Graduation date: 1997

Breast cancer is the most common cancer in women worldwide. However, the genetic alterations that lead to breast cancer are not fully understood. This thesis aims to identify novel genes of potential mechanistic, diagnostic or therapeutic interest in breast cancers by mutational analysis and whole-genome sequencing. In paper I, sequencing of 36 previously identified candidate genes in 96 breast tumors with patient-matched normal DNA determined the somatic mutation prevalence of these candidate genes and identified additional mutations in Notch, NF-κB, PI3K, and Hedgehog pathways as well as in processes mediating DNA methylation, RNA processing and calcium signaling. In paper II, comparison of massively parallel mate-pair sequencing results of a human genome before and after phi29-mediated multiple displacement amplification (MDA) revealed that MDA introduces structural alteration artifacts, with an emphasis on false positive inversions, and impairs the sensitivity to detect true inversions. Therefore, MDA has limited value in sample preparation for whole-genome sequencing for structural alteration detection. In paper III, massively parallel paired-end sequencing identified gene rearrangements in 15 hormone receptor negative breast cancers. Forty validated rearrangements were predicted to directly affect 30 genes, involved in epigenetic regulation, cell mitosis, signalling transduction and glycolytic flux. RNA interference-based assays revealed the potential roles in cell growth of some affected genes, among which DDX10 was implicated to be involved in apoptosis. In paper IV, a method for statistical evaluation of putative translocations detected by massively parallel paired-end sequencing was proposed. In an application of this method to analyse translocations detected by cancer genome deep paired-end sequencing, 76 putative translocations were classified into four categories, with the majority likely to be caused by mismapping due to repetitive regions. Taken together, this thesis provides insights into genes and pathways mutated in sporadic breast cancer genomes, which broaden our understanding of the genetic basis of breast cancer and may ultimately facilitate the diagnosis and treatment of this disease.

Mémoire (M.Sc.T)-- Université du Québec à Chicoutimi 1986. / "Mémoire présenté en vue de l'obtention du diplôme de M.Sc.A. (sciences de la terre)" CaQCU Document électronique également accessible en format PDF. CaQCU

Typescript. Includes vita and abstract. Includes bibliographical references (leaves 155-177). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.

Nesse estudo é relatada a descoberta de um grande número de gossans na província vulcânica Paraná, América do Sul, com base em observações de imagens de satélite e trabalho de campo associado à geoquímica e geofísica. Define-se, portanto um novo guia prospectivo para depósitos de ágata e ametista. A área de estudo está localizada na fronteira entre Brasil e Uruguai, e abrange o distrito mineiro de Quaraí e o distrito gemológico de Los Catalanes. Anomalias em imgens de satélite do Google Earth foram identificadas em pelo menos seis minas no distrito gemológico de Los Catalanes, caracterizado nos pampas da região como estruturas irregulares de cor verde intenso e por vezes com textura rugosa marrom. As anomalias ocorrem em vários níveis estratigráficos na sequência vulcânica, sendo denominadas gossans. Três seções cintilométricas realizadas sobre a mina Maurício, no distrito gemológico de Los Catalanes indicam taxas baixas emissões perto de 55 cps (DP = 4,7) no gossan em comparação com a média regional da colada Cordilheira (63 cps). Análises geoquímicas de rocha total de três amostras coletadas na mina indicam elevada perda ao fogo (4,5, 3,4, 4,5 peso%). Conteúdos de perda ao fogo acima de 2 peso% são considerados um forte indicador de alteração hidrotermal. No distrito mineiro de Quaraí, gossans foram estudados em cinco áreas, distribuídas entre as coladas Catalán, Cordillera e Muralha. Os depósitos de classe mundial de geodos de ametista e ágata estão nas coladas Catalán e Cordillera. Anomalias radiométricas negativas (superior a um desvio-padrão) ocorrem nesses gossans. O estudo detalhado de um gossan incluiu uma malha geofísica de 50 x 50 m (K, U, Th e taxa de emissão total) e análises geoquímicas de rocha total (ACME, Canadá). As análises geoquímicas de rocha total de 20 amostras coletadas dentro e fora do gossan classificam as rochas como andesitos basálticos, baixo-Ti, do tipo químico Gramado. As amostras dentro do gossan apresentam valores elevados de perda ao fogo (2,3, 2,8, 2,9, 2,8, 2,9, 2,4, 2,6, 2,6, 2,3 e 2,3 peso%), Enquanto fora do gossan os valores são mais baixos (0,8, 2,3, 0,5, 0,5, 1,6, 0,5, 0,6, 0,9, 1.3, 1,9 peso%). SiO2, K2O e Rb mostram correlação negativa forte com a perda ao fogo, enquanto o MgO tem um leve enriquecimento. A baixa cintilometria no gossan é definida principalmente pelo baixo K2O da rocha alterada. É relatado, portanto, a descoberta de gossans acima geodos de ametista nos depósitos de classe mundial da província vulcânica do Paraná e é apresentada uma primeira descrição da estrutura, um guia prospectivo para depósitos se adiciona. / We report the discovery of a large number of gossans in the intraplate Paraná volcanic province, South America, based on observations of satellite images and field work associated with rock geochemistry and geophysics. We thus define a straitforward propecting guide for agate and amethyst deposits. The study area is located on the border between Brazil and Uruguay, covering the Quaraí mining district and the Los Catalanes gemological district. Anomalies in Google Earth satellite images were identified above six mines in the Los Catalanes gemological district, characterized in the pampas of the region as irregular structures of intense green color and sometimes with brownish, rough texture. The vegetation, scintillometric and geochemical anomalies occur at several stratigraphic levels in the volcanic group. Three scintillometric sections performed on the Maurício mine in the Los Catalanes gemological district indicate low emission rates near 55 cps (sd = 4.7) in the gossan compared with the regional average of colada Cordillera (63 cps). Whole rock geochemical analyses of three samples collected within the underground mine indicate high loss on ignition (4.5, 3.4, 4.5 wt.%). LOI higher than 2% is considered a strong indicator of intense hydrothermal alteration in the gossan. In the Quaraí mining district, gossans were studied in five areas, two in colada Catalán, two in colada Muralha, and one in colada Cordillera. The world-class deposits of amethyst and agate geodes are in coladas Catalán and Cordillera. Negative radiometric anomalies (higher than one standard deviation) occur in these gossans. The detailed study of one gossan included a geophysical grid spacing of 50 x 50 m (K, U, Th and total emission rate) and whole rock geochemical analyses (ACME, Canadá). The whole rock geochemical analyses of 20 samples collected within and outside the gossan classify the rocks as basaltic andesites, low–Ti, Gramado chemical type. The samples inside the gossan display high values of loss on ignition (2.3, 2.8, 2.9, 2.8, 2.9, 2.4, 2.6, 2.6, 2.3 and 2.3 wt.%), while outside the gossan the values are lower (0.8, 2.3, 0.5, 0.5, 1.6, 0.5, 0.6, 0.7, 1.1, 1.3 and 1.9 wt.%). SiO2, K2O and Rb show strong negative correlation with loss on ignition, while MgO has a slight enrichment. The low scintillometry in the gossan is defined primarily by the lower K2O of the altered rock. We thus report the discovery of gossans above amethyst geodes in the world-class deposits of the Paraná volcanic province and present a first description of the structure, a straitforward prospecting guide for additional deposits.

Les chondrites carbonées de type 1 et 2 comprennent les météorites les plus primitives d’un point de vue chimique et pétrologique. Ce caractère primitif est associé à l’abondance de matière organique qui est une phase privilégiée pour l’étude des phénomènes concernant l’héritage du matériel présolaire et sa transformation dans la nébuleuse puis sur les premiers corps. L’objet de cette thèse est l’étude de l’influence des processus post-accrétionnels sur les caractéristiques moléculaires de la matière organique et en particulier la mesure des effets d’oxydation dus à l’altération aqueuse. Nous avons mené une étude comparative basée sur la structure carbonée et l’analyse des fonctions oxygénées et soufrées d’une dizaine de météorites dont les histoires géologiques ont été déterminées par ailleurs. Le degré d’oxydation du soufre, hétéroatome mineur dans la fraction insoluble, a été mesuré par micro-spectrométrie SK-Xanes. La spectroscopie FT-IR a permis la description des structures fines des chaines carbonées et des fonctions riches en oxygène, hétéroatome majeur. La spectrométrie de masse à très haute résolution Orbitrap a été utilisée pour décrire la diversité hétéroatomique des molécules solubles de la chondrite Renazzo (CR2). Les chaines carbonées des chondrites de classe CI et Murchison se différencient de celle des autres météorites par une abondance en groupements terminaux méthyles à la fois supérieure et invariable. Les chondrites de type 1 sont les seules porteuses de fonctions soufrées oxydées acides alors que la spéciation du soufre dans les chondrites de type 2 est invariable. De la même façon, et cette fois pour l’ensemble des chondrites étudiées, les groupements carbonyles sont majoritairement dans les fonctions cétones, en proportion indépendante du degré d’altération aqueuse. Tous les paramètres mesurés dans cette étude nous poussent à conclure que la variabilité moléculaire au sein des chondrites carbonées de type 1 et 2 trouve moins son origine dans l’empreinte de l’hydrothermalisme que dans une hétérogénéité du précurseur organique accrété par chaque corps parent. En particulier, nos mesures invalident l’hypothèse selon laquelle l’altération serait à l’origine d’une conversion oxydative des chaines carbonées en fonctions acides carboxyliques. / Type 1 and 2 carbonaceous chondrites include the most chemically and petrologically pristine meteorites. This intactness goes along with the abundance of organic matter which is a phase of choice to investigate the presolar material processing in the nebula and then on the first bodies. The purpose of this thesis is to study the influence of post-accretional processes on the molecular characteristics of organic matter and in particular the extent of oxidation effects due to aqueous alteration. We have carried out a comparative study based on the carbon structure and functional analysis of more than ten meteorites whose geologic histories were independently determined. The redox degree of sulfur in the insoluble fraction was measured by SK-Xanes spectroscopy. FT-IR spectroscopy gave access to the fine structures of aliphatic chains and oxygen-rich functions. Orbitrap very high resolution mass spectrometry was used to describe the heteroatomic diversity of soluble molecules in the Renazzo (CR2) chondrite. The aliphatic chains of CI chondrites and Murchison differ from others by a higher and unchanging abundance of methyl groups. Type 1 chondrites are the only carriers of oxidized sulfur functions whereas the sulfur speciation in type 2 chondrites is invariable. For all studied chondrites, the carbonyl groups are mainly under the form of ketones and their abundance can’t be related to the degree of aqueous alteration. Any parameters we have measured in this study lead us to conclude that the molecular variability among type 1 and 2 carbonaceous chondrites are less due to the footprint left by the hydrothermal activity than due to the heterogeneity of an organic precursor accreted by each parent body. In particular, our measurements invalidate the hypothesis that the alteration would cause an oxidative conversion of aliphatic chains to carboxylic acid functions.

This thesis deals with alteration: diminutives and augmentatives in contemporary Italian, and their pragmatic functions. The aim of this thesis is to create a list of diminutives and augmentatives used in Italian fiction. The analysis of expressions is based on the texts contained in InterCorp. The starting point is a theoretical introduction to the word formation with special attention to alterative suffixes in Italian and Czech language, with a partial comparison to Spanish. The thesis also concentrates on hypocorisms, phonological and suffixal restrictions, and lexicalization of alteratives. An integral part is the chapter dedicated to pragmatics, speech acts theory and pragmatic use of alterative suffixes. The results of this thesis represent concrete illustrations for various communication situations documented from corpus.

A região das Minas do Camaquã é parte constituinte da Bacia do Camaquã, a qual possui direção NE-NW e é preenchida por sedimentos siliciclásticos intercalados com rochas vulcânicas. A clorita é o argilomineral mais abundante na área, ocorrendo em grande quantidade nos halos de alteração hidrotermal presentes nas rochas encaixantes das mineralizações. O presente trabalho consiste na caracterização petrológica, química e estrutural das cloritas, que fornecem importantes informações sobre diferentes processos e condições de formação do ambiente hidrotermal. Para isso se realizou petrografia óptica, difratometria de raios X, modelamento dos difratogramas através do programa Reynolds Newmod©, e microscopia eletrônica de varredura em amostras representativas de diferentes zonas de alteração hidrotermal identificadas. As cloritas se apresentam com três diferentes tendências: A Clorita I ocorre com aspecto pervasivo sobre a matriz das rochas localizadas próximo aos filões mineralizados. É classificada como Fe-clinocloro, apresenta na fração <1μm predominância do polítipo IIb e um enriquecimento em Mg2+ e na fração <10μm predominância do politipo Ib (900) e enriquecimento em Fe2+; a Clorita II ocorre como veios preenchendo pequenas fraturas. É classificada como Chamosita e apresenta polítipo estrutural IIb; e a Clorita III ocorre alterando minerais detríticos sendo classificada como Mg-chamosita. A variação na quantidade de ferro das cloritas geradas por processos hidrotermais (Clorita I <10 μm e clorita II) fornecem indícios da ocorrência de pelo menos dois pulsos no processo de alteração hidrotermal: um responsável pela intensa alteração da matriz e dos clastos das rochas e outro responsável pela geração dos veios tardios. A variação na quantidade de Fe2+ dos dois diferentes fluidos responsáveis pela cristalização das cloritas fica evidenciada pela associação de co-geneticidade da Clorita II com a hematita, mostrando que o fluido final foi muito mais enriquecido em ferro que o fluido precoce que cristalizou a Clorita I <10 μm. / The region of the Camaquã Mines is a constitutional part of the Camaquã Basin and is accomplished by silliciclastics sediments intercalated with volcanic rocks. Chlorite is the most abundant clay mineral, occurring in great amounts on the hydrothermal alteration halos present in the host rocks of mineralizations. This work consists on the petrologic, chemical and structural characterization of chlorites, which provide important information about different processes and formation conditions of the hydrothermal environment. It was made optical petrography, X ray diffraction, difractograms modeling, and scanning electron microscopy in representative samples of the different hydrothermal alteration zones identified. The chlorites are presented in three different trends: The Chlorite I occurs with pervasive aspect in the hydrothermal alteration halos. It is classified as Fe-clinoclore, and presents in the fraction <1μm the predominance of polytype IIb and an enrichment in Mg2+ and in the fraction <10μm the predominance of the polytype Ib (900) and enrichment in Fe2+; The Chlorite II occurs as veins filling small fractures. It is classified as Chamosite and presents structural polytype IIb; and the Chlorite III occurs altering detritic minerals is classified as Mg-chamosite. The variation on the amount of Fe2+ of the chlorites generated by hydrothermal processes (Chlorite I < 10 μm and Chlorite II) provides indications of the occurrence of at least two pulses on the hydrothermal alteration process: one responsible for the intense alteration of the matrix and clasts of the rocks and the other responsible for the generation of the late veins. This variation on the amount of Fe2+ is evidenced by the co-geneticity association of the Chlorite II with the hematite, showing that the final fluid was much more enriched in iron than the early fluid that crystallized the Chlorite I < 10 μm.

Nesse estudo é relatada a descoberta de um grande número de gossans na província vulcânica Paraná, América do Sul, com base em observações de imagens de satélite e trabalho de campo associado à geoquímica e geofísica. Define-se, portanto um novo guia prospectivo para depósitos de ágata e ametista. A área de estudo está localizada na fronteira entre Brasil e Uruguai, e abrange o distrito mineiro de Quaraí e o distrito gemológico de Los Catalanes. Anomalias em imgens de satélite do Google Earth foram identificadas em pelo menos seis minas no distrito gemológico de Los Catalanes, caracterizado nos pampas da região como estruturas irregulares de cor verde intenso e por vezes com textura rugosa marrom. As anomalias ocorrem em vários níveis estratigráficos na sequência vulcânica, sendo denominadas gossans. Três seções cintilométricas realizadas sobre a mina Maurício, no distrito gemológico de Los Catalanes indicam taxas baixas emissões perto de 55 cps (DP = 4,7) no gossan em comparação com a média regional da colada Cordilheira (63 cps). Análises geoquímicas de rocha total de três amostras coletadas na mina indicam elevada perda ao fogo (4,5, 3,4, 4,5 peso%). Conteúdos de perda ao fogo acima de 2 peso% são considerados um forte indicador de alteração hidrotermal. No distrito mineiro de Quaraí, gossans foram estudados em cinco áreas, distribuídas entre as coladas Catalán, Cordillera e Muralha. Os depósitos de classe mundial de geodos de ametista e ágata estão nas coladas Catalán e Cordillera. Anomalias radiométricas negativas (superior a um desvio-padrão) ocorrem nesses gossans. O estudo detalhado de um gossan incluiu uma malha geofísica de 50 x 50 m (K, U, Th e taxa de emissão total) e análises geoquímicas de rocha total (ACME, Canadá). As análises geoquímicas de rocha total de 20 amostras coletadas dentro e fora do gossan classificam as rochas como andesitos basálticos, baixo-Ti, do tipo químico Gramado. As amostras dentro do gossan apresentam valores elevados de perda ao fogo (2,3, 2,8, 2,9, 2,8, 2,9, 2,4, 2,6, 2,6, 2,3 e 2,3 peso%), Enquanto fora do gossan os valores são mais baixos (0,8, 2,3, 0,5, 0,5, 1,6, 0,5, 0,6, 0,9, 1.3, 1,9 peso%). SiO2, K2O e Rb mostram correlação negativa forte com a perda ao fogo, enquanto o MgO tem um leve enriquecimento. A baixa cintilometria no gossan é definida principalmente pelo baixo K2O da rocha alterada. É relatado, portanto, a descoberta de gossans acima geodos de ametista nos depósitos de classe mundial da província vulcânica do Paraná e é apresentada uma primeira descrição da estrutura, um guia prospectivo para depósitos se adiciona. / We report the discovery of a large number of gossans in the intraplate Paraná volcanic province, South America, based on observations of satellite images and field work associated with rock geochemistry and geophysics. We thus define a straitforward propecting guide for agate and amethyst deposits. The study area is located on the border between Brazil and Uruguay, covering the Quaraí mining district and the Los Catalanes gemological district. Anomalies in Google Earth satellite images were identified above six mines in the Los Catalanes gemological district, characterized in the pampas of the region as irregular structures of intense green color and sometimes with brownish, rough texture. The vegetation, scintillometric and geochemical anomalies occur at several stratigraphic levels in the volcanic group. Three scintillometric sections performed on the Maurício mine in the Los Catalanes gemological district indicate low emission rates near 55 cps (sd = 4.7) in the gossan compared with the regional average of colada Cordillera (63 cps). Whole rock geochemical analyses of three samples collected within the underground mine indicate high loss on ignition (4.5, 3.4, 4.5 wt.%). LOI higher than 2% is considered a strong indicator of intense hydrothermal alteration in the gossan. In the Quaraí mining district, gossans were studied in five areas, two in colada Catalán, two in colada Muralha, and one in colada Cordillera. The world-class deposits of amethyst and agate geodes are in coladas Catalán and Cordillera. Negative radiometric anomalies (higher than one standard deviation) occur in these gossans. The detailed study of one gossan included a geophysical grid spacing of 50 x 50 m (K, U, Th and total emission rate) and whole rock geochemical analyses (ACME, Canadá). The whole rock geochemical analyses of 20 samples collected within and outside the gossan classify the rocks as basaltic andesites, low–Ti, Gramado chemical type. The samples inside the gossan display high values of loss on ignition (2.3, 2.8, 2.9, 2.8, 2.9, 2.4, 2.6, 2.6, 2.3 and 2.3 wt.%), while outside the gossan the values are lower (0.8, 2.3, 0.5, 0.5, 1.6, 0.5, 0.6, 0.7, 1.1, 1.3 and 1.9 wt.%). SiO2, K2O and Rb show strong negative correlation with loss on ignition, while MgO has a slight enrichment. The low scintillometry in the gossan is defined primarily by the lower K2O of the altered rock. We thus report the discovery of gossans above amethyst geodes in the world-class deposits of the Paraná volcanic province and present a first description of the structure, a straitforward prospecting guide for additional deposits.

A região de Lavras do Sul (RS) possui mineralizações de metais básicos e de ouro, disseminadas e filoneanas, associadas a zonas de alteração hidrotermal. O trabalho realizado tem por objetivo a identificação, nesta região, de áreas com alteraçôes hidrotermais com o apoio de técnicas de sensoriamento remoto. Na cena 222/81 do sensor TM/Landsat-5 de 15/01/1986, ano de muito baixa pluviosidade, foram identificadas feições espectrais destacadas em uma antiga mina aurífera da região, o Bloco do Butiá, localizada 3 km à oeste da cidade de Lavras do Sul. Esta área foi selecionada como área piloto e utilizada como guia na interpretação das imagens por ter as zonas de alteração, paragêneses e estruturas já descritas na bibliografia. As imagens foram geradas a partir do conjunto das seis bandas espectrais por meio de processamento e análise digital e analógica. Uma cena ASTER deste local também foi utilizada, para identificar alteraçõoes hidrotermais. As subcenas destas imagens foram redimensionadas de forma a compreender o Complexo Intrusivo Lavras do Sul e as principais formações adjacentes ou próximas nas quais ocorrem mineralizações associadas à intrusão. O comportamento espectral dos alvos geológicos identificados realçou as anomalias espectrais nas imagens por meio de operações aritméticas entre bandas, da aplicação da técnica de análise das componentes principais e a geração de composições coloridas RGB. Nestas imagens, que permitiram a visualização das anomalias, se procedeu à seleção preliminar dos alvos a serem vistoriados em campo. Para refinamento da seleção foi utilizado um mapa de lineamentos construído a partir da aplicação de filtros direcionais nas imagens, seguido da fotointerpretação. A verificação em campo das áreas selecionadas por esta técnica confirmou algumas ocorrências de rochas hidrotermalizadas, algumas com sulfetos ou fortemente alteradas. Algumas ocorrências de feições espectrais distintivas nas imagens não foram relacionadas à alteração em campo. As assinaturas espectrorradiométricas de algumas amostras, obtidas em laboratório, quando comparadas com padrões minerais, permitiram estabelecer a correlação dessas feições espectrais com os alvos observados nas imagens. Dados de petrografia me rochas vulcânicas, piroclásticas, hipabissais e plutônicas permitiram caracterizar a alteração propilítica com a dominante destacando-se clorita, epidoto e carbonato como fases de alteração. Esses resultados sugerem que a aplicação do sensoriamento remoto na identificação de alterações hidrotermais na região de Lavras do Sul permite identificar novos alvos para prospecção. Estudos mais detalhados, com imagens de sensores hiperespectrais, podem auxiliar no mapeamento das zonas de alteração fornecendo importantes subsídios para trabalhos de prospecção mineral e o estudo da gênese das mineralizações. / Occur in the region of Lavras do Sul (RS), mineralization of gold and base metals, disseminated and filonean, associated with areas of hydrothermal alteration. The work aims at identifying, in the region, areas with hydrothermal alteration not mapped, through the use of remote sensing techniques. In a scene from the sensor TM/Landsat-5 spectral features were identified in an area where is located an old gold mine in the region, the Bloco do Butiá, located 3 km to the west of the city of Lavras do Sul, which is selected as the area pilot and used as a guide in interpreting the images to have the zones of alteration, paragenesis and structures already described in the literature. The images were generated from the set of six spectral bands from the scene of sensor TM/Landsat-5 obtained in 1986, years of low rainfall, through processing and analysis of digital and analog products. A scene ASTER was used but did not provide satisfactory results in the context of the project. The Subscene used was scaled in order to cover the Complexo Intrusivo Lavras do Sul and the main formations adjacent or near where mineralization occurs associated with the intrusion. The spectral behavior of the targets was identified through enhancements in the images, arithmetic operations between bands, the technique of principal components and the generation of RGB color compositions, which allowed their view on which are carried out preliminary selection of targets to be surveyed in field. To refine the selection we used a map of lineaments constructed from the application, on the images, of linear directional filters and by remote sensing. The scanning on field of the selected areas by this technique confirmed the occurrence, in some of the targets, of rocks with hydrothermal alteration, with some sulfides or heavily modified, and the occurrence of distinctive features in some areas not related to the alteration. The spectral signatures of the samples obtained in the laboratory were compared with standard minerals and partially succeeded in establishing its correlation to the spectral features of targets observed in the images. Data of petrography in volcanic, pyroclastic, hypabissal and plutonic rocks allowed to characterize the changes as propilitizações with the predominance of chlorite, epidote and carbonate as alteration phases. The results suggest that the application of remote sensing in identifying hydrothermal alterations in Lavras do Sul is feasible. More detailed studies with hyperspectral images can help in mapping the areas of alteration and provide important insights into mineral prospecting and study of the genesis of the mineralization.