Made available in DSpace on 2015-05-08T14:53:37Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3740949 bytes, checksum: 4b4bb1e725e28d0a9a489835e70b4e60 (MD5) Previous issue date: 2014-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Find emergency public services falls into one of the classic optimization problems where points are available for candidates who are chosen, among them, those that optimize the efficiency criteria established, to find a limited number of facilities. The set of candidate sites have great influence on the final solution generated by a model location . In the research, three strategies were used to elect local candidates to position the cars of police : decision of the Security Manager , p-median model and method of clustering k-means. With the support of Geographical Information Systems (GIS ) it was possible to georeference the occurrences of crimes , to visualize the distribution of selected local candidates and identify the presence of hotspots of crime. Aiming to solve the problem of allocating vehicles adopted two approaches : exact and heuristic . Therefore, two hybrid meta - heuristics were implemented - GRASP combined with VND and GRASP with exact model. They obtained same or very approximate solutions of the optimal solution . It was developed a system of spatial decision support based on the solution of the formulation of the problem of locating facilities with restricted coverage and backup coverage. It is a Web tool built with by WebGIS technology / Localizar serviços públicos emergenciais se enquadra em um dos problemas clássicos de otimização onde pontos candidatos são disponibilizados para que sejam escolhidos, dentre eles, aqueles que otimizem o critério de eficiência estabelecido, visando localizar um número limitado de facilidades. O conjunto de locais candidatos tem grande influência sobre a solução final gerada por um modelo de localização. Na pesquisa, foram definidas três estratégias para eleger os locais candidatos ao posicionamento de viaturas policiais: decisão do gestor de segurança, modelo de Pmedianas e método de clusterização k-means. Com apoio de Sistemas de Informação Geográfica (SIG) foi possível georreferenciar as ocorrências de crimes, visualizar a distribuição dos locais candidatos selecionados e identificar a presença de hotspots de crimes. Visando resolver o problema de alocação de viaturas adotou-se duas abordagens: exata e heurística. Para tanto, duas meta-heurísticas híbridas foram implementadas - GRASP combinado com VND e GRASP com modelo exato, as quais obtiveram soluções iguais ou muito aproximadas da solução ótima. Foi desenvolvido um sistema de apoio a decisão espacial baseado na solução da formulação do problema de localização de facilidades com restrições de cobertura e cobertura backup. Trata-se de uma ferramenta WEB construída com base os padrões usados pela tecnologia WebGIS

Biomes classified as Brazilian Atlantic Forest (BAF) and the Chilean Mediterranean forest (CMF) have been affected by anthropic pressure that has caused a considerable decrease of their forest surfasse. However, they are rich in biodiversity and they provide many ecosystem services and were, therefore, classified as \"hotspots\" (forests in risk). Therefore, is essential to study the natural dynamics and the climatic response of the trees of these forests to include conservation projects and strategic measures. To achieve these objectives, the scientific literature reports that tree growth rings are the only ecological indicators with annual resolution that can be efficient and highly accurate to obtain this information. In this context, the research project has as main objective the retrospective analysis of radial growth of forest species in different vegetation communities of BAF and CMF in response to climatic changes. To achieve this goal, four key questions were elaborated: 1) Which variable explains betterthe variability of radial growth at different spatial and temporal scales? 2) What is the growth resilience to recent climate changes? 3) Is there some more vulnerable population to expected climatic changes?. A total of five sites (seven populations) of Cedrela odorata and C. fissilis in BAF from the State of São Paulo in Brazil, and five sites (10 populations) of Nothofagus macrocarpa (FMC) from the central region of Chile were sampled, using a non-destructive method. Four chapters were developed to answer these questions. Chapter I seek to analyze the resilience in radial growth to changes in regional climate variability and droughts, in temporal and spatial scale, on Atlantic forest remnant forests of biogeographic region Serra do Mar. Results show that radial growth in wet sites (winter rains exceed 240 mm) depend on the moisture conditions in dry season, while the higher population is more sensitive to the favorable summer water condition, which would be explained because this population received a lower temperature than the other Cedrela spp. populations studied. Chapter II analyzed how recent climatic variability affected the radial growth in N. macrocarpa populations. It is observed that all the populations are closely linked to the precipitations of May-November (end of autumn/end of spring) and average temperature of October-December (mid-spring/early summer). In Chapter III, we continued exploring the growth responses to climate in the FMC populations in order to find biogeographic differences. In this sense, we evaluated if this significant decrease in tree growth is differentiated between populations and age classes, and determine if the positive effect of CO2 fertilization compensates the precipitation decrease and temperature increase in the last decades in the growth of older, maturer and younger trees . Results show a significant negative trend in all classes from the year 2000, which would be associated to a decrease in precipitation in all populations while temperature was more associated with the northern and southern populations (distribution limit). We did not find a positive effect of rising CO2. Finally, chapter IV integrated the results of the two biomes comparing the projections of aboveground trees biomass under two climatic scenarios of CMIP5 project (light and severe), in order to know which populations are more vulnerable to rising temperature forecasted by year 2100, using ring width data, wood density and allometric equations. This study will provide an overview of adaptation to recent and projected climatic changes of two hotspot neotropical biomes. Although they are different in structure-biodiversity-climate are in risk. Thus, we can understand the vulnerability of threatened forests in South America to global warming that, although they are in protected areas, does not guarantee their persistence. / Os biomas classificados como Mata Atlancia Brasileira (MAB) e da Floresta Mediterrânea Chilena (FMC) têm sido afetados pela pressão antrópica que tem causado uma diminuição considerável de sua superfície florestal. No entanto são ricas em biodiversidade e providenciam muitos serviços ecossistêmicos, pelo que foram classificadas como hotspot (florestas em risco). Portanto, é fundamental estudar a dinâmica natural e a resposta climática das árvores dessas florestas para incluir em projetos de conservação. Para atingir esses objetivos, a literatura científica reporta que os anéis de crescimento das árvores são os únicos indicadores ecológicos com resolução anual que podem ser eficientes e de elevada precisão para obter essas informações. Neste contexto, o projeto de pesquisa tem como objetivo geral a analise retrospectivo de crescimento radial de espécies florestais em diferentes comunidades vegetacionais da MAB e FMC em resposta às mudanças climaticas. Para atingir esse objetivo foram elaboradas quatro perguntas-chave: 1) Que variable explica melhor a variabilidade do crescimento radial a diferentes escalas espaciais e temporais? 2) Qual é a resiliência em crescimento das árvores às mudanças climáticas recentes? 3) Há alguma população mais vulnerável respeito às mudanças climaticas esperadas?. Foram coletadas amostras de lenho, através de método não destrutivo, de cinco sitios (sete populações) de Cedrela odorata e C. fissilis na MAB no estado de São Paulo em Brasil, e cinco sitios (10 populações) de Nothofagus macrocarpa na FMC na região central do Chile, para aplicação de tecnicas dendrocronologicas. Para responder essas questões foram desenvolvidos quatro capitulos. O capitulo I busca analisar a resiliência em crescimento radial às mudanças na variabilidade climática regional e secas, em escala temporal e espacial, em florestas remanentes da região biogeográfica Serra do Mar da Mata Atlântica, usando as especies bioindicadoras Cedrela fissilis and C. odorata. Os resultados mostram que o crescimento radial dos sítios mais úmidos (chuvas no inverno superam os 240 mm) dependem das condições hidricas da estação seca, enquanto que a população mais alta é mais sensível à condição hídrica favorável do verão, qual seria explicado porque essa população recebi uma menor temperatura respeito às outras populações de cedrela estudadas. No capitulo II analisou-se como a variabilidade climática recente estaria afeitando o crescimento radial in N. macrocarpa populations. Observa-se que todas as populações estão estreitamente ligadas às precipitações de Maio-Novembro (fim de outono/fim de primaveira) e temperatura média de Outubro-Dezembro (mediados de primaveira/inicios do verão). Especificamente, há uma tendencia negativa significativa no crescimento radial apartir de 1980 que esta associada a uma variação do clima regional. No capitulo III, continuo-se explorando as respostas do crescimento radial ao clima nas populações da FMC com objetivo de encontrar diferencias biogeográficas. Neste sentido, foi avaliado se essa diminuição significativa de crescimento é diferenciada entre populações e classes de idade, e analisar se o efeito positivo da fertilização de CO2 compensa a diminuição da precipitação e aumento da temperatura nas ultimas decadas no crescimento de árvores velhos, maduros e jovens. Os resultados mostram uma tendencia negativa significativa em todas as clases apartir do ano 2000, qual estaria associada a diminuição da precipitação em todas as populações enquanto a temperatura teve mais associada às populações do sul. Não foi encontrado um efeito positivo do aumento de CO2. Finalmente, o capitulo IV integrou os resultados dos dois biomas comparando as proyeções de biomasa arborea sob dois escenarios climáticos do projeto CMIP5 (leve e severo), com objetivo de conocer quais populações são mais vulneraveis ao aumento da temperature previsto para o ano 2100, usando crescimento radial, densidade de madeira e ecuações alométricas. Os resultados mostram que a população com maior influencia urbana e a mais seca são as mais vulneráveis ao aumento exarcerbado de temperatura nas regiões de MAB and FMC, respectivamente. O presente estudo permitiu-nos apresentar uma visão da adaptação às mudanças climáticas recentes e projetadas de dois biomas hotspot. Embora sejam diferentes em estrutura-biodiversidade-clima estão em risco. Assim, podemos entender a vulnerabilidade de florestas neotropicais ao aquecimento global, embora estejam em áreas protegidas, não garante sua persistência.

Embora recifes de coral sejam hotspots de biodiversidade para corais e peixes, não se sabe se são para pequenos invertebrados marinhos. Este estudo visou verificar se o complexo recifal Sebastião Gomes é um hotspot de biodiversidade de poliquetas, bem como caracterizar a comunidade estrutural e funcional desses organismos que habitam o sedimento ao redor do recife. Através de modelos lineares generalizados (glm), tendo como variáveis preditoras características do sedimento e/ou posicionamento das estações de coleta ao redor do recife (transectos perpendiculares às faces sul, oeste, norte e leste), buscou-se compreender os padrões de: diversidade alfa; abundância total de poliquetas; abundância das espécies mais representativas; e abundância dos diferentes hábitos tróficos. Foram coletados 2399 indivíduos identificados em 116 espécies, indicando que Sebastião Gomes pode ser um hotspot. Todos descritores da comunidade foram maiores próximos ao recife, onde predominaram sedimentos grossos e carbonáticos. Já a posição ao redor do recife foi importante apenas para alguns descritores, tais como abundância total e dos hábitos tróficos carnívoros e detritívoros, todos maiores nos transectos norte e leste, expostos aos ventos. A abundância de poliquetas foi mais baixa em todo transecto sul, mais suscetível à ressuspensão de sedimento causada pelas frentes frias que atingem essa região / Although coral reefs are biodiversity hotspots for corals and fishes, it is not known whether they are also for small marine invertebrates. The present study aimed to verify if Sebastião Gomes reef complex is a polychaete biodiversity hotspot, as well to describe the structural and functional community of these organisms which inhabit sediments around the reef. Generalized linear models (glm) with sediment features and station position around the reef (perpendicular transects to the South, West, East and North faces) as predictor variables were used to understand the patterns of: alpha diversity; total polychaete abundance; most representative species abundance; and abundance of different trophic habits. 2399 individuals identified in 116 species were collected, indicating that Sebastião Gomes may be a hotspot. All community descriptors were higher near the reef, where coarse and carbonate sediments preponderate. However, the position around the reef was important only for some descriptors, such as total abundance and abundance of carnivorous and deposit feeders. All of them higher in the North and East transects, that are exposed to wind. The polychaete abundance was lower in the whole South transect, nevertheless it is more susceptible to sediment resuspension caused by cold fronts that reach the region

Contrairement aux maladies génétiques mendéliennes, qui dépendent d’un seul gène causal, les traits quantitatifs complexes sont des caractéristiques mesurables d’organismes vivants, qui résultent de l’interaction entre plusieurs gènes et les facteurs environnementaux. La génomique fonctionnelle nous a permis d’identifier de nombreux locus génétiques liés aux caractères complexes, qui sont appelés «locus de traits quantitatifs» (QTL). Cependant, de telles études ne permettent pas une caractérisation précise de l'architecture génétique des traits complexes. Plus récemment, il est devenu possible d’identifier des locus génétiques associés aux niveaux d'expression de gènes, appelés«locus de traits quantitatifs d’expression» (eQTLs). Dans de tels cas, les variants génétiques peuvent affecter l'expression soit des gènes qui se situent dans leur voisinage (cis-eQTLs), soit de ceux qui résident plus loin (trans-eQTLs). Dans des cas particuliers, un même locus peut affecter l’expression de plusieurs gènes situés dans différents chromosomes, formant ce qu’on appelle des ‘trans-eQTLs hotspots’. Ceux-ci peuvent avoir d’importants intérêts biologiques, car ils sont généralement enrichis en gènes fonctionnellement apparentés qui peuvent influencer le même trait phénotypique. Dans cette thèse, en analysant l'expression des gènes dans des échantillons de cœurs obtenus à partir d'un panel de souches consanguines recombinantes de souris AxB / BxA, nous avons détecté un QTL lié en trans- à l'expression de 190 transcrits, dont la majorité est connue pour être sensible aux interférons de type I. Le même locus correspondait également à celui d'un cis-eQTL pour le gène Ypel5, ce qui suggère que ce dernier peut être un régulateur commun des gènes trans-eQTL. Donc, le but principale de cette thèse fut de valider biologiquement le rôle du gène cis-eQTL dans la régulation du ‘trans-eQTLs hotspots’. Les travaux présentés dans cette thèse ont montrés que la réduction de l'expression de Ypel5 dans des macrophages de souris a stimulée l'expression de plusieurs gènes qui appartiennent au ‘trans-eQTL hotspot’, et ce d’une manière dépendante d’IFNB1. Le knockdown de YPEL5 a également augmenté l’induction d’IFNB1 dans les cellules humaines HEK293T. Lorsque ces dernières ont été soumis à des stimuli qui activent les kinases TBK1 / IKBKE, nous avons détecté des interactions fonctionnelles de YPEL5 avec l'activité de ces kinases, ainsi que des interactions physiques avec IKBKE. Nos résultats préliminaires (présentés dans le chapitre3) suggèrent aussi l’implication de YPEL5 dans la régulation du cycle cellulaire et /ou de la sénescence. En conclusion, nous sommes parmi les premiers groupes à fournir des preuves biologiques montrant le rôle d'un gène cis-eQTL en tant que régulateur commun de gènes appartenant à un ‘hotspot de trans-eQTL’. La validation biologique des analyses génomiques a ainsi permis de découvrir Ypel5 comme un nouveau régulateur négatif de la réponse antivirale innée qui agit (au moins en partie) au niveau des kinases TBK1 / IKBKE. / Unlike Mendelian genetic diseases, which depend on a single causal gene, complex quantitative traits are measurable characteristics of living organisms, which result from the interaction between several genes and environmental factors. Functional genomics has allowed us to identify many genetic loci linked to complex traits, which are called "quantitative trait loci" (QTL). However, such studies do not allow an accurate characterization of the genetic architecture of complex traits. More recently, it has become possible to identify genetic loci associated with gene expression levels, called "expression quantitative trait locus" (eQTLs). In such cases, the genetic variants can affect the expression of genes that are either located in their vicinity (cis-eQTLs) or that reside further away (trans-eQTLs). In particular cases, the same locus can affect the expression of several genes located on different chromosomes, forming so-called ‘trans-eQTLs hotspots’. These may have important biological interests, as they are generally enriched in functionally related genes, which may influence the same phenotypic trait. In this thesis, by analyzing the expression of genes in hearts from a panel of AxB / BxA mouse recombinant inbred strains, we detected a QTL linked in trans- to the expression of 190 transcripts, the majority of which are known to be sensitive to type I interferon. The same locus also corresponded to that of a cis-eQTL for the Ypel5 gene, suggesting that it could be a common regulator of the trans-eQTL genes. Therefore, the main purpose of this thesis was to biologically validate the role of the cis-eQTL gene in the regulation of the ‘trans-eQTL hotspot’. The work presented in this thesis showed that the silencing of Ypel5 expression in mouse macrophages stimulated the expression of several genes that belong to the ‘trans-eQTL hotspot’ in an IFNB1-dependent manner. YPEL5 knockdown also increased IFNB1 induction in human HEK293T cells. When the latter were subjected to stimuli that activate the TBK1/IKBKE kinases, we detected functional interactions of YPEL5 with the activity of these kinases and physical interactions with IKBKE. Our preliminary results (presented in Chapter 3) suggest also the involvement of YPEL5 in the regulation of cell cycle progression and / or senescence. In conclusion, we are among the first groups to provide biological evidence showing the role of a cis-eQTL gene as a common regulator of genes belonging to a ‘trans-eQTL hotspot’. The biological validation of genomic analysis thus revealed Ypel5 as a new negative regulator of the innate antiviral response that acts (at least in part) at the level of the TBK1 / IKBKE kinases.

Neste trabalho realizou-se o estudo de distribuição, riqueza e conservação do gênero Davilla Vand. (Dilleniaceae) no Neotrópico. Para tal utilizou-se a modelagem de distribuição de espécies com o algoritmo Maxent. Este produz distribuição das espécies no espaço geográfico a partir de dados ambiental e de ocorrência. Foram estudadas as espécies de acordo com o bioma de ocorrência: Mata Atlântica; Cerrado; e Amazônia. Este grupo está representado no Neotrópico por 25 espécies. Para o Cerrado incluiu-se além das espécies do gênero Davilla as demais espécies da família Dilleniaceae. Os resultados indicaram que no Cerrado o grupo está representado por nove espécies de Davilla, além de Curatella americana L. e três espécies de Doliocarpus Rol., destas cinco são endêmicas (Doliocarpus elegans Eichler e 4 Davilla spp.). Para a Mata Atlântica ocorrem 12 espécies de Davilla, oito delas são endêmicas, incluindo uma espécie ameaçada de extinção. Para a Floresta Amazônica são conhecidas nove espécies, cinco delas endêmicas. Duas outras espécies são Neotropicais, portanto, compartilhadas por todos os biomas citados anteriormente. As demais espécies são de ocorrência em pelo menos dois biomas. Para estes três biomas produziu-se a distribuição e a riqueza de espécies visando comparar os resultados com as unidades de conservação, objetivando discutir questões relativas à conservação deste grupo. Os parâmetros conservacionistas como espécies raras, zonas de endemismo, zonas de alta riqueza, áreas de preservação ambiental, foram confrontados objetivando indicar áreas prioritárias para a conservação do grupo e da biodiversidade. Os resultados indicaram existir três centros de diversidade para este grupo. O principal deles está localizado na Mata Atlântica, principalmente nas florestas litorâneas do estado da Bahia. Outro centro de diversidade localiza-se na região central do Cerrado, especialmente nos estados de Goiás e Bahia. A outra área de diversidade localiza-se próximo à foz do Rio Amazonas e ao longo de seu curso. Devido ao hábito predominante das espécies serem lianas, estas são importantes componentes das florestas, das quais usamos este referencial para discutir questões relativas à conservação destes habitats, de suas espécies e da biodiversidade. As informações completas estão apresentadas nos capítulos de acordo com os respectivos biomas abordados. / In this study was realized to study the distribution, richness and conservation of the Davilla Vand. (Dilleniaceae) in the neotropics. For this purpose was used to distribution model of species with Maxent algorithm. This produces species distribution in geographic in space based on environmental and occurrence data. Species in accordance with biome of occurrence were studied: Atlantic Forest; Cerrado; and the Amazon. This group is represented by 25 species in the neotropics. For the Cerrado was included in addition to the Davilla species all species of Dilleniaceae family. The results indicated that in the Cerrado this group is represented by nine species of Davilla, and Curatella americana L. and three species of Doliocarpus Rol., to these five are endemic (Doliocarpus elegans Eichler and 4 Davilla spp.). For Atlantic Forest occur 12 Davilla species, eight of which are endemic, including an endangered species. For the Amazon are known nine species, five of these endemic. Two other neotropical species are therefore shared by all biomes mentioned above. The other species are occurring in at least two biomes. For these three biomes produced the distribution and species richness in order to compare the results with the protected areas, aiming to discuss issues relating to the conservation of this group. Conservationists parameters as rare species, areas of endemism, areas of high species richness, conservation areas, were confronted aiming indicate priority areas for conservation of biodiversity and too this group. The results indicated three centers of diversity for this group. The main one is located in the Atlantic Forest in coastal forests of Bahia. Another center of diversity is located in central region of Cerrado, especially in the states of Goias and Bahia. The other area of diversity is located near the mouth of the Amazon River and along its course. Due to the prevailing habit of the species are lianas, these are important components of forests, of which we use this framework to discuss issues relating to the conservation of these habitats, their species and biodiversity. Full details are presented in chapters according to their biomes addressed.

Mutation des p53 Gen ist die häufigste genetische Veränderung in allen humanen Tumoren. Weit verbreitete p53 misssense-Mutationen heben die Tumor suppressive Funktion auf und führen zu gain-of-function Eigenschaften, die Tumorproliferation, Chemoresistenz, Angiogenese, Migration, Invasion und Metastasen fördern. In dieser Arbeit haben ich für drei solche Hotspot-Mutationen, p53R245Q, p53R246S und p53R270H, eine höhere Sensitivität gegenüber Behandlung mit Piperlongumine in p53-defizienten MEFs und Eµ-myc Lymphomzellen im Vergleich zur Kontrolle und den anderen drei Hotspot-Mutationen, p53R172H, p53G242S und p53R279Q, gefunden. Nachfolgend, haben ich entdeckt, dass Piperlongumine-induzierter Zelltod durch ROS Akkumulation über die Aktivierung von p38 und JNK, vermittelt wurde. Das Antioxidans N-acetyl-L-cysteine (NAC) oder p38/JNK Inhibitoren konnten vollständig oder teilweise Piperlongumine-induzierten Zelltod unterdrücken. Nach Behandlung mit Piperlongumine, haben die p53R245Q, p53R246S und p53R270H-Mutanten die Aktivierung von p21 inhibiert und so die Aktivierung und Funktion von NRF2, durch Piperlongumine induziert, blockiert, dass zu dem massiven Zelltod in Zellen mit diesen Mutationen beiträgt. Auf ähnliche Weise, verursachte der klinisch verwendete Inhibitor von Crm1, KPT-330, schweren Zelltod in p53-/- MEFs mit den p53R245Q, p53R246S und p53R270H-Mutationen. Folglich könnte Crm1 als potenzielles Target für Lymphome mit p53R245Q, p53R246S und p53R270H-Mutationen berücksichtigt werden. Zusammenfassend bekräftigen die Daten in dieser Arbeit das Phänomen, dass oxidativer Stress oder Crm1 Inhibitoren effektiv Zellen mit p53R245Q, p53R246S und p53R270H-Mutationen eliminieren können, mit niedriger Toxizität für Kontrollzellen. Demzufolge, könnten oxidativer Stress Signalwege oder Crm1 als potenzielle Angriffsziele für Lymphome mit p53R245Q, p53R246S und p53R270H-Mutationen dienen. / Mutation of the p53 gene is the most common genetic alteration among all human cancers. Prevalent p53 missense mutations abrogate its tumor suppressive function and lead to gain-of-function properties that promote cancer cell proliferation, chemoresistance, angiogenesis, migration, invasion, and metastasis. This doctoral thesis aims to identify the metabolic vulnerabilities of six p53 hotspot mutants in lymphomas. In this work, three hotspot mutants, p53R245Q, p53R246S and p53R270H, were more sensitive to piperlongumine treatment in p53-deficient MEFs and Eμ-myc lymphoma cells than the empty control and the other three hotspot mutants, p53R172H, p53G242S and p53R279Q. Thereafter, I found piperlongumine-induced cell death was mediated by ROS accumulation via the activation of p38 and JNK. Antioxidant N-acetyl-L-cysteine (NAC) or p38/JNK inhibitors could completely or partially suppress piperlongumine-induced cell death. Upon piperlongumine treatment, p53R245Q, p53R246S and p53R270H-mutant inhibited piperlongumine-induced activation of p21 and consequently attenuated the activation and function of NRF2 induced by piperlongumine, contributing to the massive cell death in cells harboring these mutants. Similarly, KPT-330, a clinical inhibitor of Crm1, also caused severe cell death in p53-/- MEFs harboring p53R245Q, p53R246S and p53R270H-mutant. This implied that Crm1 could be also considered as a potential target for lymphomas harboring p53R245Q, p53R246S and p53R270H-mutant. Taken together, data presented in this work underscore the phenomenon that exogenous oxidative stress or Crm1 inhibitor is effective in eliminating cells harboring p53R245Q, p53R246S and p53R270H-mutant with low toxicity to cells harboring the empty control, suggesting oxidative stress pathways or Crm1 as potential targets in lymphomas with p53R245Q, p53R246S and p53R270H-mutant.

Master of Science / Department of Geology / Kirsten Nicolaysen / The Kerguelen Archipelago and the submarine Northern Kerguelen Plateau consist primarily of basalt erupted by the intraplate Kerguelen hotspot. The exposed volcanic rocks are tholeiitic basalts (29 Ma) followed by lesser alkalic basalts, highly alkaline phonolites, and syenites (24 Ma). This study presents the mineralogy, isotopic and geochemical compositions of lavas (n=59) from a 650 m section exposed in the wall of a glacial valley at Trois Menestrels in the Kerguelen Archipelago. This basalt section, exposed south of the Cook Ice Cap and closest to the Raillier du Baty alkalic plutonic complex, is further south and west of previously studied basalts exposed on the Plateau Central. Results of 40Ar/39Ar dating show the Trois Menestrels lavas erupted approximately 25 Ma, approximately contemporaneously with other Plateau Central lavas and thus provide an opportunity to examine spatial compositional variations within the Kerguelen hotspot. Though the Trois Menestrels lavas are tholeiitic, The samples plot on the tholeiitic field at the stratigraphic section of Trois Menestrels, 80% of lavas from Mt. Tourmente are transitional to alkalic in the younger rocks (25.6 Ma). This sequence of tholeiitic to transitional to alkalic compositions is mirrored at Mt. Capitole and Mt. Marion Dufresne. Sr, Ba, Pb, Nb, Zr versus Nb plots show similar patterns across the Plateau Central and abundances overlap within error. Variations in isotopic composition reveal that Trois Menestrels is rather homogeneous compared to the other sections. A fundamental issue that derives from these results is the close relationship between these different rocks of the various region of the Plateau Central.

Human impacts on ocean ecosystems are driving declines in marine biodiversity, including marine mammals. Comprehensive spatial data are vital for making informed management decisions that may aid species recovery and facilitate the sustainable use of ocean ecosystems. However, marine mammal studies are often data limited, thereby restricting possible research questions. Developing novel analytical approaches and incorporating unconventional datasets can expand the scope of analysis by increasing the information content of existing data sources. The goal of our research is to support conservation and management of marine mammals in British Columbia (BC), Canada, through the application of advanced spatial statistical methodology to characterize spatial distribution and density patterns and provide assessments of data uncertainty. Our first objective is to generate statistical models to map spatially continuous predictions of marine mammal distributions and densities within BC’s north coast and apply methodology from spatial statistics to identify hotspots of elevated use. We use species observations collected from systematic line transect surveys previously adjusted to generate estimates of density per nautical mile of transect. We predict the distribution and density patterns of nine marine mammal species by employing a species-habitat model to relate species densities to environmental covariates using a generalized additive model. We use spatial statistical hotspot analysis (Getis-Ord Gi*statistic) and an aspatial threshold approach to identify hotspots of high density. Our analysis reveals that hotspots selected using a top percentage threshold produced smaller and more conservative hotspots than those generated using the Gi*statistic. The Gi*statistic demonstrates a robust and objective technique for quantifying spatial hotspots and offers an alternative method to the commonly applied aspatial threshold measure. We find that maps show agreement with prior research and hotspots align with ecologically important areas previously identified by expert opinion. Our second objective is to apply map comparison techniques to compare cetacean density maps from disparate data collection methods (systematic surveys and citizen science) to evaluate the information content of each map product and quantify similarities and differences. Discrepancies are quantified by performing image differencing techniques on the rank order values of each map surface. We subsequently use the Gi*statistic to isolate regions where extreme differences occur. To assess similarities, a Gi*statistic is applied to both maps to locate spatially explicit areas of high cetacean density. Where clusters of high density values in both maps overlap we infer higher confidence that the datasets are representing a true ecological signal, while areas of difference we recommend as targeted locations for future sampling effort. We contextualize map similarities and differences using a dataset of human activity in the form of cumulative human effect scores. Overall, our analytical approach integrates novel spatial datasets from systematic surveys, citizen science, and remote sensing to provide updated information on cetacean distributions in BC. Our study generates geographic data products that fill knowledge gaps and results provide baseline information valuable for future decision-making. The methodology applied in this study can be generalized across species and locations to support spatial planning and conservation prioritization in both marine and terrestrial contexts. / Graduate / 2017-11-13

Dubbed the "most murderous" and "deadliest" city in the United States during 2006, 2007 and 2008, New Orleans has wrestled with crime and murder since its founding in 1718. Following Hurricane Katrina the city saw an increase in the murder rate despite a sharp decrease in population. The focus of this project was to map homicide data trends in the city of New Orleans over a period of seven years, 2002 to 2008, and compare spatial and temporal patterns via GIS. NOPD homicide location data were geocoded and analyzed in ESRI's ArcGIS geospatial software. Methodologies of hotspot detection included point maps, choropleth graduated color maps, and quartic kernel density maps. The project's goal was to not only detect hotspots, but to create a synoptic view of shifting homicide trends throughout the city of New Orleans, highlighting the impact of Hurricane Katrina.

Le segment 16°N de la dorsale Est-Pacifique (EPR) interagit avec le point chaud des Mathématiciens (PCM). A partir de l’analyse géochimique de 120 échantillons de verres basaltiques prélevés par submersible Nautile (campagne à la mer PARISUB 2010) coulée par coulée, ce travail présente une étude à très petite échelle de l’hétérogénéité chimique du manteau sous quelques kilomètres de dorsale (15°37’N et 15°47’N). Les résultats obtenus témoignent d’une variabilité géochimique jamais observée à si petite échelle sous une dorsale. Le degré d’hétérogénéité du manteau dans cette zone est comparable à celui de l’ensemble de l’EPR. Cette diversité est le produit du mélange entre trois sources mantelliques principales, caractérisant l’influence et l’hétérogénéité du point chaud. La densité de l’échantillonnage offre une résolution spatiale en adéquation avec les données bathymétriques, ce qui a permis de coupler les deux approches et faire une reconstruction spatio-temporelle de l’évolution géochimique et morphologique du système EPR/PCM.Celle-ci commence il y a environ 600 ka par le gonflement du segment et un changement général dans la composition du manteau ambiant, suivi de deux sauts d’axe successifs en direction de la chaîne il y a 250 et 150 ka. Lors de cette phase de rapprochement de nouvelles signatures géochimiques émergent ponctuellement dans les MORB. Parmi elles,une signature relique de manteau appauvri régional, une autre d’hétérogénéité enrichie locale, et enfin celle de deux types d’hétérogénéités contenues dans la source du PCM.Cette dernière, n’apparaît dans les MORB qu’au cours des 100 dernières années autour de 15°44’N, et constitue une signature géochimique inédite pour des MORB. Ce nouveau composant a la particularité d’avoir du Pb très peu radiogénique ("Unradiogenic Lead Component", ULC) associé à des signatures isotopiques en Sr, Nd et Hf enrichies.Les compositions en éléments majeurs, traces et isotopes (Sr, Nd, Hf, Pb et He) suggèrent l’implication de matériel métagabbroique, ancien (>2Ga) à affinité continentale.La présence de sulfures dans la source permettrait d’expliquer le Pb peu radiogénique.Le recyclage dans le manteau supérieur de pyroxénites à sulfures, provenant de la partie profonde d’anciens arcs continentaux permettrait d’expliquer l’origine de ULC. Les basaltes ULC seraient donc les témoins volcaniques de la fusion de ce réservoir discret qui contribue à résoudre le paradoxe du Pb. / 120 Mid-Ocean-Ridge basaltic (MORB) glasses were collected on discrete lava flow (~200m sampling interval) during submersible dives along the East-Pacific-Rise (EPR), between 15°37’N and 14°47’N, precisely where the ridge intersects the Mathematicianshotspot track. The data display a geochemical variability that has never been observedalong a ridge at such a small spatial scale. The range of isotopic compositions along this 15 km segment is commensurable to that of the entire EPR. It can be accounted for by a mixture of three main components, representative of the hotspot heterogeneity.The dense sampling, along and across the ridge segment, matches the resolution of themicro-bathymetric data, which made the spatio-temporal reconstruction of the geochemical and morphological evolution of the EPR/Mathematician hotspot system possible.The latest starts 600 kya with the segment inflation and a global change in the ambient mantle composition, followed by two successive jumps of the ridge axis (250 and 150 kya) towards the seamounts chain. During this phase as the two systems are getting closer,new geochemical signatures emerge in MORB. Among them, relics of regional depleted mantle, small enriched local heterogeneities, and two types of heterogeneities belonging to the hotspot source. The last one become apparent only during the last 100 yearsaround 15°44’N, and constitutes a novel geochemical signature for MORB. This new component’s most noticeable property is its very unradiogenic Pb ("Unradiogenic Lead Component", ULC) associated with mostly enriched Sr, Nd and Hf isotopic signatures. Putted together, major, trace elements and isotopes (Sr, Nd, Hf, Pb and He) suggest anancient (>2Ga) lower continental metagabbroic origin for this material, while the involvement of sulfides is considered in order to explain the unradiogenic lead compositions. Overall, the preferred model for the formation of ULC is the recycling within the uppermantle of sulfide bearing pyroxenites coming from continental arc roots. ULC-influenced basalts represent magmatic witnesses of the melting of this cryptic reservoir that can contribute to solve the Pb paradox.