Les cellules déficientes pour la recombinaison homologue (RH) présentent un ralentissement des fourches de réplication, un nombre aberrant de centrosomes et une aneuploïdie même en absence de stress exogène (Bertrand P 2003, Daboussi F 2005, 2008, Deng 1999, 2002, Griffin 2000, Kraakman-van der Zwet 2002). De plus, la fréquence des mitoses présentant des chromosomes surnuméraires est plus élevée dans ces cellules.L’ensemble des ces résultats suggéraient que le ralentissement des fourches de réplication dans les cellules déficientes pour la RH pourrait avoir un impact direct sur la formation de centrosomes surnuméraires. De plus, nous voulions savoir si cela pouvait également influencer la ségrégation des chromosomes au cours de la mitose. Les résultats que nous avons obtenus sont rassemblés dans l’article intitulé : “Homologous Recombination protects against mitotic defects and unbalanced chromosome segregation caused by spontaneous replication stress”.Le traitement des cellules compétentes pour la RH avec 5µM d’hydroxyurée (HU), un inhibiteur de l’enzyme de synthèse des dNTPs, induit un ralentissement des fourches de réplication parfaitement comparable à celui observé dans les cellules déficientes pour la RH. Après traitement à l’HU des cellules compétentes pour la RH, la fréquence de mitoses présentant des chromosomes surnuméraires augmente et devient similaire à la fréquence de mitoses avec des chromosomes surnuméraires pour les cellules déficientes pour la HR non traitées à l’HU. Nous avons mesuré l’impact de l’HU sur l’apparition des ponts anaphasiques et sur des défauts de ségrégation des chromosomes lors de la mitose. En l’absence de traitement, nous observons une fréquence plus élevée de ponts anaphasiques et de défauts de ségrégation dans des cellules déficientes pour la RH. Des traitements avec 5µM d’HU augmentent la fréquence des ponts anaphasiques et des erreurs de ségrégation dans les cellules compétentes pour la RH, pour atteindre un niveau comparable aux cellules déficientes pour la RH. Ainsi, une altération de la dynamique de réplication consécutive à une déficience de RH ou à un traitment avec de faibles doses d’HU induit des défauts au cours de la mitose. Un lien direct entre une dynamique de réplication anormale et l’apparition d’un nombre aberrant de centrosomes pourrait être la persistance en mitose d’ADN non répliqué ou endommagé.  Comme l’ADN non répliqué ou les fourches bloquées induisent la formation d’ADN simple brin couvert par RPA, nous avons compté le nombre de cellules en G2/M présentant des foyers de RPA, et observé que la fraction de cellules ayant plus de 5 foyers de RPA augmente dans des cellules déficientes pour Brca2. En conclusion, nous proposons un lien direct entre des altérations de la cinétique de réplication, l’apparition de centrosomes surnuméraires et des défauts de ségrégation des chromosomes en mitose dans les cellules déficientes pour la RH même non soumises à un stress exogène. L’utilisation de faibles doses d’HU dans des cellules compétentes pour la RH mime les phénotypes observés dans les cellules déficientes pour la RH et confirme notre modèle.Nous avons également cherché à comprendre les causes du ralentissement des fourches de réplication observé dans les cellules déficientes pour la RH. Il est ainsi possible que les arrêts de fourches spontanés soient une conséquence d’un stress oxydatif endogène. Dans les cellules compétentes pour la RH, le redémarrage des fourches bloquées est possible et assure une progression normale de la réplication de l’ADN. Ceci favorise une ségrégation équilibrée des chromosomes, le maintien de la diploïdie et la stabilité du génome. Dans des cellules déficientes pour la RH, les blocages de fourches devraient être délétères puisque les principaux mécanismes de redémarrage des fourches ne sont pas fonctionnels. De plus, l’arrêt prolongé des fourches ainsi que les cassures double brin générées par l’effondrement des fourches devraient activer des voies de signalisation. Nous avons néanmoins observé que les cellules ne sont pas bloquées dans le cycle cellulaire, ce qui suggère qu’un seuil supérieur de dommages doive être atteint pour induire l’arrêt du cycle. Les stress endogènes ne semblent donc pas suffisamment élevés pour atteindre ce seuil : même si l’ensemble des fourches parcourant le génome sont ralenties, l’activation d’origines cryptiques permet de compenser et ainsi de maintenir la progression dans le cycle. Mais puisque les cellules ne sont pas arrêtées dans le cycle, des fourches bloquées, de l’ADN endommagé ou non répliqué pourraient persister jusqu’à la transition G2/M et in fine perturber le déroulement de la mitose. Des centrosomes multipolaires provoquent la formation de fuseaux multipolaires et favorisent la ségrégation déséquilibrée des chromosomes, entraînant l’aneuploïdie, la déstabilisation du génome et le développement de cancers. / HR deficient cells show slow replication kinetics, aberrant centrosome number and aneuploidy even in the absence of any exogenous stress (Bertrand P 2003, Daboussi F 2005, 2008, Deng 1999, 2002, Griffin 2000, Kraakman-van der Zwet 2002). Frequency of mitosis with extra centrosomes is elevated and replication kinetics decreased in HR deficient compared to HR proficient cells, in the absence of exogenous stress. Thus the question arose, if replication slowing down in HR deficient cells has direct impact on the appearance of supernumerary centrosomes. Furthermore we wanted to know if this might directly impact chromosome segregation. The results we gained are brought together in the paper “Homologous recombination suppression causes spontaneous mitotic alterations through endogenous replication stress”. By treating our HR proficient cells with 5µM HU we found the perfect concentration to mimic replication dynamics of HR deficient cells in an HR proficient background. This concentration was applied to HR proficient cells. After HU treatment the frequency of mitosis with extra centrosomes was elevated in HR proficient cells. Now they showed the same frequency of mitosis with extra centrosomes, than unchallenged HR deficient cells. We measured the impact of HU treatment on occurrence of anaphase bridges or aberrant mitotic segregation. In the absence of treatment higher frequency of anaphase bridges and aberrant mitotic segregation was detected for HR deficient cells. With 5µM HU the frequency of anaphase bridges and aberrant mitosis could be elevated in HR proficient cells. Now they showed aberrant mitotic features with the same frequency than unchallenged HR deficient cells. A direct link between abnormal replication kinetics and aberrant centrosomes might be unreplicated or damaged DNA, that enter mitosis. Unreplicated or blocked DNA might harbour ss DNA bound RPA. Thus we counted G2/M cells with RPA foci. Indeed the fraction of cells that harbour more than 5 RPA foci was elevated in Brca2 deficient in comparison to Brca2 proficient cells. In conclusion we propose a direct link between delayed replication, supernumerary centrosomes and aberrant chromosome segregation in unchallenged HR deficient cells. If we mimicked replication kinetics of HR deficient cells in an HR proficient background, we also mimicked frequency of mitosis with extra centrosome number and aberrant chromosome segregation. Furthermore we investigated the causes of replication slowing down in HR deficient cells. It can be hypothesized that endogenous oxidative stress is implicated in spontaneous fork arrest. In HR proficient cells, reactivation of stalled replication forks and therefore normal replication progression is assured. This favours balanced chromosome segregation, diploidy and genetic stability.In HR deficient cells, replication fork blockage might be detrimental as the main restart mechanism for blocked forks is absent. Prolonged fork blockage or DSB’s arising by fork collapse or resolution of blocked replication forks might activate signalling pathways. However cells are not arrested in cell cycle progression, suggesting that a threshold should be reached to activate cell cycle arrest. Endogenous stress is not sufficient high to reach this threshold. Replication is genome wide slowed down. In this context, the activation of cryptic origins compensates at least partly the slow replication velocity. However, because cells were not arrested in cell cycle progression, some blocked replication forks and damaged or unreplicated DNA regions might persist until G2/M phase and affect centrosome duplication and chromosome segregation. Multipolar centrosomes cause multipolar spindles and favour unbalanced chromosome segregation leading to aneuploidy, genetic instability and cancer development.

No description available.

No description available.

No description available.

No description available.

Detta examensarbete har haft som mål att undersöka tjällyftningen hos en väg i en fältstudie och utvärdera reliabiliteten hos två olika modeller för skattning av tjällyftning. Modellerna som har studerats är Trafikverkets nuvarande, vilken är implementerad i deras vägdimensioneringsverktyg PMS Objekt, samt segregation potential theory. Den studerade vägsträckan är belägen i Kiruna. I vägen har borrkärneprover tagits och vägens obundna lager, inklusive terassmaterial, har blivit analyserade i laboratorium. Dessa tester inkluderar både geoteknisk klassificering och endimensionella frysförsök på terassmaterialet. Materialets tjälfarlighet har klassificerats enligt både Trafikverkets eget och det amerikanska USACEs system. Alla prover, inklusive terrassmaterialet, består huvudsakligen av grus och sand. Enligt båda de använda klassificeringssystemen bedöms alla prover som icke tjälfarliga. Nivåmätningar utförda på vägen visar dock att tjällyftning ändå förekommer i vägen. Denna tjällyftning har inte kunnat modelleras framgångsrikt i PMS Objekt, där ingen tjällyftning alls fås trots att en dimensionerande vinter tillämpas i analysen. Däremot har en god överensstämmelse mellan bakåträknad och empiriskt beräknad tjälfarlighetsklassificering med SP0-värde enligt segregation potential theory kunnat ses. Även när detta beräknas utifrån utförda frysförsök fås en relativt god överensstämmelse. Studiens främsta fynd är att den visar på att även material som bedöms som ej tjällyftande enligt de två systemen för tjälfarlighetsklassificering faktiskt orsakar tjällyftning och att detta omfattar både terrass- och överbyggnadsmaterial. Studien visar att detta tjällyft främst beror på primärt lyft, varför klassificeringarna stämmer ganska väl om endast det sekundära lyftet avses. Studien har även visat på att Trafikverkets nuvarande modell är otillräcklig när det kommer till att modellera tjällyftning för grovkorniga jordar. Slutligen har studien även visat på möjligheten att bedöma jords tjälfarlighet med hjälp av segregation potential theory, även om också denna metod endast kan användas för att modellera sekundärt lyft. / The aim of the master thesis has been to examine the frost heaving of a road in a field study and to evaluate the reliability of two different models for estimation of frost heaving. The studied models are the current one of the Swedish Transport Administration, which is implemented in their road design tool PMS Objekt, and the segregation potential theory. The studied road section is located in Kiruna, in the northern part of Sweden. The road has been cored and the unbound layers of it, including the subgrade, have been analyzed in laboratory. These analyses include both geotechnical characterization and one-dimensional frost heave tests of the subgrade material. The frost susceptibility of the collected material has been classified according to both the Swedish Transport Administrations system and the American USACE’s system. All samples, including the subgrade, consist mainly of gravel and sand. According to both the used classification systems all samples are classified as not frost susceptible. However, the elevation measurements of the road show that frost heaving occurs in it despite this. This heaving has not been possible to model successfully in the program PMS Objekt. In it the frost heave prediction yields no heave at all, despite applying a design winter (worst case) in the analysis. A good conformity has however been observed between back-calculated and empirically evaluated frost susceptibility using segregation potential theory. A quite good conformity has also been observed when the same thing is evaluated from the preformed freeze tests. The most important finding of the study is that even material that is categorized as non-frost susceptible according to the two studied systems actually does heave. This finding includes both subgrade aswell as the unbound material in the superstructure. It has been found that the total frost heave observed in this study originates mainly from primary heaving, meaning the studied systems are quite correct in their frost susceptibility classification if only secondary heaving is intended. The study has also shown that the current model applied in PMS Objekt is poor in predicting the amount of heaving in coarse subgrades. Finally, the study has also shown the possibility to evaluate a soils frost susceptibility using segregation potential theory, although this model aswell is only applicable to secondary heave

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The socioeconomic transformations that occurred in the 90s in Brazil resulted in the redefinition of a new spatial pattern in Brazilian cities. This new standard fragmented approaches physically different social groups, but keeps them socially distant. The residential segregation, separation of families belonging to different social groups, can be analyzed from the degree of clustering, exposure and spatial isolation of a social group in certain places of the urban space. In this sense, segregation measures are useful tools for the analysis of patterns, causes and consequences of this phenomenon. Thus the aim of this study was to identify and analyze the pattern of residential segregation existing in the Urban Space Santa Maria - RS, in 2010. In fulfilling this objective the study supports the referential theoretical, emphasizing the themes that involve residential segregation, its measurement and geotechnology; methodological philosophical determined Analytical and Hypothetical-Deductive, and technician determined by the use of geotechnology and quantitative techniques. From the assumptions and considerations raised formulated was possible to know the reality of the Urban Space in Santa Maria-RS, with respect to residential segregation, noting that although this process to focus on certain regions and sectors, there is physical proximity (integration) social classes, without which this translates into social proximity (interaction). And that in areas where there is greater integration, the same occurs with individuals of similar social classes. In this sense, the methodology proved effective in identifying areas segregated and economic groups that composed it. / As transformações socioeconômicas ocorridas nos anos 1990 no Brasil tiveram como consequência a redefinição de um novo padrão espacial nas cidades brasileiras. Esse novo padrão fragmentado aproxima fisicamente diferentes grupos sociais, porém os mantém distantes socialmente. A segregação residencial, a separação entre famílias pertencentes a distintos grupos sociais, pode ser analisada a partir do grau de agrupamento, exposição e isolamento espacial de um grupo social em determinados locais do espaço urbano. Neste sentido, medidas de segregação são ferramentas úteis para a análise de padrões, causas e consequências deste fenômeno. Assim, o objetivo deste trabalho foi identificar e analisar o padrão de segregação residencial vigente no Espaço Urbano de Santa Maria RS, no ano de 2010. No cumprimento deste objetivo, o estudo se ampara nos referenciais: teórico, ao enfatizar as temáticas que envolvem a segregação residencial, sua mensuração e as geotecnologias; metodológico-filosófico, pelo determinado Analítico e Hipotético-Dedutivo; e técnico, determinado pelo uso das geotecnologias e técnicas quantitativas. A partir dos pressupostos levantados e das considerações formuladas foi possível conhecer a realidade do Espaço Urbano de Santa Maria, RS, no que diz respeito à segregação residencial, verificando que apesar de este processo se concentrar em algumas regiões e setores, há proximidade física (integração) das classes sociais, sem que isto se traduza em proximidade social (interação). E que nas áreas onde há maior integração, a mesma ocorre com indivíduos de classes sociais semelhantes. Neste sentido, a metodologia aplicada por técnicas matemáticas e de geoprocessamento mostrou-se eficiente na identificação das áreas segregadas e dos grupos econômicos que a compõem.

Where people choose to live is a consequence of a variety of factors, such as housing cost, design, localization and personal considerations. Urban blue spaces provide a range of perceived benefits to nearby inhabitants and is generally seen as attractive traits for an area, influencing housing cost and demographics amongst other things. This has implications for socioeconomic spatial distribution, and thus the city could also be viewed as a map of socioeconomic variation. This paper seeks to examine the socioeconomic spatial variation in the city of Karlstad in relation to urban blue spaces. Using publicly available statistics for 23 different areas of the city, this variation is visualised in a series of maps and tables. Two models, one using average income and one using a proposed local socioeconomic index, are devised and used to estimate the impact of blue spaces on socioeconomic spatial variation in Karlstad. Results show a significant socioeconomic variation between different areas. Certain areas score high and certain areas score low in every category of the socioeconomic index, painting the picture of a socioeconomically divided city. The models used are proven to be inaccurate. Although the four areas with the lowest average income are all located in zones furthest from blue spaces, no evidence indicate that high and medium high average income areas, nor areas with high socioeconomic index, generally are located in closer proximity to blue spaces. Findings imply that socioeconomic spatial variation in Karlstad cannot be reduced to blue spaces and is a complex area of further research.

Usando a generalização de Grauwin et al. [Ref. 3] do modelo de segregação de Schelling foi possível estudar, em um modelo simplificado, as consequências da guerra fiscal travada entre os estados de uma federação e os resultados da chamada guerra da taxa que os bancos adotaram depois de implantada a portabilidade de crédito bancário. No modelo de Grauwin a cidade é dividida em Q quarteirões e todos os quarteirões possuem a mesma função utilidade dependente da densidade u(m,?), que mede a satisfação dos agentes que ali residem. Inserimos um parâmetro de desordem m_b em um dos blocos para torná-lo mais atrativo que os demais. Ter um dos blocos diferente é a essência do modelo de guerra entre os quarteirões. Foi analisada uma aplicação deste modelo fazendo um paralelo com o cenário de uma guerra fiscal entre os estados de uma nação. Para tal, interpretamos os agentes econômicos como sendo as de indústrias (ou pessoas) que tomam decisões em busca de aumentar sua própria satisfação e os quarteirões como os estados de uma federação. A guerra fiscal é um instrumento usado por alguns estados brasileiros que reduzem impostos, cedem terrenos, fornecem infra-estrutura, etc para atrair investimentos na sua região. Esta guerra no primeiro momento pode ser benéfica para a sociedade, pois contribui para a descentralização da economia e reduz as diferenças de PIB e social entre os estados. Porém, em âmbito nacional, o embate econômico entre os estados geralmente resulta em perda de arrecadação para a nação. Um Estado totalmente desocupado, caso queira roubar empresas de Estados já consolidados, precisa dar muito mais incentivos para atrair investimento por conta da sua baixa população e consequentemente baixa utilidade. Neste trabalho tentamos quantificar os gastos que os Estados têm com este tipo de ação. Outra releitura dos resultados pode ser aplicada ao modelo de portabilidade de crédito, onde interpretamos os agentes econômicos de Grauwin como tomadores de empréstimo e os quarteirões como bancos de crédito ao varejo. A taxa de juros cobrada de cada banco dependerá do tamanho da carteira que este possui. Ter um banco com uma taxa de juros diferenciada o torna mais atrativo que os demais e este começa a roubar clientes dos outros bancos, contudo, o mercado reage e também reduz suas taxas, criando uma guerra da taxa no mercado financeiro. Estudando o cenário egoísta (onde o governo não desestimule a troca entre bancos) e supondo que a quantidade de tomadores no mercado seja suficientemente pequena, a dinâmica conduzirá a uma situação onde teremos apenas alguns bancos coexistindo e outros falindo. No limite egoísta o banco que se dispôs a dar incentivo terá a carteira maior que os demais bancos com taxas menores e isto vai ser invertendo à medida que o governo impõe comportamento mais altruísta da sociedade. Estudamos analiticamente os efeitos das variações da densidade e dos parâmetros (m) e altruísmo (a) no cenário global bem como os resultados esperados com a inserção de uma desordem (m_b) em um dos blocos. E por fim foram feitas simulações em computador para verificar se comportamento das dinâmicas em todos os cenários eram compatíveis com as soluções obtidas. / Using Grauwins generalization [Ref. 3] of Schelling\'s segregation model we study, in a simplified model, some consequences of the \"fiscal war\" waged between the states of a federation, and of the rate tax generated by the recent Brazilian Central Bank regulation of bank credit portability. In Grauwins model the city is divided into blocks and all blocks have the same utility function, which measures the satisfaction of agents living there and depends on the density of agents. We introduced a disorder parameter in one of the blocks to make it more attractive than the others, in order to mimick the essential igredient of competition between states or banks. We first analyze an application of this model in the scenario of a fiscal war between the states of a nation. We interpret blocks as the states of a federation and economic agents as the industries (or people) who make decisions seeking to increase their own satisfaction. The fiscal war is an instrument used by some Brazilian states consisting in reducing taxes, subsidize land, provide infrastructure, etc in order to attract investment. This war at first can be beneficial for society as it contributes to the decentralization of the economy and reduces the differences of GDP and social discrepancies between states. Nationwide, however, the economic struggle between states usually results in loss of revenue at the global level. A vacated state, in order to attract agents already established elsewhere, need to give more incentives to attract investment because of its low population and consequently low utility. In this work we try to quantify the costs that states have with this kind of action. Another analysis of the results can be applied to a bank credit portability model, where we interpret economic agents as customers and blocks as retail credit banks. The interest rate levied on each bank will depend on the size of the portfolio of that bank. Having a bank with a differentiated interest rate makes it more attractive than others, and it begins to \"steal\" customers from other banks.However, those react and also reduce their rates, creating a \"war tax\" in the financial market. Studying the selfish scenario (where the government doesnt discourage a client from taking his/her debt to another bank), and assuming that the number of customers in the market is sufficiently small, the dynamics leads to a situation where we have just a few coexisting banks, the others having gone bankrupt. In the selfish limit the bank that was willing to give encouragement will have the largest portfolio while offering lower interest rates than the others, but this will be reversed as the government imposes a more altruistic behavior to the clients. We study analytically the effects, at the global level, of variations in the density, in the altruism parameter and in the parameter determining the utility function at saturation, as well as the effects of introducing disorder in one or more blocks. Finally, computer simulations were performed to check that the dynamic behavior in all scenarios was consistent with those obtained solutions.

Aufgrund der sehr hohen magnetokristallinen Anisotropiekonstante eignet sich besonders die Phase SmCo5 für zukünftige Festplattenmedien mit hoher Speicherdichte. Durch die starke Oxidationsneigung und die gegebene chemischen Ähnlichkeit anderer Seltenen Erden ist es eine Herausforderung hartmagnetische SmCo-basierte Nanopartikel mittels Inertgaskondensation herzustellen. Zudem bestimmt die Oberflächenenergie maßgeblich die Eigenschaften von Nanopartikeln, sodass ein Element mit einer geringen solchen energetisch bevorzugt die Oberfläche bildet. Diese Arbeit zeigt auf, wie die sauerstoffbasierte Oxidation und die unterschiedlichen Oberflächenenergien der legierungsbildenden Elemente die Struktur, die Morphologie und die chemische Verteilung der Elemente innerhalb der Nanopartikel beeinflussen und so die Legierungsbildung einer hartmagnetischen Sm(Pr)Co-Phase steuern. Mithilfe von aberrationskorrigierter, hochauflösender Transmissionselektronenmikroskopie in Verbindung mit Elektronenenergieverlustspektroskopie werden Morphologie, Elementverteilung und Struktur von unterschiedlich hergestellten Sm(Pr)Co-Nanopartikeln untersucht und analysiert. Die auftretende Segregation der Seltenen Erden an die Oberfläche der Nanopartikel wird zum einen auf eine sauerstoffinduzierte, zum anderen auf eine intrinsische Segregation, also eine durch unterschiedliche Oberflächenenergien der legierungsbildenden Elementen hervorgerufene Segregation zurückgeführt. Anhand eines entwickelten geometrischen Modells wird zwischen den beiden Ursachen der Segregation unterschieden. Das Verständnis um die kausalen Zusammenhänge der Segregation lässt den Schritt zur Herstellung hartmagnetischer intermetallischer SmCo-basierter Nanopartikel zu. Hierzu werden speziell Nanopartikelagglomerate geformt und optisch in einem Lichtofen erhitzt, sodass die Primärpartikel in den Agglomeraten versintern und schließlich das resultierende sphärische Partikel kristallisiert. HRTEM-Aufnahmen und Elektronenbeugung bestätigen die erfolgreiche Herstellung von SmCo5- und Sm2Co17-basierten Nanopartikeln. Die Koerzitivfeldstärke dieser Partikelensembles beträgt 1,8T und einem Maximum in der Schaltfeldverteilung bei 3,6T. Die magnetischen Eigenschaften spiegeln die analysierten strukturellen, morphologischen und chemischen Eigenschaften der Nanopartikel wider.