L'île de la Martinique a connu l'histoire volcanique la plus complète de l'arc des Petites Antilles, de 25 Ma à l'actuel. L'hétérogénéité chimique et isotopique des laves de l'île est très importante non seulement par rapport aux autres îles de l'arc mais aussi par rapport aux autres arcs intra-océaniques. L'objectif de ces travaux est d'expliquer la variabilité géochimique des laves de la Martinique et de caractériser les processus de genèse des produits volcaniques émis sur l'île. Pour cela, nous avons effectué une étude géochimique approfondie (éléments majeurs, éléments traces, rapports isotopiques du Pb, Sr, Nd et Hf) sur des échantillons de laves représentatifs de toute l'histoire volcanique de la Martinique. Grâce à une collaboration avec Aurélie Germa et Xavier Quidelleur de l'université Orsay - Paris XI, l'étude géochimique a été couplée à une datation des laves par méthode K-Ar. Les laves martiniquaises forment des droites et hyperboles de mélanges entre pôles appauvris mantelliques et pôle enrichis crustaux. Il apparaît que deux mélanges distincts sont visibles, un premier mélange est formé par les laves « anciennes » (entre 25 et 7 Ma) et un deuxième mélange est formé par les laves « récentes » (entre 5 Ma et l'actuel). Les pôles mantelliques et les pôles crustaux impliqués dans les sources des magmas ne sont pas les mêmes avant et après 6 Ma. Ce changement de source est probablement lié au passage de la ride asismique qui a décalé la moitié nord de l'arc des Petites Antilles. L'origine de la signature crustale des laves martiniquaises est testée en comparant un modèle de mélange à la source entre des sédiments de la plaque plongeante et le coin mantellique et un modèle d'assimilation de la croûte de l'arc par les magmas mantelliques ascendants. Le modèle d'assimilation intra-crustale ne peut pas reproduire les tendances décrites par les laves alors que le modèle de mélange à la source le fait parfaitement. La comparaison entre les pôles crustaux impliqués dans les mélanges et les sédiments entrants dans la subduction indique qu'il n'y a pas de fractionnement entre le Pb, le Sr, le Nd et l'Hf ce qui implique que les sédiments sont probablement ajoutés à la source par fusion partielle et non par déshydratation. Le rapport La/Yb des laves martiniquaises apparait comme un proxy de la proportion de sédiments dans la source des magmas et non du taux de fusion partielle ou de la nature de la phase alumineuse du manteau bien que la fusion, de l'ordre de 10%, ait lieu dans la zone de stabilité du grenat. Le gradient géographique du rapport La/Yb au sein de l'île traduit donc un gradient géographique de la proportion de sédiments, et montre que la proportion de sédiments dans la source augmente avec l'éloignement à la fosse.

<p>Alternativ splicing är en process som ger upphov till att olika mRNA-sekvenser bildas från en enda gen, vilket bidrar till en ökad proteindiversitet hos organismen. Olika mRNA-sekvenser kan uppstå eftersom att det förekommer olika varianter av alternativ splicing som även kan kombineras på flera olika sätt: cassette exon (inkludering/exkludering av exon), intron retention (intronet behålls), alternative 5´splice-site choice (olika 5´ splice sites kan väljas) och slutligen alternative 3´ splice-site choice (andra 3´ splice sites kan väljas). För att alternativ splicing ska äga rum i olika pre-mRNA måste den regleras av cis-reglerande element. De cis-reglerande elementen utgörs av fyra grupper: exonic splicing enhancers (ESE), exonic splicing silencers (ESS), intronic splicing enhancers (ISE) samt intronic splicing silencers (ISS). Som namnen förtäljer finns de antingen i exoner eller introner, där de interagerar med transagerande faktorer, SR-proteiner (aktiverare) eller hnRNPs (hämmare). Alternativ splicing förekommer både i djur och i växter. Hos <em>Homo sapiens </em>genomgår över 74 % av de 25,000 gener som finns hos organismen, alternativ splicing. Däremot i växten <em>Arabidopsis thaliana</em>, genomgår endast 22 %, av den totala mängden på cirka 26,000 gener, alternativ splicing. Eftersom att processen bidrar till en ökad proteindiversitet, kommer det medföra att olika processer i organismerna påverkas, exempelvis celltillväxt, celldöd samt utvecklingen av olika sjukdomar, såsom Parkinson och cystisk fibros. Många studier har gjorts som bekräftar dess betydelse för organismerna men på grund av processens komplexitet är det fortfarande ett ämne som ständigt måste utforskas.</p><p> </p>

Integrated sequence stratigraphy and geochemistry has significantly improved our knowledge of the formation and distribution of early and late diagenetic products in North American Mississippian carbonates. Deposition of the Madison Limestone occurred in concert with a major perturbation to the global C-pool, the timing of which was constrained by comparing secular variations in the delta13C values from the Madison Limestone with limited biostratigraphy. These early constraints were then improved by peak matching of 87Sr/86Sr values from this study with European brachiopod 87Sr/86Sr. The secular variations in the delta13C values were then applied as a chronostratigraphic tool to outcrops and subsurface core. As a result, our sequence stratigraphic interpretations and knowledge regarding lateral facies variability in carbonate rocks is significantly improved. Geographic variability in the magnitude of the delta13C values is also documented along the dip-transects which suggests that marine waters experienced increasing restriction in a landward direction. These results show how local changes to the C-pool are controlled by the morphology of the depositional system which can significantly affect the original signal of the global carbon pool. The geographic variability in the delta13C and delta18O values from reservoir quality dolomites along the mid-to-upper Madison ramp suggest they also precipitated from a restricted water mass with increased salinity, temperature and alkalinity which in turn, were responsible for the distribution of massive quantities of strataform dolomite deposited during the continental transgression at the beginning of the Mississippian. Trace element and 87Sr/86Sr values from strataform dolomite suggest initial formation from Mississippian seawater and slight resetting during shallow burial diagenesis. Petrography indicates that the formation of this dolomite ceased in the shallow burial environment, between the Mississippian and Permian. These dolomites are cross-cut by comparatively small volumes of geothermal-hydrothermal dolomite associated with Laramide-age breccias and fractures. Tectonic-hydrothermal activity associated with the Laramide Orogeny was responsible for late stage calcite cemented fractures and breccias which cross-cut all carbonate rocks discussed in this thesis. Radiogenic 87Sr/86Sr, depleted delta18O and enriched delta13C values and the hottest fluid inclusions measured in this study suggest the late stage calcite formed in the hydrothermal environment and under the most open-system and water-dominated conditions. Tectonic-diagenesis is ultimately responsible for establishing vertical barriers in the otherwise porous and permeable strataform dolomites.

In the mid-1990’s, the global computer network known as the Internet was introduced in Sweden. With this study, we are shining a light on the entrance of Swedish Public Service media on the Internet. The two major Swedish Public Service companies Sveriges Television (“Swedish Television”, also called SVT) and Sveriges Radio (“Swedish Radio”, also called SR) are included in this study. SR published its first website in 1994 and the site featured a presentation of the results from the Swedish parliament elections of that year. SVT published its first website in 1995, when the company wanted to find a way to develop the classic teletext. The reason why we are studying these companies is that we wanted to find out why two publically funded companies decided to enter the new and relatively unknown Internet platform at a time when only three percent of the Swedish population had Internet access at home. We have interviewed technicians and board members working for either SR or SVT at the time surrounding their entry on the Internet and we have also accessed board documents and other written information from the companies. The study shows that both SR and SVT had an early presence on the Internet but without really investing. The respective boards were unsure about the usefulness of the new platform and the technicians were working without getting, according to themselves, enough time and money. The situation changed at the beginning of the 21st century, after the timeframe of our study.

The aim of this study has been to analyse the effects of state subsidies within agriculture. The goal of these policies was to build up long-term sound and profitable farms by means of both general and selective support measures. The investments affecting structure gave rise to the following questions: (a) What were the effects on a farm of a given type of aid? (b) How were the farms and the surrounding community affected? (c) In what respect was a desirable effect achieved, and in what respect were the results problematical? The investigation was carried out in three municipalities in Norrland, and considered three different forms of subsidy (SR-, A- and B-support) which were utilized during the years 1961-1978. In addition to these so-called "subsidized farms", a similar number of "comparative farms" that had not received support were selected. In all, 650 farms were investigated. The evaluation was mainly divided into five areas of interest: (a) Farm reconstruction, (b) Farm development, (c) The farmers, (d) Economic effects, (e) Social effects in the locality. The principal findings were as follows: (1) SR- and A-supported farms were characterized by farmers who were relatively young, had good education and who used a portion of their working-hours for carrying out organizational measures. The comparative farms were distinguished rather by older farmers with less education and with a higher degree of employment outside the farm. (2) All of the SR-and B-supported farms had survived. Some A-supported farms were abandoned, while the number of comparative farms was greatly reduced. (3) All types of subsidized farms exhibited growth in their areas of arable land and forest and in their stock of milk cows, whereas the comparative farms were relatively unchanged. (4) Improved production results within crop husbandry could be derived simultaneously from the increased use of pipe drainage, shorter periods between ploughing, new methods of harvesting, etc. Within all these areas the subsidized farms had higher proportions of improvements than the comparative farms. (5) Since SR-farms in particular (but even A-farms) financed their rationalization measures by means of bank loans, they all became extremely sensitive to risks. In thi s way they all too easily ended up with economic difficulties when major increases in interest rates or changes in costs or revenues occurred. (6) In the short term the rationalization of the size of subsidized farms had little effect on outmigration from the areas concerned. (7) The households were larger on subsidized farms than in the comparative group. This meant that the subsidized farms, which were increasing their relative share of the population, also comprised a stabilizing factor in a locally-dependent service sector. / digitalisering@umu

The 87Rb-86Sr system is a widely used long-lived isotope geochronometer. 87Rb, the naturally occurring radioactive isotope of Rb, undergoes beta-decay to stable 87Sr with a half-life of approximately 50 Ga. Decay of 87Rb to 87Sr results in variable 87Sr/86Sr in minerals with different Rb/Sr, and measurement of 87Rb/86Sr and 87Sr/86Sr allows for the determination of the age of the rock. Accurate ages depend both on the quality of the isotopic analysis and on the accuracy of the 87Rb decay constant, lambda87. Although the currently accepted value for lambda87 of 1.42 × 10-11a-1 has been in use for over 30 years, there is growing evidence that it is not accurate. Recent attempts to refine lambda87 and its precision have not reached a consensus. This thesis describes a new experiment to measure lambda87 by 87Sr accumulation over a period of about 30 years, and the preparation of a 84-86Sr double-spike in conjunction with that experiment. Radiogenic 87Sr produced in aliquots of a RbClO4 salt was measured by isotope dilution thermal ionization mass spectrometry. An average of 31 measurements yields a value of 1.398 ± 0.003 × 10-11a-1 . This requires a substantial revision from the previously accepted decay constant and makes Rb-Sr ages calculated with it 1.5% older. A Rb-Sr and U-Pb isotopic chronometry study was carried out on thirteen ordinary chondrites – the most common type of meteorite, the origin and history of which are still unclear. Some meteorites appear disturbed, possibly by recent shock during breakup of the parent body, whereas others yielded accurate and precise U-Pb and Pb-Pb ages. For example, L5 Elenovka yielded distinct ages for silicates (4555 Ma) and phosphates (4535 Ma), allowing the cooling rate of this meteorite from approximately 1055 K to 759 K to be constrained to 15 ± 3 K/Ma. Rb-Sr yielded less precise ages than U-Pb, but using the new decay constant allows accurate comparison between the two methods. This study creates a firm foundation for future studies in thermal history of chondrites and terrestrial metamorphic complexes using Rb-Sr together with other isotopic chronometers.

Glioblastoma multiforme (GBM) is the most aggressive and most common primary brain tumor in adults accounting for 50-60% of primary brain tumors. The prognosis for patients with GBM remains poor and treatment is mainly palliative with a mean survival time of less than one year. Radiotherapy is used extensively in the management of glioblastoma either alone or in combination with surgery and/or chemotherapy. However, this tumor is one of the most resistant tumors to radiotherapy thus limiting the benefit of this form of treatment. <p>Studies have shown that malignant tumors have a high content of glutathione an antioxidant responsible for protecting the cells against damage from free radicals (mainly superoxide, hydroxyl and hydrogen peroxide). It is well established that glutathione, by neutralizing these free radicals plays a major role in radioresistance. Glioblastoma has relatively high levels of glutathione. In this study, by reducing the glutathione content of glioblastoma in a rat model, we were able to investigate the effect of this reduction in enhancing the effect of radiotherapy as a form of treatment for glioblastoma multiforme in a rat model. <p>By injecting L-Buthionine-SR-Sulfoximine (BSO) in to the tumor tissue, the glutathione content of the tumor was reduced by about 70% of its initial value. When administered into the tumors 2 hours prior to radiotherapy the animals so treated had a significantly longer median survival time compared with animals that received radiotherapy alone.

Diamond Blackfan Anemia (DBA) is a congenital disorder characterized by a specific reduction in erythroid progenitor cells. Approximately 55% of patients have heterozygous mutations in ribosomal protein with 25% of these mutations in RPS19. However, it is unclear how a defect in ribosomal proteins specifically disrupts erythroid development. FLVCR1, a heme exporter, has been implicated as a potential DBA factor. FLVCR1 is essential for erythropoiesis as its disruption leads to apoptosis and disrupted erythroid differentiation. Though no FLVCR1 mutations have been found in DBA patients, our lab has shown that it is aberrantly spliced in DBA erythroid cells. Using RPS19 reduced K562 erythroid cells, I found that disruption of RPS19 leads to aberrant FLVCR1 splicing, disrupted erythropoiesis and reduced Tra2-β, ASF2 and SRp30c protein expression. This was specific to DBA as I did not find these features in a cell culture model of Shwachmann Diamond Syndrome, another ribosomal disorder.

Diamond Blackfan Anemia (DBA) is a congenital disorder characterized by a specific reduction in erythroid progenitor cells. Approximately 55% of patients have heterozygous mutations in ribosomal protein with 25% of these mutations in RPS19. However, it is unclear how a defect in ribosomal proteins specifically disrupts erythroid development. FLVCR1, a heme exporter, has been implicated as a potential DBA factor. FLVCR1 is essential for erythropoiesis as its disruption leads to apoptosis and disrupted erythroid differentiation. Though no FLVCR1 mutations have been found in DBA patients, our lab has shown that it is aberrantly spliced in DBA erythroid cells. Using RPS19 reduced K562 erythroid cells, I found that disruption of RPS19 leads to aberrant FLVCR1 splicing, disrupted erythropoiesis and reduced Tra2-β, ASF2 and SRp30c protein expression. This was specific to DBA as I did not find these features in a cell culture model of Shwachmann Diamond Syndrome, another ribosomal disorder.

The 87Rb-86Sr system is a widely used long-lived isotope geochronometer. 87Rb, the naturally occurring radioactive isotope of Rb, undergoes beta-decay to stable 87Sr with a half-life of approximately 50 Ga. Decay of 87Rb to 87Sr results in variable 87Sr/86Sr in minerals with different Rb/Sr, and measurement of 87Rb/86Sr and 87Sr/86Sr allows for the determination of the age of the rock. Accurate ages depend both on the quality of the isotopic analysis and on the accuracy of the 87Rb decay constant, lambda87. Although the currently accepted value for lambda87 of 1.42 × 10-11a-1 has been in use for over 30 years, there is growing evidence that it is not accurate. Recent attempts to refine lambda87 and its precision have not reached a consensus. This thesis describes a new experiment to measure lambda87 by 87Sr accumulation over a period of about 30 years, and the preparation of a 84-86Sr double-spike in conjunction with that experiment. Radiogenic 87Sr produced in aliquots of a RbClO4 salt was measured by isotope dilution thermal ionization mass spectrometry. An average of 31 measurements yields a value of 1.398 ± 0.003 × 10-11a-1 . This requires a substantial revision from the previously accepted decay constant and makes Rb-Sr ages calculated with it 1.5% older. A Rb-Sr and U-Pb isotopic chronometry study was carried out on thirteen ordinary chondrites – the most common type of meteorite, the origin and history of which are still unclear. Some meteorites appear disturbed, possibly by recent shock during breakup of the parent body, whereas others yielded accurate and precise U-Pb and Pb-Pb ages. For example, L5 Elenovka yielded distinct ages for silicates (4555 Ma) and phosphates (4535 Ma), allowing the cooling rate of this meteorite from approximately 1055 K to 759 K to be constrained to 15 ± 3 K/Ma. Rb-Sr yielded less precise ages than U-Pb, but using the new decay constant allows accurate comparison between the two methods. This study creates a firm foundation for future studies in thermal history of chondrites and terrestrial metamorphic complexes using Rb-Sr together with other isotopic chronometers.