This research is motivated by an issue frequently encountered in water quality monitoring and ecological assessment. One concern for researchers and watershed resource managers is how the biological community in a watershed is affected by human activities. The conventional single model approach based on regression and logistic regression usually fails to adequately model the relationship between biological responses and environmental stressors since the study samples are collected over a large spatial region and the response-stressor relationships are usually weak in this situation. In this dissertation, we propose two alternative modeling approaches to partition the whole region of study into disjoint subregions and model the response-stressor relationships within subregions simultaneously. In our examples, these modeling approaches found stronger relationships within subregions and should help the resource managers improve impairment assessment and decision making. The first approach is an adjusted Bayesian classification and regression tree (ABCART). It is based on the Bayesian classification and regression tree approach (BCART) and is modified to accommodate spatial partitions in ecological studies. The second approach is a Voronoi diagram based partition approach. This approach uses the Voronoi diagram technique to randomly partition the whole region into subregions with predetermined minimum sample size. The optimal partition/cluster is selected by Monte Carlo simulation. We propose several model selection criteria for optimal partitioning and modeling according to the nature of the study and extend it to multivariate analysis to find the underlying structure of response-stressor relationships. We also propose a multivariate hotspot detection approach (MHDM) to find the region where the response-stressor relationship is the strongest according to an R-square-like criterion. Several sets of ecological data are studied in this dissertation to illustrate the implementation of the above partition modeling approaches. The findings from these studies are consistent with other studies. / Ph. D.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The knowledge of the role of physical and biological processes on animal community distribution is influenced by the spatial scale adopted in ecological studies. Due the scarcity of studies of distributional patterns of benthic macroinvertebrates in multiple scales in tropical and subtropical regions, this paper analyzes the structure of benthic macroinvertebrate communities in different spatial scales (among small watersheds and different river orders of each watershed) and the influence of certain environmental variables on these communities. The sampling was performed with Surber sampler in the small watersheds of the Vacacaí-Mirim River (August, 2008), and the Ibicuí-Mirim and Tororaipí rivers (August 2009). In each watershed were selected four sampling sites following the longitudinal gradient (stretches of 1st, 2nd, 3th and 4th orders. The environmental factors analyzed were: water temperature, pH, electrical conductivity, dissolved oxygen, substrate granulometry and presence of aquatic and riparian vegetation. A total of 10.985 individuals, 42 families and 129 taxa were collected and, in general, the dominant taxa were Simuliidae (14%), Naididae (13%), Cricotopus sp. 1 (13%), Cricotopus sp. 2 (8%) (Chironomidae), Paragripopteryx (5%) (Gripopterygidae) and Americabaetis (5%) (Baetidae) representing 58% of the total specimens collected. There were no differences in macroinvertebrate richness among watersheds, however, the community structure showed differences among the three watersheds. The stretches of 3th and 4th orders showed higher richness than the stretches of 1st and 2nd orders. Additionally, there was recorded difference among communities structure of different orders stretches (56%). In general the environmental variables that influenced the distribution of the communities were granulometry, dissolved oxygen, electrical conductivity and aquatic vegetation. The macroinvertebrates characteristic of 1st and 2nd order stretches of the Vacacaí-Mirim River and of 1st order of the Tororaipí River watersheds where influenced mainly by bigger granulometry and dissolved oxygen, while the macroinvertebrates associated to the 3th and 4th order stretches were influenced by the higher electrical conductivity. The small watersheds of the Ibicuí-Mirim (except the 2nd order stretch) and Tororaipí rivers (except the 1st and 4th order stretches) did not show difference concerning the river orders, and were associated to the smaller electrical conductivity and absence of aquatic vegetation. The 4th order stretches of the Tororaipí River was segregated of the other stretches due to its smaller granulometry. The granulometry did not influence the small watershed of the Ibicuí-Mirim and Tororaipí rivers (except the 4th order stretches) due to the presence of fine substrate, while the Vacacaí-Mirim River watershed showed coarse substrate. This difference is probably determined by the fact that the Vacacaí-Mirim River represents a tributary of a different and bigger hydrographic watershed, the Jacuí River Basin, while the others small watersheds represents tributaries of the Ibicuí River Basin. Possibly, the Jacuí River Basin have higher electrical conductvity, since this factor was high in all the sampled stretches, being encreased by the proximity to urban areas with domestic sewage and agricultural activities near the river banks. In the small watersheds of the Ibicuí-Mirim and Tororaipí rivers, the difference between the community structures is possibly related to environmental features, such as finer substrate in both rivers and well developed riparian vegetation in the Tororaipí River. / As percepções dos processos físicos e biológicos dependem da escala em que as observações são feitas. Devido à escassez de estudos sobre os padrões de distribuição de macroinvertebrados bentônicos em múltiplas escalas em regiões tropicais e subtropicais, o objetivo deste estudo foi analisar a estruturação das comunidades de macroinvertebrados bentônicos em diferentes escalas espaciais (entre microbacias e entre trechos de diferentes ordens de cada riacho) e identificar a influência de variáveis ambientais sobre a estruturação dessas comunidades. A amostragem foi realizada com amostrador tipo Surber, nas microbacias dos rios Vacacaí-Mirim (agosto de 2008), Ibicuí-Mirim e Tororaipí (agosto de 2009). Em cada microbacia foram selecionados quatro pontos de coleta segundo gradiente longitudinal (trechos de 1ª, 2ª, 3ª e 4ª ordens). Em cada ponto de coleta foram amostradas as variáveis ambientais: temperatura da água, pH, condutividade elétrica, oxigênio dissolvido, granulometria do substrato e presença de vegetação aquática e ripária. Um total de 10.985 indivíduos, 42 famílias e 129 táxons foram coletados, sendo que os táxons dominantes foram Simuliidae (14%), Naididae (13%), Cricotopus sp. 1 (13%), Cricotopus sp. 2 (8%) (Chironomidae) e Paragripopteryx (5%) (Gripopterygidae) e Americabaetis (5%) (Baetidae), perfazendo 58% da abundância total. Não houve diferença na riqueza entre as microbacias, entretanto ocorreu diferença na estrutura das comunidades das três microbacias. As microbacias dos rios Tororaipí e Ibicuí-Mirim apresentaram menor diferença entre si, que em relação à microbacia do Rio Vacacaí-Mirim. Os trechos de 3ª e 4ª ordens apresentaram maior riqueza que os trechos de 1ª e 2ª ordens. Adicionalmente, ocorreu diferença na estrutura das comunidades entre os trechos amostrados (56%), sendo que apenas os trechos de 2ª e 3ª ordens não apresentaram diferença significativa entre si. De modo geral, as variáveis ambientais que influenciaram a distribuição da comunidade foram a granulometria, a concentração de oxigênio dissolvido, a condutividade elétrica e a vegetação aquática. Os macroinvertebrados típicos dos trechos de 1ª e 2ª ordens da microbacia do Rio Vacacaí-Mirim e de 1ª ordem do Rio Tororaipí foram influenciados principalmente pela maior granulometria e concentração de oxigênio dissolvido, enquanto os associados aos trechos de 3ª e 4ª ordens foram influenciados pela maior condutividade elétrica. As microbacias dos rios Ibicuí-Mirim (exceto o trecho de 2ª ordem) e Tororaipí (exceto os trechos de 1ª e 4ª ordens) não apresentaram diferença quanto às ordens, sendo associadas à menor condutividade elétrica e à ausência de vegetação aquática. A granulometria não influenciou a diferenciação das microbacias dos rios Ibicuí-Mirim e Tororaipí (exceto o trecho de 4ª ordem), pois ambos possuem substrato mais fino, enquanto a microbacia do Rio Vacacaí-Mirim apresenta substrato pedregoso. Isto provavelmente se deve ao fato do Rio Vacacaí-Mirim pertencer a uma bacia hidrográfica diferente (Bacia do Rio Jacuí) das demais microbacias (Bacia do Rio Ibicuí). Possivelmente a maior condutividade elétrica seja típica da primeira Bacia, visto que esta foi maior em todos os trechos amostrados, sendo aumentada ainda pela proximidade da área urbana, com despejo de efluentes domésticos, assim como pela presença de agricultura próxima às margens. Nas microbacias dos rios Ibicuí-Mirim e Tororaipí a diferenciação da estrutura da comunidade encontrada deve ocorrer devido às características ambientais, como presença de substrato mais fino em ambos os rios e maior quantidade de vegetação ripária no Rio Tororaipí

Introduction: Au Canada, le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes et le plus mortel après les cancers du poumon et du côlon. Il y a place à optimiser le traitement du cancer de la prostate de manière à mettre en œuvre une médecine personnalisée qui s’adapte aux caractéristiques de la maladie de chaque patient de façon individuelle. Dans ce mémoire, nous avons évalué la réponse aux dommages de l’ADN (RDA) comme biomarqueur potentiel du cancer de la prostate. Les lésions potentiellement oncogènes de l'ADN déclenche une cascade de signalisation favorisant la réparation de l'ADN et l’activation des points de contrôle du cycle cellulaire pour préserver l’intégrité du génome. La RDA est un mécanisme central de suppression tumorale chez l’homme. La RDA joue un rôle important dans l’arrêt de la prolifération des cellules dont les génomes sont compromis, et donc, prévient la progression du cancer en agissant comme une barrière. Cette réponse cellulaire détermine également comment les cellules normales et cancéreuses réagissent aux agents utilisés pour endommager l'ADN lors du traitement du cancer comme la radiothérapie ou la chimiothérapie, en plus la présence d,un certain niveau de RDA dans les cellules du cancer de la prostate peuvent également influer sur l'issue de ces traitements. L’activation des signaux de la RDA peut agir comme un frein au cancer dans plusieurs lésions pré-néoplasiques de l'homme, y compris le cancer de la prostate. Il a été démontré que la RDA est augmentée dans les cellules de néoplasie intra- épithéliale (PIN) comparativement aux cellules prostatiques normales. Toutefois, le devient de la RDA entre le PIN et l’adénocarcinome est encore mal documenté et aucune corrélation n'a été réalisée avec les données cliniques des patients. Notre hypothèse est que les niveaux d’activation de la RDA seront variables selon les différents grades et agressivité du cancer de la prostate. Ces niveaux pourront être corrélés et possiblement prédire les réponses cliniques aux traitements des patients et aider à définir une stratégie plus efficace et de nouveaux biomarqueurs pour prédire les résultats du traitement et personnaliser les traitements en conséquence. Nos objectifs sont de caractériser l'activation de la RDA dans le carcinome de la prostate et corréler ses données avec les résultats cliniques. Méthodes : Nous avons utilisé des micro-étalages de tissus (tissue microarrays- TMAs) de 300 patients ayant subi une prostatectomie radicale pour un cancer de la prostate et déterminé le niveau d’expression de protéines de RDA dans le compartiment stromal et épithélial des tissus normaux et cancéreux. Les niveaux d’expression de 53BP1, p-H2AX, p65 et p-CHK2 ont été quantifiés par immunofluorescence (IF) et par un logiciel automatisé. Ces marqueurs de RDA ont d’abord été validés sur des TMAs-cellule constitués de cellules de fibroblastes normales ou irradiées (pour induire une activation du RDA). Les données ont été quantifiées à l'aide de couches binaires couramment utilisées pour classer les pixels d'une image pour que l’analyse se fasse de manière indépendante permettant la détection de plusieurs régions morphologiques tels que le noyau, l'épithélium et le stroma. Des opérations arithmétiques ont ensuite été réalisées pour obtenir des valeurs correspondant à l'activation de la RDA qui ont ensuite été corrélées à la récidive biochimique et l'apparition de métastases osseuses. Résultats : De faibles niveaux d'expression de la protéine p65 dans le compartiment nucléaire épithélial du tissu normal de la prostate sont associés à un faible risque de récidive biochimique. Par ailleurs, nous avons aussi observé que de faibles niveaux d'expression de la protéine 53BP1 dans le compartiment nucléaire épithéliale du tissu prostatique normal et cancéreux ont été associés à une plus faible incidence de métastases osseuses. Conclusion: Ces résultats confirment que p65 a une valeur pronostique chez les patients présentant un adénocarcinome de la prostate. Ces résultats suggèrent également que le marqueur 53BP1 peut aussi avoir une valeur pronostique chez les patients avec le cancer de la prostate. La validation d'autres marqueurs de RDA pourront également être corrélés aux résultats cliniques. De plus, avec un suivi des patients plus long, il se peut que ces résultats se traduisent par une corrélation avec la survie. Les niveaux d'activité de la RDA pourront éventuellement être utilisés en clinique dans le cadre du profil du patient comme le sont actuellement l’antigène prostatique spécifique (APS) ou le Gleason afin de personnaliser le traitement. / Background: Prostate cancer is the most frequently diagnosed cancer in Canadian men and is the third deadliest after lung and colon cancers. Currently, prostate cancer treatments are based on results obtained of digital rectal exam, Gleason scores from biopsy specimens and serum PSA (Prostatic Specific Antigen) levels. The identification of specific biomarkers for diagnosis and prognosis, as well as new therapeutic targets, is quickly paving the way for personalized medicine. Ideally, in the future, patient care will include molecular signature of a patient's disease to guide for a more efficient treatment. In this thesis, we evaluated the DNA damage response (DDR) as a potential biomarker in prostate cancer. DNA lesions in mammalian cells trigger the DDR signalling cascade that orchestrates DNA repair and activate cell cycle checkpoints to preserve genome integrity. Loss of genome stability is usually associated with cancer development, and activated DDR signalling in cells with genomic instability act as a cancer barrier in several pre-neoplastic human lesions, including prostate cancer. Thus, the DDR is an important cancer suppression mechanism. The DDR is also activated in response to anti- cancer agents including radiation therapy (RT) and DNA-damaging chemotherapies. Pre- existing DDR levels in prostate cancer cells may influence the outcome of these cancer treatments. DDR signalling has been detected during human prostate cancer progression from low levels in normal prostate cells to high levels in high-grade prostatic intraepithelial neoplasia (HG-PIN). However, DDR signalling variations detected from HG-PIN to adenocarcinoma remain unclear, and no correlations were performed with patient clinical outcome data. Our hypothesis is that the levels of persistent DDR signalling activity will be variable with different grades and aggressiveness of prostate cancer. The levels of this activity could be correlated with the clinical responses to treatments and could even predict this process. We believe that having new biomarkers will help personalizing cancer treatment and certainly increase treatments’ efficiency. Our objectives are to characterize the occurrence of DDR activation in prostate carcinoma and to correlate it with patients’ survival and responsiveness to treatment. Methods: We used tissue microarrays (TMAs) from human radical prostatectomy specimens of 300 men with prostate cancer and estimated the level of DDR protein expression in the stromal and epithelial compartments of normal and aggressive cancer tissues. The expression level of the DDR markers p53 binding protein-1 (53BP1), phosphorylated H2AX (p-H2AX), p65 (p65 subunit of Nuclear Factor (NF-κB) and phosphorylated checkpoint kinase-2 (p-CHK2) was quantified using immunofluorescence (IF) coupled to high-content automated imaging. The quantification of our DDR markers was first validated on an experimental TMA (TMA-cell) including normal and irradiated (to induce DDR signalling) cultured human fibroblasts. The data was quantified using binary layers commonly used to classify pixels in an image so areas could be analysed independently allowing the segregation of specific compartments including nuclei, epithelia and stroma. Arithmetic operations were performed to render values corresponding to DDR activation that were then correlated with clinical outcomes such as biochemical recurrence and occurrence of bone metastasis. Results: We found that low levels of p65 protein expression in the nuclear epithelial compartments of normal prostate tissue were associated with a reduced probability of biochemical failure (which corresponds to a rise in the serum level of PSA in prostate cancer patients following treatment, surgery in this cohort of patients). Moreover, we also observed that low levels of 53BP1 protein expression in the nuclear epithelial compartments of normal and cancerous prostate tissue were associated with a lower incidence of bone metastasis. Conclusion: These results confirm that p65 has prognostic value in patients with prostate adenocarcinoma. Based on our results, we suggest that 53BP1 marker may have a prognostic value as well. The validation of other markers and particularly DDR markers may correlate with patients’ outcome. With longer follow-up, it may translate into correlation with survival. Levels of DDR activity in cancer tissue could be used in daily clinic as part of the patient’s diagnostic profile as much as his prostatic specific antigen (PSA) or Gleason score in order to predict response and personalize the treatment in order to guide the patients towards the most appropriate treatment amongst all those available for their prostate cancer.

The aim of this work is to evaluate the current procedures and to indicate the development of the cataloging practice towards the RDA rules based on research and analysis of bibliographic production serials in selected Czech and foreign libraries. The diploma thesis is divided into several chapters. After introducing the issue of serial documents follows the chapter devoted to the standards and resources for cataloging the continuing resources that the catalogers should know. The next chapter deals with the FRBR and its application to the serials. Part of the chapter dealing with RDA rules from the serials perspective is also the analysis of these rules according to the FRBR structure available in the RDA Toolkit. Three chapters are devoted to the analysis of bibliographic processing, first in foreign libraries, then in Czech libraries, and in the last chapter there is a comparison of selected periodicals in foreign and Czech libraries. At the end of the thesis are presented the impacts of application of the FRBR model and RDA rules on serials cataloging. Keywords serials - periodicals - continuing resources - rules RDA - FRBR - FRBRoo - PRESSoo - cataloging - bibliographic record - library

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Ce travail se propose d´étudier le rapport entre la filiation et l´écriture de l´Histoire chez deux écrivains contemporains : le Français Patrick Modiano et la romancière allemande Monika Maron. Chez ces auteurs, le « roman familial » constitue un accès privilégié à l´Histoire. Après avoir replacé les deux écrivains dans leurs paysages littéraires respectifs et précisé des notions utiles comme l´autobiographie, l´autofiction et le roman familial, le travail s´attache à dégager les figures de la filiation dans les deux œuvres en confrontant les données biographiques à leurs transpositions romanesques. Une étude des structures narratives montre ensuite que le passé et l´Histoire n´interviennent pas seulement au niveau thématique mais influencent jusqu´à la forme du récit. Un intérêt tout particulier est porté aux modalités d´une écriture de l´Histoire qui se révèle complexe, entre objectivité historique, fantasme et fiction. L´approche par la filiation confère à l´écriture de l´Histoire une forte dimension mémorielle. La question de l´identité se pose alors en termes d´héritage familial et historique. En cela, Patrick Modiano et Monika Maron s´inscrivent dans l´ensemble plus large d´une littérature « générationnelle » de la seconde moitié du XXe siècle. / This study deals with the relationship between filiation and the writing of history in the works of two contemporary authors, the French author Patrick Modiano and the German novelist Monika Maron. Both authors approach history mainly through family romance. First, the two authors are situated in their respective literary environment, and some key notions are developed in detail, such as autobiography, autofiction, and family romance. On that basis, the fictional characters that bear marks of filiation are portrayed by confronting biographical facts with their fictional transpositions. A subsequent analysis of narrative structures reveals that the past and history do not only have an impact on contents, but also on the form of the narrative. Special attention is paid to the way history is told, which turns out to be complex, oscillating between historical objectivity, fantasy, and fiction. The access to history through family romance empha! sizes the memorial aspect of the writing of history. Consequently, personal identity is defined in terms of heritage, both family heritage and historical heritage. In this respect, Patrick Modiano and Monika Maron belong to an entire school of writing, the “generational literature” of the second half of the 20th century.

Pour les Juifs rescapés de la Shoah, établir une vie nouvelle sur le territoire allemand après 1945 était quasiment impensable. En particulier à Berlin, l’ancienne capitale du IIIe Reich, devenue le point de cristallisation des relations Est-Ouest, l’entreprise paraissait improbable, à tel point que la conception de la communauté de « liquidation » a dominé jusque dans les années 1950. Et pourtant, la [re]construction s’est opérée malgré tout, sous les auspices de la division allemande, qui n’a pas épargné la Communauté Juive de Berlin. L’analyse comparative des Juifs à Berlin-Est et à Berlin-Ouest, sur les plans démographique, religieux, politique et culturel, révèle certes de fortes disparités, liées plus ou moins directement aux caractéristiques des régimes de la RFA et de la RDA ; mais au-delà de ces clivages indéniables, il est possible de mettre en lumière un certain nombre de valeurs et de préoccupations communes aux Juifs dans les deux Berlin, ainsi que des phénomènes de passage jusqu’alors peu étudiés. / For the Jews who had survived the Shoah, to establish of a new life on the German territory after 1945 was almost unthinkable. Particularly in Berlin, the former capital of the third Reich, which became the nodal point of the East-West relations, the attempt seemed most unlikely. As a result, the conception of a community of “liquidation” dominated until the 1950’s. Yet, [re]construction took place, in spite of everything, in the context of the partition of Germany, which didn’t spare the Jewish Community of Berlin. The comparative analysis of the Jews in East- and West-Berlin at the demographic, religious, political and cultural levels does reveal strong disparities, which are more or less linked with the features of the East-German and West-German systems; but beyond these undeniable divides, it is possible to bring to light common values and concerns, as well as forms of crossing which have attracted little scholarly attention so far.

Since submerged macrophytes are a key primary producer of shallow lakes and are sensitive to environmental changes, macrofossils of them can be used in investigations of past environmental conditions, to infer human introduced environmental impacts (e.g. eutrophication) and to determine past macrophyte communities. The present study includes twenty six shallow lakes, which were chosen along a latitudinal gradient ranging from the North (41&deg / 52&acute / N, 27&deg / 58&acute / E) to the South (37&deg / 06&acute / N, 29&deg / 36&acute / E) in Turkey. Sampling for environmental variables and sediment was carried out using a snap-shot sampling protocol (developed within the framework of the EU FP6 project &lsquo / Eurolimpacs&rsquo / ) during the summers of three consecutive years (2006-2008). Surface sediment, short core and long core samples were retrieved from the lakes. The aims of this study were i. to compare the surface sediment plant macrofossils with present day macrophyte taxa of the lakes, ii. to determine the environmental variables potentially influencing the temporal changes in macrophyte communities, and iii. to assess vegetation community dynamics in dated short and long cores. Comparison of plant macrofossil assemblages in surface sediment with present day macrophyte coverage revealed that approximately 41% of the modern taxa were represented among the surface sediment macrofossils. Redundancy analysis (RDA) was carried out for surface macrofossil data with corresponding environmental data. RDA revealed relation of plant species and environmental variables (e.g. Salinity and Najas marina L.). Changes in plant species assemblages in short and long cores from eight lakes chosen along a latitudinal gradient ranging from North to South Turkey is discussed in relation to the RDA results.

Dissertation--Bonn--Universität, 2002. / SED = Sozialistische Einheitspartei Deutschlands, PDS = Partei des demokratischen Sozialismus. Bibliogr. p. 293-321.

Diss.--Berlin, 1998. / Includes bibliographical references (p. [339]-353) and index.