Metastasis is the main cause of cancer morbidity and mortality. Despite its clinical significance, several fundamental questions about the metastatic process in humans remain unsolved. Does metastasis occur early or late in cancer progression? Do metastases emanate directly from the primary tumor or give rise to each other? How does heterogeneity in the primary tumor relate to the genetic composition of secondary lesions? Addressing these questions in representative patient populations is crucial, but has been difficult so far. Here we present a simple, scalable PCR assay that enables the tracing of tumor lineage in patient tissue specimens. Our methodology relies on somatic variation in highly mutable polyguanine (poly-G) repeats located in non-coding genomic regions. We show that poly-G mutations are present in a variety of human cancers. Using colon carcinoma as an example, we demonstrate an association between patient age at diagnosis and tumor mutational burden, suggesting that poly-G variants accumulate during normal division in colonic stem cells. We further show that poorly differentiated colon carcinomas have fewer mutations than well-differentiated tumors, possibly indicating a shorter mitotic history of the founder cell in these cancers. We collect multiple spatially separated samples from primary carcinomas and their metastases and use poly-G fingerprints to build well-supported phylogenetic trees that illuminate each patient's path of progression. Our results imply that levels of intra-tumor heterogeneity vary significantly among patients.

Pluripotent stem cells have the capacity to develop into different cell lineages and can be manipulated into certain cell types through the use of small molecule inducers. Retinoic acid (RA) signaling through retinoic acid receptors (RAR) and retinoid X receptors (RXR) has the ability to direct lineage determination but has yielded disappointing results in promoting skeletal myogenesis in embryonic stem (ES) cells. RXR is crucial in embryonic development although it is generally considered to act as a silent partner for other nuclear receptors such as RAR. Our findings demonstrate that rexinoid specific signaling enhances skeletal myogenesis and requires β-catenin but not RAR. Moreover, RXR signalling in mouse ES cells can efficiently enhance skeletal myogenesis and closely recapitulates sequential events observed in vivo. Since ES cells closely represent the properties of the developing embryo, efficiently generating skeletal muscle provides a means to further scrutinize signaling pathways in myogenic development in view of developing therapies for muscle related diseases.

The data delivery architectures in most enterprises are complex and under documented. Conceptual business models and business analytics applications are created to provide a simplified, and easy to navigate view of enterprise data for analysts. But the construction of such interfaces is tedious, manually intensive to build, requiring specialized technical expertise, and it is especially difficult to map exactly where data came from in the organization. In this paper we investigate how two aspects (lineage and requests for data i.e. semantics and new reports) can be addressed by tying metadata documentation to a systematic data delivery architecture in order to support business analytics applications. We propose a tool framework that includes a metadata repository for each step in the data delivery architecture, a web based interface to access and manage that repository and mapping tools that capture data lineage to support step by step automation of data delivery.

Originally presented as the author's thesis (Freie Universität Berlin, 2006). / Includes bibliographical references (p. 255-269).

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [79]-97).

No description available.

O presente trabalho teve como objetivo avaliar novilhos resultantes da seleção genética de diferentes linhagens da raça Canchim (5/8 Charolês, 3/8 Zebu), recriados a pasto e terminados em confinamento, em relação ao consumo alimentar, desempenho, emissão de metano entérico, características de carcaça e cortes cárneos. O experimento foi desenvolvido na Empresa Brasileira de Pesquisa Agropecuária, unidade Pecuária Sudeste, São Carlos/SP. Foram utilizados 46 novilhos da raça Canchim (15 meses, 291 kg de peso vivo), 13 pertencentes a linhagem antiga, 20 a linhagem nova e 13 provenientes do acasalamento entre estas linhagens. A linhagem antiga é mantida como rebanho fechado desde 1953 e foi formada com base em 53 touros Charoleses importados da França, já a linhagem nova teve origem a partir de 1990 com a utilização de touros Charoleses de diferentes origens (Argentina, Brasil, Estados Unidos, França, Inglaterra), e a partir de 1998, com o acasalamento entre as duas linhagens formou-se a linhagem cruzada. Durante a recria a pasto (165 dias), os animais foram alojados em uma área de pastagem (Panicum maximum cv. Tanzânia), onde o manejo adotado foi o de pastejo rotacionado com lotação variável, para as medidas de desempenho foram executadas pesagens a cada 33 dias, e a mensuração da emissão de metano entérico através da técnica do gás traçador hexafluoreto de enxofre realizada em 12 animais da linhagem antiga e 12 da nova. No período de terminação em confinamento, os animais foram dispostos em 4 baias e receberam alimentação ad libitum durante 105 dias, o ganho de peso foi medido a cada 28 dias e para a mensuração de emissão de metano os mesmos animais avaliados a pasto, tiveram acesso ao sistema automatizado GreenFeed®. No momento do abate, foram coletadas informações sobre o peso de carcaça quente, e após 24 horas de resfriamento em câmara fria, o peso da carcaça fria, do traseiro especial, dianteiro e ponta de agulha e na desossa os pesos individuais dos cortes cárneos comerciais. A linhagem nova mostrou-se superior a antiga no período de recria nas variáveis de ganho médio diário, conversão e eficiência alimentar, não se diferenciando dos cruzados. Durante a terminação em confinamento, foi observado o mesmo em relação ao ganho médio diário, já em relação ao consumo, a linhagem nova e os cruzados apresentaram maiores ingestões de alimento comparados à linhagem antiga, enquanto a conversão alimentar dos animais cruzados apresentou maior valor comparados às das linhagens. Na recria a pasto, para se obter maiores ganhos de peso, melhor conversão alimentar e eficiência alimentar, devem ser utilizados animais resultantes de processos de seleção genética. A seleção genética para características de desempenho produtivo não garante animais com menores emissões de metano em condições de pastejo. Nos animais em fase de terminação em confinamento, o maior ganho de peso, melhor conversão alimentar e melhor acabamento de carcaça são obtidos através da utilização de animais resultantes de processos de seleção genética. O mesmo tipo de seleção para características de desempenho produtivo em confinamento leva a maiores consumos diários de alimento e consequentemente a maiores emissões de metano diárias. / The objective of this study was to evaluate steers resulting from the genetic selection of different Canchim (5/8 Charolais, 3/8 Zebu) lineages, rearing to pasture and finished in feedlot, in relation to feed intake, performance, enteric methane emission, carcass traits and retail cuts. The experiment was carried out at the Brazilian Agricultural Research Corporation (Embrapa), Southeast Livestock, São Carlos / SP. A total of 46 Canchim steers (15 months, 291 kg live weight) were used, 13 from the ancient lineage, 20 from the new lineage and 13 from the mating between these lineages. The ancient lineage is kept as a closed herd since 1953 and was formed by 53 Charolais bulls imported from France. The new lineage originated from 1990 with the use of Charolais bulls from different origins (Argentina, Brazil, the United States, France, England), and from 1998 the crossed lineage was formed with the mating between the two lineages. During grazing (165 days), the animals were housed in an pasture area (Panicum maximum cv. Tanzania), where the management used was rotational grazing with variable stocking, for the performance measures were performed weighing every 33 days, and the measurement of the enteric methane emission through the sulfur hexafluoride tracer gas technique was performed in 12 animals of the ancient and 12 of the new lineage. In feedlot the animals were housed in 4 pens and fed ad libitum for 105 days. The weight gain was measured every 28 days and as for the measurement of methane emission the same animals evaluated on pasture had access to the GreenFeed® automated system. Information on the hot carcass weight was collected at the time of slaughter and after 24 hours of cooling in the cold chamber, the weights of the cold carcass, of the special hind, fore and spare ribs, and the individual weights of the retail cuts in boning. The new lineage was superior to the ancient one in the rearing period in the variables of average daily gain, conversion and feed efficiency, not differing from the animals crossed. During feedlot, it was observed the same in relation to the average daily gain, already in relation to intake, the new lineage and the crossbreeds presented higher feed intakes compared to the ancient lineage while the feed conversion of the crossed animals presented higher value compared with the new and ancient lineages. In pasture recreating, in order to obtain greater weight gains, better feed conversion and feed efficiency, animals resulting from genetic selection processes must be used. Genetic selection for performance traits does not guarantee animals with lower methane emissions under grazing conditions. For feedlot animals, the highest weight gain, better feed conversion and better carcass finishing are obtained through the use of animals resulting from genetic selection processes. The same type of selection for traits of performance in feedlot leads to higher daily feed intake and consequently to higher daily methane emissions.

Il peut sembler étonnant de consacrer une étude d’ampleur aux fortunes politiques d’une fée médiévale, d’une part parce qu’il est habituel de distinguer merveilleux et politique - alors que le recours au merveilleux est courant pour légitimer un pouvoir ou pour fonder une communauté politique -, et d’autre part parce que la branche maîtresse de la lignée desLusignan, dont Mélusine est l’ancêtre mythique, est éteinte depuis 1308. Pourtant, étonnamment, Mélusine, merveille suscitant des interprétations et représentations contrastées, entre dans des dynamiques politiques multiples. Dès le Moyen Âge, elle incarne des fortunes diverses, l’essor et le déclin de la lignée des Lusignan, qu’elle justifie.Instrumentalisée à des fins de domination, de légitimation et pour célébrer une mémoire lignagère dans les romans médiévaux de Jean d’Arras (1393) et Coudrette (c.1401), Mélusine s’impose au fil des siècles comme la Merlusine, la mère des Lusignan, mais aussi d’autres lignées aristocratiques, par le biais de textes littéraires, paralittéraires etd’armoiries. Parallèlement, dès le Moyen Âge, mais de façon accrue depuis le XXe siècle, cette figure lignagère est défigurée, ses enjeux sont déplacés, et Mélusine peut ainsi informer des questionnements identitaires divers, relatifs à une classe sociale ou à un individu, à la Nation ou à l’affirmation d’idées féministes. / It can seam surprising to dedicate such a consistent study to political sorts of a medieval fairy, on the one hand because it is common to differentiate fantasy and politics — whereas the appeal to fantasy is common to legitimate a power or to build a political community —, and on the other hand because the main branch of the Lusignan lineage, of which Mélusine is the mythical ancestor, has been exctincted since 1308. However, surprisingly, Mélusine, a marvel drawing contrasted understandings and representations, falls into multiple political dynamics. As early as the Middle Age, Mélusine incarnates diverse sorts : the expansion and the decline of the Lusignan lineage that she justifies. Manipulated for domination andlegitimation purposes, as well as to celebrate a lineage memory explored in medieval novels by Jean d’Arras (1393) and Coudrette (c.1401), Mélusine establishes herself over the centuries through literary and paraliterary texts and coats of arms as the Merlusine, the mother of the Lusignan, but also the mother of other aristocratic lineages. At the same time, from the Middle Age onwards, but in an increased way since the 20th century, this lineage figure has been disfigured, its goals have been displaced, and Mélusine can respond to multiple identity questionings related to a social class or an individual, to the Nation or to the assertion of feminist ideas.

The data delivery architectures in most enterprises are complex and under documented. Conceptual business models and business analytics applications are created to provide a simplified, and easy to navigate view of enterprise data for analysts. But the construction of such interfaces is tedious, manually intensive to build, requiring specialized technical expertise, and it is especially difficult to map exactly where data came from in the organization. In this paper we investigate how two aspects (lineage and requests for data i.e. semantics and new reports) can be addressed by tying metadata documentation to a systematic data delivery architecture in order to support business analytics applications. We propose a tool framework that includes a metadata repository for each step in the data delivery architecture, a web based interface to access and manage that repository and mapping tools that capture data lineage to support step by step automation of data delivery.

Pluripotent stem cells have the capacity to develop into different cell lineages and can be manipulated into certain cell types through the use of small molecule inducers. Retinoic acid (RA) signaling through retinoic acid receptors (RAR) and retinoid X receptors (RXR) has the ability to direct lineage determination but has yielded disappointing results in promoting skeletal myogenesis in embryonic stem (ES) cells. RXR is crucial in embryonic development although it is generally considered to act as a silent partner for other nuclear receptors such as RAR. Our findings demonstrate that rexinoid specific signaling enhances skeletal myogenesis and requires β-catenin but not RAR. Moreover, RXR signalling in mouse ES cells can efficiently enhance skeletal myogenesis and closely recapitulates sequential events observed in vivo. Since ES cells closely represent the properties of the developing embryo, efficiently generating skeletal muscle provides a means to further scrutinize signaling pathways in myogenic development in view of developing therapies for muscle related diseases.