese context is positive for succession.

Doctor of Philosophy(PhD), / Until recently, Northwestern Australia was thought to be relatively free of serious fruit fly pests. Although a noxious strain, present in Darwin since 1985, was widely believed to be an infestation of the Queensland fruit fly, Bactrocera tryoni, from the East coast, the fruit flies present outside this area were believed to be the benign endemic species, B. aquilonis. However, during the year 2000, infestations of fruit flies were discovered on major commercial crops in both Western Australia and the Northern Territory. It was not known whether these outbreaks were due to an invasion of the major pest species, Bactrocera tryoni, a change in the behaviour of B. aquilonis, or a hybridisation event between the two species. Finding the source of these outbreaks has been complicated by the fact that, since B. tryoni and B. aquilonis are virtually indistinguishable morphologically, it was not known which species are present in the region. Traditionally any tryoni complex fly caught in the Northwest was called B. aquilonis based solely on location. In order to get a good population profile of the region, an extensive trapping program was set up to include flies from urban areas, commercial crops and natural areas where the benign strain is thought to remain. Tests of genetic differentiation and clustering analyses revealed a high degree of homogeneity in the Northwest samples, suggesting that just one species is present in the region. The Northwest samples were genetically differentiated from the Queensland samples but only to a small degree (FST =0.0153). MtDNA sequencing results also showed a small degree of differentiation between these regions. A morphological study of wing shape indicated that there are some minor identifiable morphological differences between East coast and Northwest laboratory reared flies. This difference was greater than that seen between B. jarvisi populations across the same geographic range. The results suggest that the flies caught in the Northwest are a separate population of B. tryoni. Soon after pest flies were discovered in Darwin, a population became established in Alice Springs. This population had a low genetic diversity compared with Queensland and Darwin populations, and showed evidence of being heavily founded. In 2000, an outbreak was discovered in the nearby town of Ti Tree. Due to the geographic and genetic similarity of these populations, Alice Springs was determined to be the source of the Ti Tree outbreak. To investigate the founding of these populations, a program was developed to estimate the propagule size. Using a simulation method seven different statistics were tested for estimating the propagule size of an outbreak population. For outbreaks originating from populations with high genetic diversity, the number of alleles was a good estimator of propagule size. When, however, the genetic diversity of the source population was already reduced, allele frequency measures, particularly the likelihood of obtaining the outbreak population from the source population, gave more accurate estimates. Applying this information to the Alice Springs samples, it was estimated that just five flies were needed to found the major population in and around Alice Springs. For Ti Tree, the propagule size was estimated to be 27 flies (minimum 10). In 2000, a much larger outbreak occurred in the developing horticultural region of Kununurra in northern Western Australia. An important question for the management of the problem is whether there is an established fly population or the flies are reinvading each year. This population was found to have a large amount of gene flow from the Northern Territory. Within the Kununurra samples, one group of flies was genetically differentiated from all the other samples. This group came from a small geographic area on the periphery of Kununurra and appeared to be the result of an invasion into this area at the time when the population was building up following the dry season. A further threat to the Northwest horticultural regions comes from B. jarvisi. A recent increase in the host range of this species has lead to speculation that it may become a greater pest in Northwestern Australia. At the present time, protocols for the population monitoring and disinfestation of this species are not in place. Here it is shown that B. jarvisi eggs are more heat tolerant than B. tryoni eggs and that monitoring of B. jarvisi populations is possible using cue lure traps placed according to fruiting time and location of their favoured host, Planchonia careya.

The Diploma thesis dealing with the relation between a founder and a director of pre-school education management in the Pilsen region, aims to evaluate a system of kindergartens, which are independent contributory organizations and whose founder is a municipality. To find out what competences the founder has in relation to a kindergarten, in which spheres the founder cooperates with a director. How the founder evaluates director's work, if he does control activities and if he works with outputs of the control bodies, especially the Czech School Inspectorate.To find out what the competences of a kindergarten director are, whether he is supported by the founder or not. To find out how the cooperation between the founders and the directors of kindergartens is evaluated by inspectors of the Czech School Inspectorate who are specialized in pre-primary education and work in the Pilsen Inspectorate of the ČSI. The theoretical part of the thesis is based on the specialized literature, legal regulations and strategic documents concerning kindergartens, their founders and the Czech School Inspectorate in the field of pre-primary education, which were valid at the time of this diploma thesis. The practical part is drawn up on the basis of the results of the survey carried out by the directors of...

Abstract Fragile X syndrome, the most common inherited form of mental retardation syndrome, is caused by an expansion of the CGG trinucleotide repeat in the 5' UTR of the FMR1 gene, with concurrent hypermethylation of the region, which represses FMR1 expression. The syndrome is associated with the folate-sensitive chromosomal fragile site at Xq27.3 (FRAXA), where the gene responsible for the syndrome was first localized by linkage analysis using RFLP markers. In this study the linkage relationships of the RFLP markersat Xq27-28 and the characteristics of the CGG repeat expansion were investigated in northern Finnish fragile X families and molecular diagnostic methods were applied in order to improve diagnosis of the syndrome. Furthermore, the origin of fragile X mutations in the northern part of Finland was studied by haplotype analysis. Linkage studies were performed in 34 northern Finnish fragile X families/pedigrees using a total of 15 RFLPs (defining 11 loci). A refined genetic map around FRAXA including five RFLP markers having recombination fractions of 0.04 or less with FRAXA was obtained in an international study of 112 affected families, containing linkage data on twelve northern Finnish families. Linkage analysis significantly improved carrier detection in fragile X families compared with previous cytogenetic methods used in diagnosis. The most efficient RFLP-based protocol for carrier detection was proposed, which is based on use of the most adjacent markers and a minimum number of restriction enzymes. CGG repeat expansion of the FMR1 gene was investigated in original families collected for linkage studies and additional new ones. Large CGG repeat expansions (Δ > 500 bp) with concomitant methylation of the adjacent CpG island, i.e. full mutations, were found to be associated with mental retardation completely in males, but only 50% of the females having a full mutation were mentally impaired. Premutations (Δ < 700 bp) were found in healthy carriers. There was a size range of Δ = 500 to 700 bp, where the expansions could be either abnormally methylated or non-methylated, and it appeared that methylation is more important in determining the phenotype than the exact size of an expansion. Instability of the enlarged CGG repeats was detected, leading preferentially to size increases in successive generations. The instability of premutations was found to be stronger and the size increases larger in maternal than in paternal transmissions, and transition to a full mutation occurred only in female transmissions. In addition, the size of a maternal premutation was shown to have an important influence on the risk of its transition to a full mutation when transmitted. The critical premutation size leading invariably to full mutation in the offspring was found to be between Δ = 175 to 200 bp. In one of the studied families a rare contraction of a paternal premutation to a normal CGG repeat number in one of the daughters and further in her son was detected. Direct mutation analysis including measurement of the CGG repeat size and hypermethylation allowed unambiguous diagnosis of carriers and affected individuals in most cases. Haplotype analysis using two tightly linked microsatellite markers flanking the CGG repeat mutation was performed in 60 unrelated northern and eastern Finnish fragile X families. A significant difference was found in allelic and haplotypic distributions between normal X and fragile X chromosomes. A single haplotype, which was present only in 8% of the normal X chromosomes, accounted for 80% of the fragile X chromosomes. This enrichment of one fra(X) mutation in the Finnish population suggests founder effect.

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13020号 / 論農博第2830号 / 新制||農||1042(附属図書館) / 学位論文||H28||N4966(農学部図書室) / 32948 / (主査)教授 祝前 博明, 教授 今井 裕, 教授 廣岡 博之 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM