Les carcinomes rénaux représentent environ 3% des cancers chez l’adulte. Les plus fréquents parmi ces tumeurs sont les carcinomes rénaux à cellules claires (CRCC) (70% des cas). Dans une première partie, nous avons analysé le caryotype de 89 patients ayant subi une néphrectomie pour CRCC et avons corrélé les déséquilibres chromosomiques avec les principaux facteurs histo-pronostiques et cliniques de ces tumeurs. Cette étude nous a permis de confirmer l’impact diagnostique et/ou pronostique d’anomalies chromosomiques. Certaines étaient déja connues dans la littérature comme la perte du bras court d’un chromosome 3 à impact diagnostique ou la perte d’un chromosome 9 ou de son bras court associée à un pronostic défavorable. Nous avons ensuite, dans une seconde partie, sélectionné selon des critères cliniques et histologiques, deux lignées cellulaires R-180 et R-305 établies à partir de prélèvements chirurgicaux de CRCC de patients dont l’évolution clinique était défavorable pour le patient R-180 (survie de 1 an) et favorable pour le patient R-305 (survie de 7 ans). Nous avons analysé les profils cytogénétiques des deux lignées cellulaires et recherché des marqueurs d’intérêt. Nous avons mis en évidence une amplification du gène pard3 dans la lignée R-180 correspondant au patient qui est décédé 1 an après le diagnostic. Cette amplification a été associée à la surexpression de la protéine correspondante PAR-3 et à des modifications de l’organisation du cytosquelette. La diminution de l’expression de PAR-3 par transfection de siRNA dans les cellules R-180 a permis la restauration de l’organisation du cytosquelette et la réduction des capacités de migration cellulaire par rapport aux cellules non transfectées. Ce résultat suggère un rôle de PAR-3 dans la migration cellulaire des cellules R-180. Afin de valider la pertinence de ce nouveau biomarqueur dans le CRCC, nous avons étudié 101 tumeurs par immunohistochimie. Nous avons montré une corrélation significative entre la surexpression de PAR-3 dans la tumeur primitive des patients et une diminution de la survie globale et de la survie sans progression indépendamment d’autres facteurs pronostiques importants comme les métastases. De plus la surexpression de PAR-3 a été significativement associée aux facteurs histopathologiques et cliniques de mauvais pronostic : grades nucléaires de Fuhrman III ou IV, nécrose tumorale, composante sarcomatoide, atteinte surrénale, invasion de la graisse rénale ou hilaire, composante éosinophile, statut non-inactivé du gène VHL, grade tumoral plus élevé, envahissement ganglionnaire ou métastatique, et score ECOG (Eastern Cooperative Oncology Group) péjoratif. L’ensemble de nos résultats suggèrent que la surexpression de PAR-3 est associée à un risque significatif de progression et de mortalité dans le CRCC. Sa mise en évidence par immunohistochimie en routine hospitalière pourrait être utile pour identifier les patients à haut risque de progression, même en l’absence des paramètres pronostiques habituels. Des études complémentaires sont en cours pour intégrer ce biomarqueur dans les nomogrammes ainsi que pour évaluer l’impact de cette dérégulation dans la résistance des CRCC aux thérapies ciblées. / Kidney cancers represent about 3% of all adults’ malignancies. The most common form of kidney cancer is renal carcinoma of which 70 % of cases are defined as clear cell Renal Cell Carcinoma (ccRCC). We undertook a systematic review of all ccRCCs with a total of 89 patients who underwent nephrectomy surgery. We assessed the karyotype profile of all patients that we correlate with an immunohistochemical features and tumor symptoms. This study demonstrates a high impact of chromosomal abnormalities on patients’ diagnosis and prognosis. Some of these abnormalities have been submitted in other publications as the loss of the chromosome 3 p-arm which has a diagnosis impact, and the loss of the chromosome 9 or it s p-arm that have a poor prognosis impact. We selected two cell lines (R-180 and R-305) derived from ccRCC surgical specimens of a patient with unfavorable clinical course (R-180 cells) and a patient with favorable prognosis (R-305 cells) to identify genetic and molecular features that may explain the survival difference of the two patients. The cytogenetic analysis of these cell lines revealed that the pard3 gene was amplified only in the R-180 cell line that was derived from an aggressive ccRCC. The pard3 gene amplification was associated with overexpression of the encoded protein and altered cytoskeleton organization. PAR-3 knockdown in R-180 cell restored the cytoskeleton organisation and reduced cell migration in comparison to non-transfected cells. These results suggest PAR-3 role in R-180 migration cells line. With a view to corroborate the relevance of this new biomarker PAR-3 in ccRCC, we have studied 101 tumors using immunohistochemical methods. We proved a significant correlation between PAR-3 overexpression in the primitive tumor and, the decreasing of overall and free progression survival independently of other risk factors as metastasis. We also fund that the overexpression of PAR-3 is associated with an unfavorable clinical and immunohistochemical prognosis factors such as: stage III -IV in fuhrman system grading ,tumor necrosis, sarcomatoide component, supra renal metastasis, cancer spreading (surrounding fat and hilar), eosinophil component , none inactivate VHL gene, high tumor stage, lymph nodes spread, metastasis and ECOG scale. Our results reveal that the PAR-3 overexpression is associated with significant risk of ccRCCs mortality and spreading tumor. Immunohistochemical screening may be usefulness to identify patient’s high spreading risk whether the lack of the habitual prognosis parameters. Other studies are in progress to integrate this biomarker in nomograms and also to evaluate the impact on ccRCC’s resistance to targeted therapy.

Quarante ans après la découverte de la circulation hydrothermale profonde, les processus chimiques se produisant dans le mélange entre le fluide hydrothermal et l’eau de mer restent mal contraints. Ce travail de thèse, dont l’originalité repose sur l’utilisation systématique de la filtration in situ, présente le partitionnement effectif des éléments métalliques majeurs (principalement Fe, Cu, Zn, Ba et Ca) entre les phases dissoutes (< 0,45 μm) et particulaire (> 0,45 μm) dans le mélange précoce-intermédiaire de plusieurs fumeurs du champ hydrothermal Lucky Strike (37°N, MAR). Le comportement et la spéciation du Cu dans la fraction dissoute sont ensuite explorés plus en détail par le biais de compétitions de ligands et de mesures voltamétriques. Nos résultats démontrent en premier lieu l’importance de la filtration in situ pour s’affranchir des biais induits par le prolongement des réactions de précipitation ou de redissolution pouvant se produire lors de la remontée des échantillons. L’examen des fluides collectés à différentes reprises et sur une large panoplie de fumeurs (240 échantillons) démontre une variabilité spatiale des signatures chimiques le long de l'axe est-ouest du champ hydrothermal. Parmi les métaux étudiés, Fe, Ca et Ba sont principalement mesurés sous forme dissoute tandis que Cu et Zn sont majoritairement particulaires. Dans le mélange initital (50‒150°C, dMn > 50 μM), le pool de particules est dominé par de la sphalérite (ou wurtzite) et de la chalcopyrite, avec généralement moins de pyrite. Dans cette zone, les changements chimiques semblent cinétiquement limités et les fluides échantillonnés présentent une signature chimique proche de celle du fluide pur. Cependant, à mesure que le fluide hydrothermal se mélange à l'eau de mer (4‒50°C, dMn < 50 μm), le partitionnement de certains métaux alcalins et alcalinoterreux (Ca, Ba, Mg et Sr) entre les deux phases est profondément affecté par la précipitation de sulfates. Contrairement aux prédictions thermodynamiques, la précipitation d’anhydrite, de barite et potentiellement de caminite est observée dans la partie relativement froide du mélange (4-50°C). L’augmentation importante du pH dans cette zone conduit également à l’initiation de la précipitation d’oxydes de Fe. Enfin, dans la phase dissoute, les ligands du Cu semblent être principalement des sulfures inorganiques issus du fluide hydrothermal. / Forty years after the discovery of deep hydrothermal circulation, chemical processes occurring in the early mixing between hydrothermal vent fluids and deep seawater are still not fully constrained. This thesis, whose the originality lies on the systematic use of in situ filtration, report on the partitioning of major metals (mainly Fe, Cu, Zn, Ba and Ca) between the dissolved (< 0.45 μm) and particulate (> 0.45 μm) phases in the early mixing of several black and clear smokers from the Lucky Strike vent field (37°N, MAR). The behavior and the speciation of Cu in the dissolved fraction are then deeper explored by performing ligands competition and voltammetric measurements. Our results first demonstrate the importance of the in situ filtration to restrict the bias induced by precipitation reactions or particles redissolution potentially occurring postsampling.The examination of the fluids collected at several occasions and on a wide range of smokers (240 samples) shows a spatial variability of chemical signatures along the east-west axis of the hydrothermal field. Among metals studied, most of Fe, Ca and Ba are measured as dissolved species whereas Cu and Zn are mainly found as particles. In the initial part of the mixing (50-150°C, dMn > 50 μM), the particulate pool is dominated by sphalerite (or wurtzite) and chalcopyrite, with generally lower amount of pyrite. In this zone, chemical changes seem kinetically limited and fluids collected display a chemical signature close to that of the end-members. However, as the hydrothermal fluid progressively mixes with seawater (4-50°C, dMn < 50 μm), the partitioning of some alkali and alkaline earth metals (Ca, Ba, Mg and Sr) between the two phases is deeply affected by precipitation of sulfates. Unlike thermodynamic predictions, precipitation of anhydrite, barite and potentially caminite is observed in the colder part of the mixing (4-50°C). The large increase of pH in this area also drives the beginning of Fe oxides precipitation. Finally, the dissolved Cu-ligands detected seem to be mainly inorganic sulfides originating from the hydrothermal fluid.

The trophic state of lakes is commonly defined by the concentration of nutrients in the water column. High nutrient concentrations generate high phytoplankton production, and lakes with low nutrient concentrations are considered low-productive. This simplified view of lake productivity ignores the fact that benthic primary producers and heterotrophic bacteria can be important basal producers in lake ecosystems. In this thesis I have studied clear-water and brown-water lakes with respect to primary production, respiration and bacterial production based on allochthonous organic carbon. These processes were quantified in pelagic and benthic habitats on temporal and spatial scales. I also calculated the net ecosystem production of the lakes, defined as the difference between gross primary production (GPP) and respiration (R). The net ecosystem production indicates whether a lake is net heterotrophic (GPP &lt; R), net autotrophic (GPP &gt; R) or in metabolic balance (GPP = R). Net heterotrophic lakes are sources of carbon dioxide (CO2) to the atmosphere since respiration in these lakes, by definition, is subsidized by an external organic carbon source. External organic carbon is transported to lakes from the terrestrial environment via inlets, and can serve as a carbon source for bacteria but it also limits light availability for primary producers by absorbing light. On a seasonal scale, four of the clear-water lakes studied in this thesis were dominated by primary production in the soft-bottom benthic habitat and by respiration in the pelagic habitat. Concentrations of dissolved organic carbon (DOC) were low in the lakes, but still high enough to cause the lakes to be net heterotrophic. However, the lakes were not low-productive due to the high production in the benthic habitat. One of the clear-water lakes was studied also during the winter and much of the respiration under ice was supported by the benthic primary production from the previous summer. This is in contrast to brown-water lakes where winter respiration is suggested to be supported by allochthonous organic carbon. By studying lakes in a DOC gradient (i.e. from clear-water to brown-water lakes) I could draw two major conclusions. The lakes became less productive since benthic primary production decreased with increasing light extinction, and the lakes became larger sources of CO2 to the atmosphere since pelagic respiration was subsidized by allochthonous organic carbon. Thus, lake carbon metabolism can have an important role in the global carbon cycle due to their processing of terrestrial organic carbon and to their possible feedback effects on the climate system.

This document focuses on the formal structures and tonal language of four trios that include horn by American composer Simon A. Sargon: "Huntsman, What Quarry?" Two Poems of Edna St. Vincent Millay for Soprano, Horn, and Piano (1990); Trio for Horn, Violin, and Piano: "The Legacy" (1993); A Clear Midnight: Six Songs Set to Poems of Walt Whitman for Baritone, Horn, and Piano (1996); and Sonic Portals: Trio for Oboe, Horn, and Piano (2003). Comparisons with precedent works of like instrumentation demonstrate that Sargon's trios, though musically unique, merit a place alongside masterworks like Carl Reinecke's Trio, op. 188, for oboe, horn, and piano; Franz Schubert's Auf dem Strom for soprano, horn, and piano; and especially Johannes Brahms's Trio, op. 40, for violin, horn, and piano. Other precedent, contemporary, and related works are also mentioned. Sargon's ability to write idiomatically for the horn and other instruments is discussed, and consideration is given to some elements required to create a good performance of Sargon's chamber music. Included are a brief biography of Simon Sargon, letters from colleagues with whom he has worked closely, lists of his instrumental music and recordings of some of these pieces, and lists of other works in the genres discussed herein.

The thesis focuses on the solution of the bridge construction made of prestressed concrete. The bridge is situated on the road II/485 and it is headed over the road I/48. Cathegory of the road communication is S 7,5. The construction is continuous and consists of five arrays. The lenght of the bridge construction is 125,1 m. The burden to the construction is according to ČSN EN 1991-2 standard. Inner forces are solved by using computational model. This model works on the FEM calculation axiom. The size is according to ČSN EN 1992-1-1 and ČSN EN 1992-2 standards.

What lies beneath the surface of modern day interfaces? And what are the consequences of sharing our digital self with companies in exchange for free services? We report on a study of smartphone users in Sweden where behaviours and reactions are assessed from a critical viewpoint using the suggested method “Clear the palace”. Users express concerns regarding management of the digital self as well as showing awareness of the limitations within personalization as a result of data mining. Strategies to limit mobile overuse are discussed. The analysis is based on; Shklovski’s notions privacy paradox and creepiness and Pierce’s framework of undesigning technology. Clear the Palace as a methodology is assessed aswell as societal implications of data mining are problematized. / Vad pågår under ytan av moderna gränssnitt? Och vad är konsekvenserna av att vi delar våra digitala jag med företag i utbyte mot gratis tjänster? Vi redogör för en studie av mobilanvändare i Sverige där beteenden och reaktioner studeras ur ett kritiskt perspektiv med metoden “Röj palatset”. Användare uttrycker oro gällande hanteringen av det digitala jaget och uppvisar medvetenhet angående begränsningarna av personalisering som en följd av data mining. Strategier för att begränsa överanvändning av smartmobiler diskuteras. Analysen baseras på; Privacy Paradox, Leakiness/Creepiness enligt Shklovski och Pierce ramverk Undesigning Technology. Röj palatset som metod utvärderas och implikationer av data mining för samhället problematiseras.

The aim of this thesis was to investigate the processes behind an unexpected runoff behaviour after a clear-cut in a boreal forest in northern Sweden (Balsjö). The risks of increased flooding, erosion, nutrient leakage and changes in the local ecosystems are some reasons why it is important to fully understand the effect of clear-cuts on the water balance. In northern boreal forests the snow is of great importance as it results in the main hydrological event of the year, the spring flood. In general, open areas accumulate more snow, have a lower evapotranspiration and therefore maintain a higher runoff than a forest. In a recent paired catchment study at Balsjö the expected pattern after a clear-cut was only shown in three out of five years (2007-2011). The expected increase in runoff did not occur in 2010 and 2011. Two hypothesized alternatives were year-to-year variation of ET or changes in soil water storage. In order to investigate this further the rainfall-runoff model HBV was used. First, the model was calibrated for the forest catchment (Ref) and the clear-cut catchment (CC), using observed data from Balsjö. To account for parameter uncertainty the calibration was performed using parameter optimization, resulting in 100 different parameter sets. Model results were evaluated using observed snow data from Balsjö and ET from Flakaliden, a nearby forest. Both the simulated snow and ET were quite consistent with the observed values. Finally the annual and the spring water balance were studied, using the simulated data. The simulated results did not detect the unexpected runoff behavior for the two years as clearly as the observations. The reason for this was that the model was calibrated for all five years, which meant that annual variations were not taken into account. The hypothesis, that higher ET could be the reason for the unexpected runoff behavior, could neither be dismissed nor confirmed by this thesis. This was because there were no observed data for the clear-cut area and limitations within the HBV model, which meant that sublimation and interception processes could not be analyzed separately. The model results indicated that the change in soil water storage was a more likely explanation for the unexpected runoff behavior. The simulation result showed that the meltwater was stored in the soil water storage. However, this theory does not seem likely since a clear-cut is normally wetter than a forest. The results of this thesis are consistent with other studies as they indicate that clear-cut effects should be studied seasonally as well as annually. The special feature of this thesis was the opportunity to study observed ET and investigate its influence on the water balance.

Indiana University-Purdue University Indianapolis (IUPUI) / Automotive paints have used an ultraviolet (UV) absorbing clear coat system for nearly thirty years. These clear coats have become of forensic interest when comparing paint transfers and paint samples from suspect vehicles. Clear coat samples and their ultraviolet absorbers are not typically examined or characterized using Raman spectroscopy or microspectrophotometry (MSP), however some past research has been done using MSP. Chemometric methods are also not typically used for this characterization. In this study, Raman and MSP spectra were collected from the clear coats of 245 American and Australian automobiles. Chemometric analysis was subsequently performed on the measurements. Sample preparation was simple and involved peeling the clear coat layer and placing the peel on a foil-covered microscope slide for Raman or a quartz slide with no cover slip for MSP. Agglomerative hierarchical clustering suggested three classes of spectra, and principal component analysis confirmed this. Factor loadings for the Raman data illustrated that much of the variance between spectra came from specific regions (400 – 465 cm-1, 600 – 660 cm-1, 820 – 885 cm-1, 950 – 1050 cm-1, 1740 – 1780 cm-1, and 1865 – 1900 cm-1). For MSP, the regions of highest variance were between 230 – 270 nm and 290 – 370 nm. Discriminant analysis showed that the three classes were well-differentiated with a cross-validation accuracy of 92.92% for Raman and 91.98% for MSP. Analysis of variance attributed differentiability of the classes to the regions between 400 – 430 cm-1, 615 – 640 cm-1, 825 – 880 cm-1, 1760 – 1780 cm-1, and 1860 – 1900 cm-1 for Raman spectroscopy. For MSP, these regions were between 240 – 285 nm and 300 – 370 nm. External validation results were poor due to excessively noisy spectra, with a prediction accuracy of 51.72% for Raman and 50.00% for MSP. No correlation was found between the make, model, and year of the vehicles using either method of analysis.

Background Globally, the COVID-19 pandemic presented major difficulties for many self-employed people because it caused pressures such as decreased customer demand, production stagnation, disruptions in supply chains and increased uncertainty. The vast amount of the studies of self-employed people during the pandemic have focused on traditional pathogenic effects. Hence, overall aim of this thesis is to explore how self-employed people experienced and used internal and external salutogenic resources to navigate the pandemic, from a business challenge and an individual well-being perspective.  Methods Different methods of data collection and analysis were employed in the thesis. For study I, a qualitative design was used to explore whether a sense of coherence was experienced, and any general resistance resources were used by small business managers in Sweden and Norway during the pandemic. For study II, a cross-sectional quantitative design was employed to investigate the well-being of self-employed people in Europe during the pandemic and whether their well-being was influenced by factors representing four socio-ecological levels. Lastly, study III applied a mixed-method design including comparative policy analysis and interviews to gain an understanding of how different governmental financial support measures aimed to aid the resilience of Swedish and Canadian self-employed people and improve their ability to manage the COVID-19 pandemic. Study I was analysed through a deductive content analysis, study II was analysed using independent sample t-tests, correlations and linear regression, and study III used comparative policy analysis and inductive content analysis.  Results Findings from the interviews in study I demonstrated that it was important for the participants to comprehend and manage challenges during the pandemic in a resourceful manner, and to see meaningfulness in their situations. In study II, the findings highlight that the socio-ecological factors of resilience, social support, doing useful work and experiencing rules as clear affected the self-employed people’s well-being, and that these factors may be even more important for those who had difficulties running their business. Study III found that self-employed people in both Sweden and Canada who 10 were unable to telework were relatively less resilient during the pandemic. The interviews revealed that many self-employed people in hard-hit industries were dissatisfied with government financial support measures and found them to be unfairly distributed. In addition, the self-employed people who experienced difficulties running their businesses reported reduced well-being, which had a negative effect on their business survival.  Conclusion  While the three studies in this thesis had different foci, they collectively provide insights into the internal and external salutogenic resources that influenced how self-employed people navigated the pandemic. A sense of coherence, resilience and well-being were deemed important for handling the pandemic well, for both the individuals and their businesses. The research also indicated the interconnectedness between self-employed people and their businesses. For instance, financial difficulties may lead to increased stress and pressure to make decisions to sustain the business. Reduced well-being, in turn, made it harder to adapt and adjust positively to adversity. The importance of supporting factors at multiple socio-ecological levels was also highlighted, and these may be particularly important to those who had difficulties running their businesses.

No description available.