Made available in DSpace on 2014-12-17T14:57:46Z (GMT). No. of bitstreams: 1 JoseCCSJ.pdf: 1343903 bytes, checksum: aa2a5fbffd13b95d16ec1f429e355eb5 (MD5) Previous issue date: 2008-08-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The industries of structural ceramics are among the most important production chains in the state of Rio Grande do Norte. The industry and other interest groups to target the replacement of firewood by natural gas. Studies accordingly concluded that simple change does not guarantee products of superior quality, and that the increase in spending on fuel can economically cripple the use of gas for burning the majority of products manufactured by that action. However some proposals of innovations in terms of process and product are being studied in an attempt to justify the use of natural gas in industry, structural ceramics. One of the aspects investigated is the development of ceramic products differentiated, with new designs and greater value added. Inserted in that context, this paper aims to investigate the potential use of clay-firing clear fabrication of the "bricks of apparent joins drought", a new ceramic product with an innovative way. The development of the work was done in three stages. In the initial stage was held the characterization of raw materials, sought information on physical, chemical, mineralogical and mechanical samples. In the second stage five bodies were made using two of the nine ceramic clay characterized the first step. The masses were analyzed and compared with respect to the size distribution, plasticity and technological properties. In the last part of this work was carried out tests on massive bricks manufactured on an industrial scale. The results show that the nine clays can be used in the manufacture of new ceramic products, is the only constituent of mass ceramic or by mixing with other(s) clay(s / As ind?strias de cer?mica estrutural figuram entre as cadeias produtivas mais importantes do estado do Rio Grande do Norte. O setor e outros grupos de interesse almejam a substitui??o da lenha pelo g?s natural. Estudos realizados nesse sentido conclu?ram que a simples mudan?a n?o garante produtos de qualidade superior, e que o aumento no gasto com combust?vel pode inviabilizar economicamente o uso do g?s para queima da maioria dos produtos fabricados por esse seguimento. Entretanto algumas propostas de inova??es em termos de processo e produto v?m sendo estudadas na tentativa de justificar o uso do g?s natural na ind?stria de cer?mica estrutural. Uma das vertentes pesquisadas ? o desenvolvimento de produtos cer?micos diferenciados, com novos designs e maior valor agregado. Inserido nesse contexto, o presente trabalho tem como objetivo investigar a potencialidade do uso de argilas de queima clara para fabrica??o dos tijolos de junta seca , um novo produto cer?mico com forma inovadora. O desenvolvimento do trabalho foi efetuado em tr?s etapas. Na etapa inicial foi realizada a caracteriza??o das mat?rias-primas, buscando obter informa??es em rela??o ?s propriedades f?sicas, qu?micas, mineral?gicas e mec?nicas das amostras. Na segunda etapa foram formuladas cinco massas cer?micas utilizando duas das nove argilas caracterizadas na primeira etapa. As massas foram analisadas e comparadas em rela??o ? distribui??o granulometria, plasticidade e propriedades tecnol?gicas. Na ?ltima parte desse trabalho foi realizado testes em tijolos maci?os fabricados em escala industrial. Os resultados mostram que as nove argilas podem ser utilizadas na fabrica??o dos novos produtos cer?micos, seja como ?nica constituinte da massa cer?mica ou pela mistura com outra(s) argila(s)

A Síndrome de von Hippel-Lindau é uma doença hereditária multissistêmica, causada por mutações germinativas no gene VHL que predispõe o portador a manifestações benignas e malignas em diversos órgãos. Entre esses eventos, o carcinoma de células claras renais (CRC) é o de pior prognóstico, com uma penetração média de 25% e sendo a principal causa de morte nestes pacientes. Os CRCs são tumores agressivos, pouco responsivos à quimioterapia e imunoterapia, e muitas vezes são diagnosticados em estágios avançados. Podem estar associados a síndromes hereditárias como o VHL ou apresentar a forma esporádica. Caracteristicamente, o CRC é provocado pela inativação dos dois alelos do gene VHL. Nos casos associados ao VHL, um alelo do gene VHL sofre uma mutação germinativa e um segundo evento mutacional somático nas células do tumor. Por outro lado, na forma esporádica, o CRC é resultado de dois eventos somáticos adquiridos, que incluem uma combinação de metilação do promotor, mutações pontuais que afetam a sequência de leitura aberta (ORF) e rearranjos cromossômicos, principalmente perda de heterozigosidade (LOH). Embora os eventos somáticos nos CRCs esporádicos já tenham sido explorados em outros estudos, os mecanismos de inativação somáticos do gene VHL nos CRCs associados à síndrome ainda não foram bem descritos. Este estudo avaliou os eventos somáticos no gene VHL em CRCs retirados em procedimentos cirúrgicos de pacientes portadores da síndrome. Os eventos somáticos em vários tumores de um mesmo paciente foram comparados a fim de verificarmos se essas mutações são independentes e não clonais. Oito pacientes com amostras CRCs previamente armazenadas no BNT tiveram sua mutação germinativa no gene VHL caracterizada por sequenciamento ou MLPA. Todas as amostras foram submetidas a uma revisão da patologia e macrodissecadas sempre que necessário. Para a análise das manifestações somáticas do gene VHL, o DNA foi extraído de 30 CRCs conservados em RNA latter ou formaldeído (parafina). As amostras foram analisadas quanto à metilação da região promotora do gene pelo método MS-PCR e para mutações pontuais por sequenciamento. Fomos capazes de detectar a mutação somática em 25 dos 30 tumores, incluindo uma mutação pontual e dois tumores diferentes de um mesmo paciente, nenhuma microdeleção e 23 grandes deleções. Em contraste com a literatura, nenhum dos tumores apresentou metilação no promotor do VHL. Devido ao grande número de achados LOH e da resolução limitada da técnica de MLPA para avaliar a extensão dos rearranjos cromossômicos em 3p, não foi possível concluir a análise de clonalidade dos tumores. Um estudo exploratório para caracterizar ganhos e perdas genômicas utilizando a técnica CNV array está em andamento em nosso laboratório. / The von Hippel-Lindau syndrome (VHL) is a multissystemic hereditary disease, caused by germline mutations in the VHL gene that predisposes the carrier to benign and malignant manifestations in different organs. Among these events, the clear cell renal carcinoma (RCC) is the most fearful, with an average penetration of 25% being the leading cause of death in these patients. RCCs are aggressive tumors, poorly responsive to chemo- and immunotherapy that are often diagnosed in advanced stages. They can be associated with hereditary syndromes such as VHL or present in a sporadic form. Characteristically, RCCs carrier the inactivation of the two alleles of VHL gene. In cases associated with VHL, one allele of the VHL gene is mutated in the germline, and the second mutational event occurs in the somatic cells of the tumor. On the other hand, in the sporadic form, RCCs results of two acquired somatic events, which includes a combination of methylation of the promoter, point mutations affecting the ORF, and rearrangements mainly loss of heterozigosity (LOH). Although somatic events in sporadic RCC have been explored before by others, the mechanisms of somatic VHL gene inactivation in VHL-associated RCCs have been poorly characterized. This study evaluated the somatic mutational events in the VHL gene of RCCs removed from VHL patients in therapeutic surgical procedures. The somatic events in multiple tumors from the same patient were compared in order to analyze whether these mutations are independent and not clonal. Eight patients with RCCs samples previously stored at BNT had their germline VHL gene mutation characterized by sequencing or MLPA. All samples were submitted to a pathology review and macrodissected whenever necessary. For the analysis of somatic events of VHL gene, DNA from 30 RCCs were extracted from either RNA later or archival formalin-fixed, paraffin-embedded tissue sections. Samples were analyzed for VHL gene promoter methylation by MS-PCR, and for point mutation in the coding DNA by sequencing. We were able to detect the somatic mutation in 25 of the 30 tumors, including one point mutations in two different tumors of the same patient, no micro-deletions, and 23 large deletions. In contrast to the literature, none of the tumors have shown methylation on the VHL promoter. Because of the large number of LOH findings, and the limited resolution of MLPA to evaluate the extension of 3p chromosomal rearrangements, we could not conclude the analysis of tumor clonality. An exploratory study to characterize genomic gains and losses using CNV-array technique are ongoing in our laboratory.

Introdução: com o uso generalizado de métodos de imagem, aumentou-se a detecção de lesões renais como achados incidentais. Tais lesões podem ser tanto benignas, tais como os angiomiolipomas, e outras malignas, como os carcinomas de células renais, portanto torna-se importante um método não-invasivo com boa acurácia para sua distinção . A ultrassonografia é pouco específica para este fim. A tomografia computadorizada e a ressonância magnética são os métodos mais utilizados na caracterização de lesões incidentais renais. Na Ressonância Magnética, o uso de sequências convencionais ponderadas em T2W e T1W, antes e após a administração endovenosa de contraste paramagnético, mostrou-se pouco eficaz para este fim. Técnicas quantitativas associadas às imagens convencionais, tais como a oposição de fase e a restrição a difusão da água, vêm sendo estudadas, devido ao potencial para melhorar a caracterização não-invasiva, evitando nefrectomias parciais ou totais, e outras intervenções invasivas por lesões benignas. Objetivos: avaliar a acuidade diagnóstica de técnicas combinadas de ressonância magnética para diferenciação de angiomiolipomas pobres em gordura de lesões malignas do rim. Métodos: pacientes que obtiveram o diagnóstico histológico das lesões renais entre os anos de 2010 e 2014 e que realizaram exame pré-operatório. As lesões foram estudadas, colocando-se um ROI (region of interest, no inglês) na maior parte da lesão e córtex renal normal, evitando-se área de não-lesões, calculando a intensidade de sinal nas seqüências T1W in e out-phase, T2W, o Wash in, Wash out relativo e absoluto das lesões e o cálculo absoluto do sinal da lesão no ADC (coeficiente de difusão aparente, do inglês). Os resultados foram obtidos na forma de índices padronizados pelo córtex renal e baço, pelas fases pré e pós-contraste, e de forma absoluta pelo ADC. Os resultados foram confrontados com o diagnóstico final e feito associações estatísticas para observar a relevância. Resultados:Foram estudadas 85 lesões em 74 pacientes, sendo 40 do gênero masculino e 34 do feminino. O cálculo do teor de gordura se mostrou ineficaz para distinção entre CCRs e AMLpg; o índice de intensidade de sinal em T2W, lesão/córtex normal foi útil na diferenciação dos CCRs CC de AMLpg. Outro parâmetro importante foi a cálculo de wash out relativo que se mostrou mais acentuado no AMLpg que em todos os subtipos de CCRs estudados e da medida do ADC médio, que apresentou valores maiores nos casos de CCR CC, em comparação com os outros subtipos e com os AMLpg. Conclusão: As técnicas combinadas de RM, principalmente o índice de sinal T2W da lesão, Wash out relativo e IS do ADC, associados a dados epidemiológicos são viáveis, quando utilizados em conjunto, para a diferenciação de lesões malignas renais dos angiomiolipomas, podendo ter implicações na conduta terapêutica, com redução do número de nefrectomias por lesão benignas. / Introduction: With the widespread use of imaging methods, detection of incidental renal masses has steadily increased in recent years, and these may be either benign, such as angiomyolipoma, or malignant, such as renal cell carcinomas. Therefore, it is important to have a method that allows accurate characterization. Ultrassonography is not very specific for this purpose. CT and MRI are the methods used in the characterization of renal incidental lesions. In MRI, the use of conventional sequences, such as T1W and T2W before and after intravenous administration of paramagnetic contrast media, has proved ineffective for this purpose. Quantitative techniques associated with conventional images, such as chemical shift and diffusion weighted imaging (DWI), have played a key role in this differentiation, which aims to improve characterization, avoiding partial or total nephrectomy, and other invasive interventions for benign lesions. Objectives: to evaluate the diagnostic accuracy of combined techniques of MRI to differentiate fat-poor angiomyolipoma from renal cell carcinomas. Methods: Patients who had a histological diagnosis of renal lesions between 2010 and 2014 and underwent pre-operative exam. An ROI (region of interest)cwas placed in most of the lesion and normal renal cortex, avoiding area of non lesions, by calculating the signal intensity in all sequences, in and out phase T1W, T2W, and the wash in, wash out, relative and absolute, of the lesions and estimation of the ADC. The results were obtained in the form of standardized indices for renal cortex and spleen, the pre- and post-contrast phases, and absolute values for ADC. Results were confronted with the final diagnosis and statistical analysis to observe the relevancy. Results: the estimation of intracellular fat content was ineffective for characterization, while the T2W signal intensity index was used for differentiation between CCRs clear cells from fat-poor AML. Another important parameter was the \"wash out\", which was more prominent for AMLpg. ADC values was higher for CCR CC. Conclusion: We concluded that the combined techniques of MRI mainly T2W signal ratio, \"Wash out\" and ADC values, when used in association and correlated with epidemiological data may be feasible for the differentiation among fat-poor angiomyolipomas and renal malignancies, with important therapeutics implications, reducing unnecessary nephrectomies for benign lesions.

The aim of this thesis was to test and evaluate whether parameter regionalization of a hydrological model can be used to model the impact of forest clearcutting on streamflow in Sweden. This is an important task to be able to perform water management and impact assessments adequately. The HBV conceptual rainfall-runoff model was applied for 218 Swedish catchments of different sizes that were spread across the country and covered a wide range of different forest cover percentages. The modelling approach included calibration of the model for each catchment using a genetic algorithm and then associating the resulting optimal parameter values with the percentage of forest cover. The obtained relationship between different model parameters and forest cover was validated with help of a paired catchment study site in northern Sweden where a clear cut was done in 2006: calibrated optimal parameter sets of pre- and post-clearcutting conditions were compared to parameter sets obtained from the Sweden-wide analysis. Correlations were found for about half of the fifteen hydrological model parameters, but the validation with the paired catchment study site could only partially confirm these obtained relationships. The results suggest that the adopted parameter regionalization approach is too basic. However, some of the results seem promising and emphasize the need for further research and development of the approach to provide a more reasonable method to model the impact of forest clearcutting on streamflow. / Det huvudsakliga målet med detta examensarbete var att testa och utvärdera om parameterregionalisering av en hydrologisk modell kan vara en lämplig metod för att modellera och kvantifiera påverkan från skogsavverkning på vattenbalansen i Sverige. Detta är en viktig uppgift för att kunna hantera våra vattenresurser och utföra konsekvensanalyser på ett tillfredsställande sätt. En konceptuell hydrologisk modell tillämpades på 218 avrinningsområden av olika storlekar och som var geografiskt utspridda i hela Sverige där även andelen skog i avrinningsområdena hade ett brett spektrum. Den använda modelleringsmetoden innefattade kalibrering av varje avrinningsområde genom att använda en genetisk algoritm, varefter de optimala parametervärdeana korrelerades mot andelen skog i avrinningsområdet. Idén med denna metod är att använda dessa potentiella samband för att justera modellparametrarna och därmed simulera en skogsavverkning. De erhållna sambanden mellan modellparametrarna och skogstäcket validerades med hjälp av data från en försöksstudie i norra Sverige där en skogsavverkning gjordes under 2006. Skillnaden mellan de bäst fungerande parametervärdena före och efter skogsavverkningen jämfördes med de tidigare sambanden från andra avrinningsområden i Sverige. Signifikant korrelation hittades för ungefär hälften av de 15 hydrologiska modellparametrarna, men valideringen mot den riktiga skogsavverkningen kunde bara delvis bekräfta de erhållna sambanden. Resultaten visar att detta sätt att använda parameterregionalisering antagligen är för grundläggande. Vissa resultat är ändå lovande och fortsatt forskning och utvidgning av metoden är nödvändig för att kunna tillhandahålla en rimlig metod för att kvantifiera en skogsavverknings effekter på vattenbalansen.

Communication technology allows companies to deliver services electronically. This leads to a lower dependence on geographical location. Historically, companies have moved IT related work to countries where wages are lower to decrees costs. When IT systems over time increases in complexity, competence and resource availability becomes more important. In order to achieve success, the customer and vendor need to work closely. In previous research the customers’ point of view are mainly presented when examining the offshoring relation, but participation effect the vendor as well. The need to examine the offshoring relationship from the vendor’s point of view has increased as the vendor becomes more significant. This thesis has examined the point of view of Indpro, an IT service provider located in Bangalore (India) primarily serving customers located in Sweden. The empirical materials are based on a field study of Indpro during the author´s ten-week stay in Bangalore, India, where daily work was conducted at Indpro’s office. Materials collected during the field study where analysed through the lens of the theoretical framework created by Balaji & Ahuja (2005), called the offshore project success model. In conclusion, there is no doubt that cross-cultural understanding and clear expectations form the foundation of a trusting relationship between the vendor and the customer, which builds project success.

Les adénocarcinomes rénaux à cellules claires (ccRCC), qui représentent 70% des tumeurs rénales, sont fortement mais irrégulièrement vascularisés, ce qui les rend hypoxiques et donc résistants aux chimiothérapies. L'hypoxie favorise l'agressivité tumorale via l'activation des facteurs de transcription HIF-1alpha et HIF-2alpha (Hypoxia-Inducible Factors). Pour cette raison, le ciblage de l'hypoxie intratumorale et des facteurs HIF dans les ccRCC constitue une stratégie thérapeutique pertinente. Dans ce projet, nous montrons pour la première fois que la voie sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) régule HIF-2alpha in vitro et in vivo. Nos résultats indiquent que la SphK1 régule le taux intracellulaire et l'activité transcriptionnelle de HIF-2alpha dans des lignées de ccRCC représentatives de certains sous-groupes retrouvés en clinique humaine ; et impliquent la S1P extracellulaire, via le récepteur S1P1, dans la régulation de HIF-1alpha et HIF-2alpha. D'autre part, nous avons évalué l'impact de l'inhibition des récepteurs à S1P et de la SphK1 par le FTY720 dans un modèle de ccRCC in vivo. Nos résultats indiquent que le FTY720 entraine une diminution transitoire du taux intratumoral de HIF-1alpha et HIF-2alpha ainsi qu'un remodelage du réseau vasculaire tumoral. En effet, le FTY720 induit une normalisation vasculaire qui aboutit à une oxygénation tumorale transitoire. Enfin, nous montrons que ce traitement permet de sensibiliser un modèle murin de ccRCC à la chimiothérapie. Ces résultats valident le rôle de la voie SphK1/S1P comme régulateur de l'adaptation à l'hypoxie dans les ccRCC. Ils constituent une étape indispensable à la transposition en clinique humaine du concept selon lequel la voie SphK1/S1P peut être ciblée afin de diminuer l'hypoxie intratumorale et de chimiosensibiliser certains cancers, le FTY720 étant déjà sur le marché. / Clear cell renal cell carcinomas (ccRCC) represent 70% of renal tumors. Because of their dense and irregular vascular network, ccRCC become hypoxic and therefore resistant to chemotherapies. Hypoxia promotes tumor aggressiveness via the activation of HIF-1alpha and HIF-2alpha (Hypoxia-Inducible Factors). For this reason, the control of intratumoral hypoxia and HIF in ccRCC could be a relevant therapeutic strategy to improve the efficacy of current treatments. In this study, we show for the first time that the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway regulates HIF-2alpha in vitro and in vivo. Our results indicate that SphK1 regulates HIF-2alpha intracellular level and transcriptional activity in ccRCC cell lines that are representative of some clinical ccRCC subgroups. Our data also involve extracellular S1P, via its receptor S1P1, in the regulation of HIF-1alpha and HIF-2alpha. In addition, in a ccRCC mouse model, we show that FTY720 - an inhibitor of the SphK1/S1P pathway- transiently decreases HIF-1alpha and HIF-2alpha intratumoral level. This is associated with a transient remodeling of the tumor vascular network indicating that FTY720 induces a vascular normalization that leads to transient tumor oxygenation. Finally, we show that this treatment sensitizes a ccRCC mouse model to chemotherapy. Overall, these results validate the key role of the SphK1/S1P pathway in the adaptation to hypoxia in ccRCC cell and animal models. Our results provide a mechanistic basis to target the SphK1/S1P pathway with FTY720 by increasing the efficacy of chemotherapy in ccRCC. They are a prerequisite for clinical transposition as FTY720 is a drug approved used in human clinic.

O carcinoma de célula renal (RCC) subtipo célula clara é o câncer mais letal e prevalente do sistema urinário. O diagnóstico deste tipo de câncer frequentemente é tardio em conseqüência da falta de sintomas perceptíveis aos pacientes. Um dos objetivos deste trabalho é a identificação de novos marcadores moleculares para diagnóstico precoce, o que ajudaria a diminuir a mortalidade em função de complicações resultantes do avanço da doença. Outro objetivo é a identificação de um conjunto de marcadores moleculares de prognóstico, de modo à prever com acurácia a evolução clínica da doença e, por conseqüência, o tempo de sobrevida do paciente. As modificações transcricionais associadas à carcinogênese e à progressão do câncer de rim ainda não foram completamente elucidadas. Além dos oncogenes e genes supressores de tumor, RNAs não-codificadores (ncRNAs) recentemente foram apontados como importantes reguladores da expressão gênica em humanos, e podem ter um papel importante na transformação maligna do câncer de rim. Para analisar a expressão gênica de ncRNAs e de genes codificadores para proteína foram utilizados dois microarranjos desenvolvidos por nosso grupo, enriquecidos em sondas para ncRNAs. Uma das plataformas possui 4 mil sondas de cDNA, das quais 822 sondas são para ncRNAs mapeando em regiões intrônicas. Outra possui 44 mil elementos e combina sondas de oligonucleotídeos (60-mer) intrônicas e exônicas de um mesmo locus genômico. Análises estatísticas foram feitas com a ferramenta Significance Analysis of Microarrays (q &#8804; 0,05) combinadas ou com a técnica de \"patient leave-one-out\" (genes com presença em 8 100% dos subconjuntos), ou alternativamente com o teste discriminante de Golub (p &#8804; 0,01 ou p < 0,05). Com a plataforma de 4 mil sondas foram estudadas 30 amostras de tecido renal de 18 pacientes com RCC subtipo célula clara. Um conjunto de 36 ncRNAs foi identificado como diferencialmente expresso entre amostras tumorais e não-tumorais. Uma assinatura adicional de 265 genes codificadores de proteínas foi identificada, indicando possíveis novos marcadores moleculares. Uma análise estatística supervisionada com dados de 16 pacientes identificou uma assinatura de ncRNAs correlacionada com sobrevida de 5 anos, formada por 27 ncRNAs com significativa expressão alterada em pacientes livres da doença em comparação com pacientes que morreram em função da doença. Uma assinatura adicional de 64 genes codificadores de proteínas também foi identificada como significativamente correlacionada com o acompanhamento clínico dos pacientes. Com a plataforma de 44 mil sondas foram analisados 17 pacientes, com amostras pareadas de tecido renal tumoral e não-tumoral agrupadas em 8 pools, sendo 4 de amostras tumorais e 4 de não-tumorais. Um conjunto de 66 ncRNAs parcialmente intrônicos antisenso e outro de 52 ncRNAs totalmente intrônicos antisenso foram identificados como diferencialmente expressos. Identificamos um subconjunto de 28 ncRNAs totalmente intrônicos antisenso e senso cuja expressão do gene codificador de proteína do mesmo locus estava simultaneamente alterada. Estes dados apontam para possíveis redes de regulação da expressão gênica dos ncRNAs em câncer. A extensa lista de ncRNAs e de genes codificadores para proteína identificados neste estudo podem ser promissores marcadores moleculares de carcinoma renal subtipo célula clara. / Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney, and the clear cell subtype is the most prevalent and lethal cancer of the urinary system. Late diagnosis for this type of cancer is frequent, usually as a consequence of the lack of symptoms. One of the objectives of the present work is the identification of new molecular markers for the early diagnosis, which would help decrease mortality that develops as a function of disease progression. Another objective is the identification of a set of prognosis molecular markers, so as to accurately predict the clinical outcome of the disease, and consequently, patient survival. Transcriptional changes associated to carcinogenesis and to kidney cancer progression have not been entirely elucidated. Besides oncogenes and tumor suppressor genes, non-coding RNAs (ncRNAs) have been recently indicated as important regulators of gene expression in humans, and could have an important role in the malignant transformation in renal cancer. In order to measure ncRNA and protein-coding gene expression we have used two microarray platforms developed by our group, which are enriched in ncRNA probes. One of the platforms has 4 thousand cDNA probes, of which 822 are for ncRNAs that map to intronic regions. Another has 44 thousand elements and combines 60-mer oligonucleotide probes for intronic and exonic regions from the same genomic locus. Statistical analyses have been performed with the Significance Analysis of Microarrays tool (q &#8804; 0.05) combined with a patient leave-one-out approach (genes present in 100% of the sub-sets), or alternatively with Golubs discriminant test (p &#8804; 0.01 or p < 0.05). 11 With the 4-thousand probes platform we studied 30 samples from renal tissue of 18 RCC patients with clear cell subtype. A set of 36 ncRNAs has been identified as differentially expressed between tumor and non-tumor tissue. An additional signature of 265 protein-coding genes has been identified, indicating possible new molecular markers. A supervised statistical analysis with data from 16 patients has identified a ncRNA signature correlated to 5-year survival outcome, comprised of 27 ncRNAs with significantly altered expression in diseasefree patients compared to patients who died from cancer within the 5-year follow-up. An additional 64-gene signature of protein-coding genes has been identified as significantly correlated to clinical outcome. With the 44-thousand probes platform we have analyzed 17 patients, with paired tumor and non-tumor samples grouped into 8 pools, of which 4 were from tumor and 4 from nontumor samples. A set of 66 partially intronic antisense ncRNAs and another of 52 totally intronic antisense ncRNAs have been identified as differentially expressed between tumor and non-tumor tissue. A sub-set of 28 totally intronic antisense or sense ncRNAs were identified as having a simultaneous change in expression of the protein-coding gene from the same locus. Overall, the data point to a possible ncRNA regulatory network in cancer. The extensive lists of ncRNAs and of protein-coding genes identified in the present study can be seen as promising molecular markers of RCC from the clear-cell subtype.

Most Agile Software Development methodologies are aimed towards large companies and large-scale projects. The purpose of this report was to identify, and potentially modify, Agile Development methodologies and strategies suitable for small-scale projects. Initially a comprehensive study was conducted on a few selected agile methodologies in order to find the most suitable one to be used for a loosely defined small-scale project. The result of the study led to the methodology Kanban being used experimentally on that project. The report goes through how Kanban was utilized and modified to better suit the project as well as bring forward interesting details regarding the outcome of the actual project. The produced methodology, with Kanban at its core, can especially be of use for small IT companies looking for an agile methodology fitting their project(s). It could also be used to further develop alternative variants of the agile methodology Kanban with focus on small-scale projects. / De flesta agila utvecklingsmetodiker riktar sig mot storskaliga projekt och företag. Syftet med denna rapport var att identifiera lämpliga agila utvecklingsmetodiker och strategier för småskaliga projekt. Inledningsvis genomfördes en omfattande studie av ett fåtal agila metodiker med målet att hitta den mest lämpliga för ett löst definierat småskaligt projekt. Resultat av studien ledde till att metodiken Kanban experimenterades med och användes för projektet. Rapporten går igenom hur Kanban nyttjades och modifierades för att bättre passa projektet i fråga. Den framtagna metodiken, med Kanban som grund, kan vara speciellt användbar för mindre IT-företag som letar efter en agil metodik som passar deras projekt. Den skulle även kunna användas för att vidareutveckla alternativa agila Kanban-metodiker för småskaliga projekt.

The population dynamics and demography of Daphnia galeata was analysed in a five year study in the biomanipulated Bautzen Reservoir. Samples were taken two times a week during the period May-July in the pelagic zone of this highly eutrophic water. Major bottom-up and top-down factors were determined during the study period and analysed with regard to their influence on Daphnia dynamics and life history. Field data on fecundity and population structure of D. galeata were combined with results from life table and growth experiments performed under approximately in situ conditions to gain insight into the mechanisms leading to a midsummer decline of this cladoceran species which dominates the zooplankton community in Bautzen Reservoir. Two main patterns of Daphnia dynamics emerged: In years without a midsummer decline the population increased slowly in spring, starting from low densities. High water transparency was observed already during the build-up of the population of D. galeata. Despite considerable fluctuations, Daphnia abundance remained on a high level throughout summer. In years with a midsummer decline the population started from relatively high densities in early May and more than doubled during one week. Peak densities were reached before the clear-water stage emerged. At the end of this period the population declined to low values which lasted for the rest of the summer. Fecundity of the Population of D. galeata declined, whereas the mean egg volume increased at the beginning of the clear-water stage as a result of declining food levels. The size at maturity (SAM) remained high during this period. Additionally, juvenile growth was reduced and the age at maturity was retarded. Survival probability was low for those daphnids born shortly before or during the clear-water stage compared to those born later. It can be concluded from these results that recruitment to adult stages is strongly reduced during the clear-water stage. The end of this period is marked by an alternation in generations. Only at that time can SAM be reduced because the new generation of adults matures at a smaller size, carrying small eggs. A high impact of non-predatory adult mortality can be expected when the population is dominated by a strong peak-cohort during the clear-water stage according to recruitment patterns during the build-up of the population. The most drastic decline both of Daphnia abundance and SAM was observed in those years when the biomass of juvenile fish exceeded 20 kg ha-1 at the end of the clear-water stage. Due to gape-size limitation juvenile fish mainly feed on juvenile daphnids during this period and thus, they reinforce bottom-up effects on the Daphnia population. When fish change their size selection towards adult daphnids at the time when the new generation takes over, this seems to represent the worst case for the Daphnia population. Consequently, the timing between bottom-up effects and the feeding pressure of juvenile fish determines the extent of the decline. - (This manuscript is also available - in the form of a book - from Shaker Verlag GmbH, Postfach 101818, 52018 Aachen, Germany world-wide web address: http://www.shaker.de, electronic-mail address: info@shaker.de. It has been posted on the web sites of Dresden University of Technology with the permission of the publisher)

Systematic reviews on diagnostic test accuracy studies provide an overview of the current literature in a systematic and transparent manner. They are the highest level of evidence in clinical research, therefore they are critical to decision-making in the healthcare setting. Cancer is the primary source of mortality in Canada, however early detection of tumors can improve the survival rates and long-term health outcomes of patients. The primary method of cancer diagnosis is histopathological assessment, however, its use remains controversial. It is an invasive procedure and requires resources and clinical expertise not readily available. Noninvasive clinical imaging has been studied as a clinically desirable method for cancer diagnosis, however its diagnostic accuracy has yet to be established in the medical setting. With the increased role of DTA research in medicine, the current literature needs to be summarized in an effective way to properly educate and influence clinical decision-making. The objective of this thesis is to address the current evidence gaps in DTA research by conducting several systematic reviews to evaluate the accuracy of diagnostic methods in cancer-related imaging. The last chapter of the thesis will provide a critical reflection on the current landscape of DTA studies in cancer-related imaging, based on the findings of the reviews in the thesis.