Les effets du changement climatique ont d’ores et déjà été observés sur la vigne : avancement des stades de développement, augmentation des teneurs en alcool des vins, baisse excessive de leur acidité. Une des voies d’adaptation possible de la viticulture est la création de nouvelles variétés. J’ai caractérisé la variabilité phénotypique de 120 descendants de croisements entre Riesling (RI) et Gewurztraminer (GW) pour (1) les stades de développement, décrits à l’aide de sommes de températures (2) la capacité à accumuler des sucres dans les raisins (3) les paramètres de l’acidité des raisins. L’utilisation de marqueurs moléculaires sur l’ADN a permis de mettre en évidence des relations entre données génétiques et phénotypiques pour tous les caractères étudiés (QTLs ou Quantitative trait loci). La principale conclusion est que la variabilité génétique pour les paramètres de l’acidité des raisins est la voie à valoriser en priorité pour l’adaptation de la vigne au changement climatique. / The effects of climate change have already been observed on the grapevine : advance of phenological stages, increase in the alcohol content of the wines, excessive decrease of their acidity. Breeding new varieties is one of the possible means of adaptation. I have characterized the phenotypic variability of 120 genotypes, offspring from crossings between Riesling (RI) and Gewurztraminer (GW)for (1) the developmental stages, described with heat sums (2) the ability to accumulate sugars in the berries (3) the parameters for acidity. The use of DNA molecular markers allowed the detection of quantitative trait loci (QTLs) for all the traits studied. The main conclusion is that the genetic variability for the parameters determining the acidity of the berries is the most promising for the adaptation of grapevine cultivation to climate change.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Calcination variables, temperature, time and heating rate, used in obtaining different transition aluminas were simultaneously investigated using statistical experimental design. Empirical models correlating catalyst final properties and calcination conditions were employed. It was found that all calcination variables play fundamental roles on acidity of alumina catalyst. Furthermore, interaction effects among these variables and non-linear effects also are of fundamental importance for the final properties catalyst. Therefore, the use of simultaneous variation of calcination conditions through experimental design is of great importance in detecting such interactions. It was observed that the use of high heating rates favor the formation of pore with larger diameters and with high pore volume and, for short calcination time, high heating rate also contributes to the formation of higher concentration of acid sites. The acid sites characterization of transition aluminas were performed by temperature programmed desorption of ammonia (NH3-DTP), which showed that there are two distinct acid sites on the surface these materials. The desorption dates were adjusted by a model in which the catalyst bed was considered as single continuously stirred tank reactor and the intrinsic kinetic was chosen to be of first order for adsorption and desorption. The ethanol conversion was higher for the alumina with higher acid sites concentration, suggesting a relationship between the activity of the alumina for the ethanol conversion and its acidity. The selectivity for the ethylene formation also was higher for the more acid aluminas, while the selectivity to ether presented opposite behavior. Therefore, a successful control of all calcination conditions can be an effective method to adjust the final physical and chemical properties of transition alumina catalyst, aiming the highest yield of ethylene from ethanol dehydration. / Foram preparadas aluminas de transição investigando-se simultaneamente o efeito das variáveis de calcinação: temperatura, tempo e taxa de aquecimento, usando planejamento estatístico de experimentos. Modelos empíricos foram empregados para correlacionar as propriedades finais dos catalisadores às variáveis de calcinação. Foi observado que todas as variáveis de calcinação influenciam a concentração de sítios ácidos das aluminas. Além disso, efeitos de interação entre estas variáveis, bem como efeitos não lineares também são de fundamental importância para as propriedades finais deste catalisador. Estes efeitos só podem ser identificados com a variação simultânea das condições de calcinação através do uso do planejamento de experimentos. Foi observado que o uso de elevada taxa de aquecimento favorece a formação de aluminas com maior volume e tamanho de poros e, para curtos períodos de tempo de calcinação, elevada taxa de aquecimento também contribui para a formação de maior concentração de sítios ácidos. A caracterização dos sítios ácidos das aluminas foi realizada pela técnica de dessorção de amônia à temperatura programada (DTPNH3). Esta caracterização indicou a presença de dois tipos de sítios ácidos na superfície destes materiais. Os dados de dessorção foram ajustados por um modelo que considera a cinética de dessorção e readsorção como reações de primeira ordem em um modelo de reator de mistura perfeita. A conversão de etanol foi maior para as aluminas com maior concentração de sítios ácidos, indicando uma relação entre a atividade das aluminas para a conversão de etanol e sua acidez. A seletividade para a formação de eteno também foi maior para as aluminas mais ácidas, enquanto que a seletividade para éter exibiu comportamento inverso. Portanto, o controle adequado de todas as condições de calcinação pode ser um método eficiente para ajustar as propriedades físicas e químicas finais de aluminas de transição, visando obter maior rendimento na produção de eteno a partir da desidratação de etanol.

Submitted by Biblioteca de Pós-Graduação em Geoquímica BGQ (bgq@ndc.uff.br) on 2017-12-18T14:58:25Z No. of bitstreams: 1 Dissertação realmente corrigida.pdf: 2600370 bytes, checksum: f6dfd5312d899b3cc7513282683ff5be (MD5) / Made available in DSpace on 2017-12-18T14:58:25Z (GMT). No. of bitstreams: 1 Dissertação realmente corrigida.pdf: 2600370 bytes, checksum: f6dfd5312d899b3cc7513282683ff5be (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Universidade Federal Fluminense. Instituto de Química. Programa de Pós-Graduação em Geoquímica, Niterói, RJ / Pode-se considerar a química das águas naturais dividida em duas categorias de reações mais comuns: as reações ácido-base e as de oxidação-redução. Os fenômenos ácidobase e de solubilidade controlam o pH e as concentrações de íons inorgânicos, resultando em composição química variada de acordo com as condições bioclimáticas. A origem da acidez de uma água natural pode estar relacionada à geoquímica e ao aporte de matéria orgânica e nutrientes, fenômeno frequente em ambientes que apresentam drenagem sob turfeira. As turfeiras são ambientes especiais para estudos relacionados com a dinâmica da matéria orgânica, elas contribuem para o sequestro global de carbono, além de funcionarem como reservatórios de água. Nesse contexto, o objetivo desse trabalho foi analisar a correlação da matéria orgânica e da interação água-rocha com a acidez observada na nascente do rio Campo Belo, situada à 2419 m de altitude, no Maciço do Itatiaia. Para isso, foram coletadas amostras de água e solo, submetidas à analise dos parâmetros físico-químicos in situ e análise dos íons maiores e elementos traço em laboratório. Os resultados encontrados foram utilizados para a realização da modelagem para especiação de íons em água e tratamento estatístico multivariado, que mostraram que a disponibilidade do alumínio no solo está correlacionada com as variações do pH ao longo do perfil. A liberação do alumínio aumenta a acidez do sistema através da hidrólise ácida da água, o que por sua vez, favorece o aumento da desmineralização e lixiviação de bases, favorecendo a concentração e retenção do alumínio no solo. Embora a matéria orgânica não seja responsável pela acidez, a presença da turfa é fator imprescindível para a manutenção da acidez, pois atua como sequestrador de bases ao formar complexos com as substâncias húmicas, além de exercer papel tamponante no sistema. / The chemistry of natural waters can be divided in two more common reaction categories: acid-base reactions, and oxidation-reduction reactions. Acid-base and solubility phenomena control the pH and the inorganic ions concentrations, which result in diverse chemical composition, according to bioclimatic conditions. Acidity origin of natural waters can be related to its geochemistry and to organic matter and nutrient supplies, which are frequent phenomena in environments that present drainage underneath turf. Turfs are special environments for studies related to organic matter dynamic, they contribute to carbon global sequestration, besides functioning as water reservoirs. In that context, the aim of this work was to analyse the correlation between organic matter and water-rock interaction with the acidity observed at the Campo Belo river spring, located at 2419 m of altitude, at the Itatiaia massif. For that, water and soil samples were collected, and analised in terms of their physical-chemical parameters, in situ, and also analysis of the major ions and trace elements in laboratory. The observed results were used in an ion speciation modeling in water, and multivariate statistical analysis, that showed that the availability of aluminum in the soil is correlated to the pH variations along the soil profile. The liberation of aluminum increases the system acidity through acidic hydrolysis of water, which, in turn, promotes the increase of the demineralization and leaching of basis, favoring the concentration and retention of the aluminum of the soil. Despite the organic matter is not responsible for the acidity, the presence of turf is an indispensable factor for the maintenance of the acidity, since it acts as basis sequestrant as it forms complexes with humic substances, besides playing a role in buffering the system.

Made available in DSpace on 2014-07-29T14:42:44Z (GMT). No. of bitstreams: 1 Weslwy alves martins.pdf: 1658428 bytes, checksum: 034cb01372fc23e0a439a66aedfd973a (MD5) Previous issue date: 2007-07-24 / The experiment was carried out in Santa Rita do Araguaia Goiás, in a commercial orchard settled in the Sperafico Site, with total area of 1,7 ha, placed on BR-364 Rd, Km 372, from Goiânia to Cuiabá. This trial with the grapevine Niagara Rosada was done from October 2007 to October 2008. The aim of the research was to study the characteristics of the cultivar Niagara Rosada (Vitis labrusca L.) undergone ten pruning times in Santa Rita do Araguaia GO. The cycle duration (pruning harvest) varied from 121 to 141 days for the 10 pruning times. The pruning times presented differences in the sum of degree-days needed to complete the cycle in the same site. The pruning times did not affect the form of the bunches significantly. Nevertheless, they affected the size of the bunches significantly, especially pruning time P9 (5/10/2008) with 11,60cm and P10 (5/24/2008). The largest berry diameter was found in the pruning times P1 (10/24/2007) and P2 (11/09/2007), with 18,60mm and 18,0mm respectively, patterns considered appropriate for cultivation of Niagara Rosada . The different pruning times showed influence on soluble solids levels, with the highest average of 18.4 ºBrix for pruning time P8 (4/26/2008). However, there was significant variation for the acidity titratable, and for the Ph, the highest value was 4.0, in pruning times P8, P9 and P10. The highest yield was obtained in pruning times P7 (3/28/2008) with 12,63 t ha and P10 (5/24/2008) with 12,12 t ha. Taking into account the thermal requirements and the cycle of the grapevine Niagara Rosada in Santa Rita do Araguaia, it is possible to estimate the date for each of the phenological sub- periods, as well as to predict harvest time. / O experimento foi desenvolvido no município de Santa Rita do Araguaia Goiás, em pomar comercial instalado no Sítio Sperafico, com área total de 1,7 ha, localizado na rodovia BR-364, km 372 no sentido Goiânia-Cuiabá. A condução do experimento com a videira Niagara Rosada foi durante o período de outubro de 2007 a outubro de 2008. O presente trabalho teve por objetivo estudar as características da cultura da uva Niagara Rosada (Vitis labrusca L.) submetida a dez épocas de poda no município de Santa Rita do Araguaia GO. A duração do ciclo produtivo (poda colheita) variou de 121 a 141 dias para as 10 épocas poda. As épocas de poda apresentaram diferenças no somatório de graus-dia necessários para completar o ciclo no mesmo local. As épocas de podas não afetaram significativamente a forma dos cachos, entretanto, afetaram significativamente o tamanho dos cachos, com maior destaque para as épocas E9 (10/05/08) com 11,60cm e E10 (24/05/08). O maior diâmetro de baga foi encontrado nas podas E1 (24/10/07) e E2 (09/11/07) com médias de 18,60mm e 18,0mm respectivamente, médias consideradas adequadas para a Niagara Rosada. As diferentes épocas de poda exerceram influência sobre os teores de sólidos solúveis, com uma maior média de 17,40 ºBrix para época E8 (26/04/08). Todavia, houve variação significativa acidez titulável, e para o pH, o valor mais elevado foi 4,0, nas podas E8, E9 e E10. A maior produtividade foi verificada para as épocas E7 (28/03/08) com 12,63 t/ha e E10 (24/05/08) com 12,12 t/ha. Conhecendo-se a exigência térmica e o ciclo da videira Niagara Rosada em Santa Rita do Araguaia, é possível estimar a data em que ocorrerá cada um dos subperíodos fenológicos e prever a época de colheita.

Made available in DSpace on 2015-04-20T12:31:32Z (GMT). No. of bitstreams: 1 Aloisio Freitas Chagas Junior.pdf: 1425510 bytes, checksum: 861fcee7c2ea43864c650307852db610 (MD5) Previous issue date: 2007-04-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / To increase the rhizobia contribution to plants nutrition and development is necessary to develop researches for selecting more efficient nitrogen fixation strains. This research work had as objectives, to accomplish morphologic characterization of rhizobia isolated from Amazonian soils; laboratory evaluations about the tolerance to acidity and toxic Al, the capacity to solubilize calcium (P-Ca) and aluminum (P-Al) phosphates, the indole-acetic acid production (AIA); the ability of the isolates to induce nodulation and to fix nitrogen under the acidity and low fertility conditions of the regional soils in greenhouse experiment; to genetically characterize the isolated ones selected using the PCR-RFLP technique. The infectivity test showed that there was significant increase in the cowpea biomass. With relationship to the phenotypic characterization, the 200 isolates showed a great diversity. Among these, 165 and 127 presented high tolerance within the media with pH 4,5 and pH 4,5 + Al, respectively. From the 200 isolates, 68 solubilized P-Ca and 47 P-Al, and 32 isolates solubilized both P-Ca and P-Al. The AIA production significantly increased (p <0,01) with tryptophan quantities added in the medium for 19 of the 92 isolates tested in the experiment. It was observed production of dry matter and nodule number and mass superior simbiotic to the control treatment and similar to the fertilized treatment for various rhizobia isolates. The 20 selected isolates evaluated presented high genotypic diversity, with the derived dendrogram PCR-RFLP profiles showing that they can be divided inside two main genders, Rhizobium and Bradyrhizobium. Associating the results of simbiotic efficiency and nodulation, it was observed that the isolates of rhizobia from Amazonian soils presented good results, and they can be recommended for tests of agronomic efficiency for cowpea bean. / Para aumentar a contribuição de rizóbia na nutrição e desenvolvimento de plantas é necessário desenvolver pesquisas de seleção de estirpes mais eficientes quanto à fixação do N2. Este trabalho teve como objetivos, realizar a caracterização morfológica de isolados de rizóbio oriundos de solos amazônicos; avaliar em laboratório, a tolerância à acidez e Al tóxico, a capacidade de solubilização de fosfato de cálcio (P-Ca) e alumínio (P-Al), a produção de acido indol-acético (AIA); a capacidade de isolados em induzirem nodulação e fixarem nitrogênio sob as condições de acidez e baixa fertilidade dos solos regionais em casa-de-vegetação; caracterizar geneticamente os isolados selecionados usando a técnica de PCR-RFLP. Os testes de infectividade mostraram que houve aumento significativo na biomassa de caupi. Quanto à caracterização fenotípica, os 200 isolados mostraram uma grande diversidade. Dentre estes, 165 e 127 isolados apresentaram elevada tolerância nos meios de cultura com pH 4,5 e pH 4,5 + Al, respectivamente. Dos 200 isolados testados, 68 solubilizaram P-Ca e 47 P-Al, sendo que 32 solubilizaram tanto o P Ca quanto o P Al. A produção de AIA aumentou significativamente com as doses de triptofano adicionadas ao meio (p<0,01) para 19 dos 92 isolados testados no experimento. Observou-se produção de matéria seca, número e massa seca dos nódulos e acúmulo de nitrogênio superiores ao tratamento testemunha e similares ao tratamento adubado para vários isolados de rizóbia. Os 20 isolados selecionados e avaliados apresentaram alta diversidade genotípica, onde o dendrograma derivado de perfis de PCR-RFLP mostrou que podem ser divididos dentro de dois gêneros principais, Rhizobium e Bradyrhizobium. Associando-se os resultados de eficiência simbiótica e nodulação, observou-se que os isolados de rizóbio de solos da Amazônia apresentaram bom desempenho e podem ser recomendados para testes de eficiência agronômica em feijão caupi.

Abstract The releases of chlorinated volatile organic compounds (CVOCs) are controlled by strict regulations setting high demands for the abatement systems. Low temperature catalytic oxidation is a viable technology to economically destroy these often refractory emissions. Catalysts applied in the oxidation of CVOCs should be highly active and selective but also maintain a high resistance towards deactivation. In this study, a total of 33 different γ-Al2O3 containing metallic monoliths were studied in dichloromethane (DCM) and 25 of them in perchloroethylene (PCE) oxidation. The active compounds used were Pt, Pd, Rh or V2O5 alone or as mixtures. The catalysts were divided into three different testing sets: industrial, CVOC and research catalysts. ICP-OES, physisorption, chemisorption, XRD, UV-vis DRS, isotopic oxygen exchange, IC, NH3-TPD, H2-TPR and FESEM-EDS were used to characterise the catalysts. Screening of the industrial catalysts revealed that the addition of V2O5 improved the performance of the catalyst. DCM abatement was easily affected by the addition of VOC or water, but the effect on the PCE oxidation was only minor. Based on these screening tests, a set of CVOC catalysts were developed and installed into an industrial incinerator. The comparison between the laboratory and industrial scale studies showed that DCM oxidation in an industrial incinerator could be predicted relatively well. Instead, PCE was always seen to be oxidised far better in an industrial unit indicating that the transient oxidation conditions are beneficial for the PCE oxidation. Before starting the experiments with research catalysts, the water feed was optimised to 1.5 wt.%. Besides enhancing the HCl yields, water improved the DCM and PCE conversions. In the absence of oxygen, i.e. during destructive adsorption, the presence of water was seen to have an even more pronounced effect on the HCl formation and on the catalysts’ stability. In the DCM oxidation, the addition of the active compound on the catalyst support improved the selectivity, while the enhancing effect on the DCM conversion was only small. The high acidity together with the increased reducibility was seen to lead to an active catalyst. Among the research catalysts Pt/Al2O3 was the most active in the DCM oxidation. With PCE the addition of the active compound proved to be very beneficial also for the PCE conversion. Now Pt and Pd supported on Al2O3-CeO2 were the most active. The enhanced reducibility was seen to be the key feature of the catalyst in PCE oxidation. / Tiivistelmä Klooratuille orgaanisille hiilivedyille (CVOC) on asetettu tiukat päästörajoitukset niiden haitallisten vaikutusten takia. Tästä johtuen myös puhdistusmenetelmien tulee olla tehokkaita. Katalyyttinen puhdistus on teknologia, jolla nämä usein vaikeasti käsiteltävät yhdisteet voidaan taloudellisesti tuhota. Käytettävien katalyyttien tulee olla aktiivisia ja selektiivisiä sekä hyvin kestäviä. Tässä työssä tutkittiin yhteensä 33 erilaista γ-Al2O3-pohjaista hapetuskatalyyttiä metyleenikloridin (DCM) käsittelyssä, niistä 25 testattiin myös perkloorietyleenin (PCE) hapetuksessa. Aktiivisina metalleina katalyyteissä käytettiin platinaa, palladiumia, rhodiumia ja vanadiinia yksin tai seoksina. Katalyytit jaettiin kolmeen ryhmään: teolliset-, CVOC- ja tutkimuskatalyytit. Aktiivisuuskokeiden lisäksi katalyyttejä karakterisoitiin ICP-OES-, fysiorptio-, kemisorptio-, XRD-, UV-vis DRS-, isotooppivaihto-, IC-, NH3-TPD-, H2-TPR- ja FESEM-EDS-pintatutkimusmenetelmillä. Koetulokset osoittivat, että vanadiini paransi teollisuuskatalyyttien aktiivisuutta ja selektiivisyyttä. VOC-yhdisteen tai veden lisäys paransi DCM:n hapettumista, mutta PCE:n hapettumiseen niillä ei ollut vaikutusta. Testien perusteella kehitettiin CVOC-katalyytit, jotka asennettiin teolliseen polttolaitokseen. Laboratoriossa ja teollisuudessa tehdyissä testeissä havaittiin, että DCM:n hapettuminen oli laboratoriokokeiden perusteella ennustettavissa. Sen sijaan PCE hapettui teollisuudessa aina paljon paremmin kuin laboratorio-olosuhteissa. Tämä osoittaa, että muuttuvat hapettumisolosuhteet vaikuttivat positiivisesti PCE:n hapettumiseen. Veden määrä syöttövirrassa optimoitiin 1,5&#160;%:iin ennen tutkimuskatalyyttien testausta. Selektiivisyyden lisäksi vesi paransi DCM:n ja PCE:n konversiota. Hapettomissa olosuhteissa, ts. tuhoavien adsorptiokokeiden aikana, vesi paransi reaktion selektiivisyyttä HCl:ksi ja CO2:ksi vielä entisestään. Tämän lisäksi vesi lisäsi katalyytin stabiilisuutta. DCM:n hapetuksessa aktiivisen metallin lisäys paransi selektiivisyyttä, mutta sen sijaan vaikutus DCM:n konversioon oli hyvin pieni. Tulokset osoittivat, että aktiivisella DCM:n hapetuskatalyytillä tulee olla korkea happamuus ja hyvä pelkistyvyys. Pt/Al2O3 oli testatuista tutkimuskatalyyteistä aktiivisin. PCE:n hapetuksessa aktiivisen metallin lisäys paransi selektiivisyyden lisäksi huomattavasti myös konversiota. Katalyytin lisääntyneen pelkistymiskyvyn todettiin olevan keskeisin ominaisuus PCE:n hapettumisessa. Pt/Al2O3-CeO2 ja Pd/Al2O3-CeO2 olivat tutkimuskatalyyteistä aktiivisimpia.

Les glioblastomes sont des tumeurs primaires du cerveau les plus malignes. L’identification des cellules souches cancéreuses de glioblastome (CSGs) a transformé notre vision globale des glioblastomes en révélant une hiérarchie cellulaire au sein de ces tumeurs. Les CSGs sont douées de propriétés d’auto-renouvellement, de différenciation et peuvent entrer en quiescence. Elles sont considérées comme les cellules entretenant les tumeurs, responsables de leur dissémination et des rechutes après traitement. La découverte des CSGs a conduit à un changement de paradigme dans le développement des thérapies anticancéreuses, avec la nécessité de cibler dans le traitement non seulement les cellules de la masse tumorale, mais aussi les CSGs. Un criblage différentiel de la chimiothèque Prestwick réalisé au laboratoire a permis d’identifier le bisacodyl comme une molécule présentant une cytotoxicité spécifique sur les CSGs en quiescence.Cette thèse présente un travail sur la caractérisation des CSGs, la compréhension du mode d’action du bisacodyl, ainsi que l’évaluation de son potentiel thérapeutique sur un modèle 3D in intro et des modèles in vivo. / Glioblastomas are the most malignant primary brain tumors. The identification of glioblastoma stemcells (GSCs) has transformed our comprehension of those tumors by revealing a hierarchical organization. GSCs can self-renew, differentiate and enter into a quiescent state. They are considered as cells which fuel and as the main culprits of tumor relapse. The discovery of GSCs triggered a change in paradigm for cancer therapy. Indeed to gain in efficacy, therapies need to target, not only the cells forming the bulk of the tumor, but also GSCs particularly resistant and endowed with a high tumorigenic potential. Chemical screening of the Prestwick chemical library in our laboratory, unveiled bisacodyl with a specific activity on quiescent GSCs.This thesis presents work on the characterization of GSCs, study of the mode of action of bisacodyl on GSCs, as well as a preclinical evaluation of bisacodyl on a 3D model in vitro and animal models in vivo.

Les glioblastomes (GBM) sont les formes les plus agressives de tumeurs gliales avec une survie médiane des patients traités n’excédant pas 2 ans. Ce mauvais pronostic est dû, entre autres, à l’hétérogénéité de ces tumeurs avec la présence de cellules souches cancéreuses (CSCs) en prolifération ou quiescentes, particulièrement résistantes aux traitements conventionnels. Cibler ces cellules au sein du microenvironment tumoral hypoxique et acides fait donc partie des thérapies d’avenir des GBMs. Le laxatif bisacodyl a été identifié par criblage de la chimiothèque Prestwick comme un composé induisant la mort par nécrose des CSCs de glioblastome (GSCs en prolifération et en quiescence), uniquement dans des conditions de faible acidité retrouvées également au sein des tumeurs. Une activité antitumorale in vivo a également été démontrée pour ce composé. Cette thèse présente l’identification du mode d’action du bisacodyl dans les GSCs. Celui-ci implique la serine/thréonine kinase WNK1 et ses partenaires, les kinases Akt et SGK1 et des co-transporteurs Na+/HCO3- NBC. Nos résultats ont également révélé un rôle de WNK1 dans la physiopathologie des GSCs. / Glioblastoma (GBM), the most aggressive glial tumor, is currently incurable with a very short-term patient survival (< 2 years). The heterogeneity of GBM and the presence of highly resistant proliferating and quiescent cancer stem-like cells (CSCs), is largely responsible for poor prognosis in this disease. Thus, new approaches targeting glioblastoma CSCs (GSCs), within the acidic/hypoxic tumor microenvironment, are promising strategies for treating GBM. The laxative bisacodyl was identified in a high throughput screening of the Prestwick chemical library as a compound inducing necrotic cell death in proliferating and quiescent GSCs only in acidic microenvironments similar to those found in tumors. Bisacodyl was further shown to induce tumor shrinking and to increase survival in in vivo GBM models. In this thesis work, we identify bisacodyl’s mechanism of action in GSCs. This mechanism involves the serine/threonine kinase WNK1 and its signaling partners including protein kinases Akt and SGK1 and NBC Na+/HCO3- cotransporters. Our data also highlight a previously unknown role of WNK1 in GSC physiopathology.

Abstract As human activities are increasingly affecting natural communities, many communities are impacted by multiple stressors and their interactions. Understanding how natural and anthropogenic stressors act individually and in concert is essential for managing and conserving natural ecosystems efficiently. In this thesis I studied how geology-related natural acidity, land drainage and their interaction affect biological communities and leaf decomposition in boreal headwater streams. I further assessed the concordance of communities along natural and anthropogenic stressor gradients. As model organisms, I used benthic diatoms, bryophytes, invertebrates and leaf-decomposing fungi. I showed that geology-related natural acidity constitutes a strong environmental filter for stream communities, reducing species richness and changing community composition. Community concordance was also generally strongest along the natural acidity gradient. However, natural acidity mostly did not homogenize communities nor did it affect leaf decomposition by fungi. Effects of peatland drainage differed between the two stream types, being mainly sedimentation in the circumneutral streams and increasing metal concentrations in the acid streams. Overall, changes in community composition were better able than pure species richness to track single stressor impacts. Furthermore, fungal assemblages were more homogeneous and decomposition rates slower in drained acidic sites than in any other stream type. Thus the drainage-induced shift in water chemistry in the acidic streams seems to constitute an even stronger environmental filter than sedimentation. Conservation planning needs to give special attention to these vulnerable, naturally stressful ecosystems. / Tiivistelmä Ihmistoiminnan vaikuttaessa yhä enemmän luonnon elinympäristöihin eliöyhteisöihin kohdistuu usein samanaikaisesti monenlaisia paineita. Ekosysteemien tehokas hoitaminen ja suojelu edellyttävät tarkkaa tietoa siitä, miten luonnollinen stressi ja ihmistoiminta yhdessä ja erikseen vaikuttavat ekosysteemeihin. Väitöskirjassani tutkin, kuinka geologiasta johtuva luonnollinen happamuus ja metsäojitus vaikuttavat boreaalisten purojen eliöyhteisöihin ja lehtikarikkeen hajotukseen. Tarkastelin myös eliöryhmien yhdenmukaisuutta ihmistoimintagradientilla ja luonnollisella stressigradientilla. Malliorganismeinani olivat piilevät, vesisammalet, pohjaeläimet ja hajottajasienet. Väitöskirjassani osoitan, että geologiasta johtuva puroveden happamuus toimii merkittävänä ympäristösuodattimena purojen eliöyhteisöille vähentäen lajirunsautta ja muokaten lajistoa. Myös eliöryhmien lajistovaihtelu oli yhdenmukaisinta luonnollisella happamuusgradientilla. Toisaalta luonnollinen happamuus ei vaikuttanut merkittävästi lehtikarikkeen hajotukseen tai purojen väliseen sieniyhteisöjen monimuotoisuuteen. Metsäojituksen fysikaalis-kemiallinen vaikutus erosi purotyypeittäin: pH-neutraaleissa puroissa ojitus pääosin lisäsi pohjan hiekoittumista, kun taas happamissa puroissa veden metallipitoisuudet kasvoivat entisestään. Yleisesti ottaen sekä luonnollisen happamuuden että metsäojituksen vaikutukset näkyivät parhaiten muutoksina eliöyhteisöjen lajikoostumuksessa. Lisäksi ojitetuissa happamissa puroissa hajottajasieniyhteisöjen lajistot olivat keskenään samankaltaisempia ja lehtikarikkeen hajotus hitaampaa kuin muissa purotyypeissä. Metsäojituksen aikaansaama muutos luonnollisesti happamien purojen vesikemiassa näyttää siis olevan jopa merkittävämpi ympäristösuodatin kuin pohjan hiekoittuminen. Luonnollisesti stressattujen elinympäristöjen herkkyys maankäytön muutoksille tulisikin huomioida ympäristön hoidon suunnittelussa nykyistä paremmin.

Le procédé de traitement du combustible du réacteur à sels fondus (réacteur de génération IV) est un procédé multi-étape dans lequell’extraction des actinides et des lanthanides utilise la technique d’extraction réductrice. Le développement d’un modèle analytique a montré que la mise en contact du sel combustible LiF-ThF4 avec une phase métallique constituée d'un mélange Bi-Li permet l’extraction sélective et quantitative des actinides dans un premier temps, puis l’extraction quantitative des lanthanides dans un second temps. La maitrise de ce procédé nécessite la connaissance des caractéristiques des phases salines impliquées dans le procédé. Les études des propriétés physico-chimiques des sels fluorures fondus ont permis de développer une technique de mesure de la fluoroacidité dans ces milieux via une mesure potentiométrique. Cette technique a permis d’établir un classement de différents mélanges de fluorures fondus en fonction de leur acidité relative. Par ailleurs, une méthode de détermination de la solvatation de solutés dans ces milieux a également été développée par électrochimie afin d’approfondir la connaissance du sel combustible (en particulier solvatation de ThF4 par les ions F-).L'extraction réductrice met également en jeu une phase métallique liquide. Une technique de préparation de cette phase a été développée par électro-réduction de lithium sur une électrode liquide de bismuth en milieu LiCl-LiF. Cette technique permet un bon contrôle de la fraction molaire de lithium introduite dans le bismuth, paramètre essentiel à l’efficacité de l’extraction.Enfin, afin d'optimiser le procédé général de traitement multi-étapes, des méthodes électrochimiques ont été proposées afin de régénérer les différentes phases liquides (salines et métalliques) mise en jeu lors de l’extraction. / The fuel reprocessing of the molten salt reactor (Gen IV concept) is a multi-steps process in which actinides and lanthanides extraction is performed by a reductive extraction technique. The development of an analytic model has showed that the contact between the liquid fuel LiF-ThF4 and a metallic phase constituted of Bi-Li provide firstly a selective and quantitative extraction of actinides and secondly a quantitative extraction of lanthanides. The control of this process implies the knowledge of saline phase properties. Studies of the physico-chemical properties of fluoride salts lead to develop a technique based on potentiometric measurements to evaluate the fluoroacidity of the salts. An acidity scale was established in order to classify the different fluoride salts considered.Another electrochemical method was also developed in order to determine the solvation properties of solutes in fluoride F- environment (and particularly ThF4 by F-)In reductive extraction technique, a metallic phase is also involved. A method to prepare this phase was developed by electro-reduction of lithium on a bismuth liquid cathode in LiCl-LiF melt. This technique allows to accurately control the molar fraction of lithium introduced into the liquid bismuth, which is a main parameter to obtain an efficient extraction.