Ziel dieser Dissertationsschrift war es, die Effekte des oxidativen Stresses in Form von oxLDL auf die Expression der atherogenen Scavenger-Rezeptoren CD36, SR-BI, des Transkriptionsfaktors PPARγ und pro-inflammatorischer Zytokine zu untersuchen. Die durchgeführten Untersuchungen beruhen auf der Annahme, dass modifizierte LDL durch Induktion der genannten Scavenger-Rezeptoren und nachfolgende unregulierte Aufnahme in Makrophagen mit Bildung von Schaumzellen entscheidend zur Entwicklung einer Atherosklerose beitragen. Dabei scheint vor allem die im Rahmen des oxidativen Stresses auftretende oxidative Modifizierung der LDL eine Rolle zu spielen. Oxidativem Stress wird in der Pathogenese vieler Krankheiten eine Bedeutung zugesprochen, deren pathobiochemische Grundlagen jedoch noch nicht vollständig geklärt sind und zu deren Erforschung diese Dissertation beitragen sollte. Im ersten Versuchsteil wurden deshalb in vitro – Versuche zu Expressionsraten oben genannter Rezeptoren durchgeführt. Dabei wurden Hypochlorit-oxidierte LDL genutzt, denen im Gegensatz zu den in vielen Versuchen verwendeten Kupfer-oxidierten LDL auch in vivo eine pathophysiologische Relevanz zukommt. Desweiteren ist bekannt, dass Diabetiker neben einem hohen Risiko an Atherosklerose zu erkranken, auch laborchemisch erhöhte Marker des oxidativen Stresses zeigen, inklusive einer gesteigerten Menge an zirkulierenden oxLDL. Im zweiten Versuchsteil wurde deshalb ex vivo untersucht, inwiefern LDL, gewonnen von Patienten im prädiabetischen Stadium der gestörten Glukosetoleranz, ähnliche Auswirkungen auf die Expression von Scavenger-Rezeptoren zeigen, wie in den mit Hypochlorit-oxidierten LDL durchgeführten in vitro - Untersuchungen beobachtet werden konnte. Es zeigte sich, dass CD36, der für die Aufnahme von oxidativ modifizierten LDL als der bedeutendste Rezeptor gilt, durch Hypochlorit-oxidierte LDL stark induziert wird. Zusammengenommen mit der ebenfalls beobachteten Heraufregulation des Transkriptionsfaktors PPARγ, sowie der signifikanten Korrelation beider Gene kann damit für Hypochlorit-oxidierte LDL eine atherogene Wirkung nachgewiesen werden. Die Ergebnisse bestätigen zudem die von Nagy und Tontonoz zuerst beschriebene Feed-Forward-Schleife, bei der oxidative LDL über Induktion und Aktivierung von PPARγ die Expression von CD36 erhöhen, mit nachfolgender unregulierter Aufnahme von Cholesterolestern in Makrophagen und subsequenter Bildung von Schaumzellen. Die Versuche zeigen zudem, dass der Scavenger-Rezeptor SR-BI, obwohl strukturell stark mit CD36 verwandt, eine differentielle Regulation aufweist und durch oxidativ modifizierte LDL signifikant supprimiert wird. Eine Induktion durch PPARγ, wie sie eindrucksvoll bei CD36 beobachtet werden kann, ist für SR-BI in den in vitro - Versuchen nicht vorhanden. Mit der in vielen Studien SR-BI, jedoch nicht CD36 zugesprochenen Funktion als Vermittler des HDL-Membranstransports gehen damit auch unterschiedliche Regulationsmechanismen einher. Die Ausschüttung pro-inflammatorischer Zytokine in murinen Makrophagen wurde durch Hypochlorit-oxidierte LDL im Vergleich mit nativen LDL signifikant vermindert, eine Assoziation mit dem Transkriptionsfaktor PPARγ konnte nicht gefunden werden. Die für die ex vivo - Versuche untersuchten Gruppen der insgesamt 40 Probanden mit gestörter und normaler Glukosetoleranz wiesen, mit Ausnahme eines pathologischen Glukosetoleranztests für IGT-Patienten, in der klinischen Untersuchung, beim Vergleich der Laborparameter, ebenso wie in der Zusammensetzung der LDL keine signifikanten Unterschiede auf. Dennoch fand sich eine signifikante Erhöhung der CD36-Expression in Makrophagen schon nach einstündiger Inkubation mit LDL aus IGT-Patienten im Vergleich zu LDL von Probanden mit normaler Glukosetoleranz. Für die Expressionsraten von SR-BI, PPARγ und die Zytokinausschüttung konnten nur marginale Unterschiede zwischen den Probandengruppen erfasst werden. Auch in den ex vivo – Untersuchungen wiesen eine insignifikante PPARγ - Erhöhung und eine positive Korrelation zwischen PPARγ und CD36 auf die Existenz und Aktivierung der beschriebenen atherogenen Feed-Forward-Schleife auch in IGT-Patienten hin. Zusammenfassend unterstreicht diese Dissertationsschrift die Bedeutung des oxidativen Stresses in der Entwicklung der Atherosklerose, indem erstmals auch für das pathophysiologisch relevante Hypochlorit-oxidierte LDL eine deutliche Expressionssteigerung des Scavenger-Rezeptors CD36 und des Transkriptionsfaktor PPARγ nachgewiesen werden konnte. Zudem zeigen die Experimente, dass bereits bei Patienten im Vorstadium des Diabetes mellitus Typ 2 funktionelle Veränderungen der LDL eingetreten sind, die zu einer verstärkten Atherosklerose führen können und die denen gleichen, die durch künstlich oxidierte LDL ausgelöst werden. Die Versuche liefern damit eine mögliche Erklärung für den bereits epidemiologisch nachgewiesenen Zusammenhang zwischen oxidativem Stress, Atherosklerose und Diabetes mellitus.

Traditionellt utvärderas effekter av kognitiv träning med objektiva prestationsmått. Syftet med uppsatsen var att undersöka självskattad exekutiv funktion som ett alternativt mått för att utvärdera effekter av kognitiv träning. Som utfallsmått valdes The behavior rating inventory of executive functioning - self report (BRIEF-SR). Vidare användes blandad design med för- och eftermätning samt tre oberoende grupper. Gymnasieelever (n = 63) delades in i; aktiv träningsgrupp, aktiv placebogrupp och passiv kontrollgrupp. Tränings- och placebogruppen genomförde datoriserad kognitiv träning med respektive utan adaptiv svårighetsgrad. ANCOVA med arbetsminneskapacitet som kovariat visade inga signifikanta träningseffekter på självskattade exekutiva funktioner, oavsett grupptillhörighet. Sammantaget kan BRIEF-SR vara ett lämpligt instrument vid utvärdering av kognitiv träning när ekologisk validitet prioriteras. Resultaten diskuteras avseende inverkan av tid mellan för- och eftermätning, population och förväntanseffekter. / Performance based measures have been the Golden standard when evaluating effects of cognitive training. By using The Behavior Rating Inventory of Executive Functioning-Self Report (BRIEF-SR), this thesis aimed to explore self- rating scales as an alternative when evaluating effects of cognitive training. A sample of high school students (n = 63) and a mixed- effect model with pre- and post-measurements were chosen. The students were divided into three groups: active training, training with placebo or passive control. The two groups in training practiced with a computerized cognitive training program. The two training groups practiced with an adaptive and non-adaptive computer program, respectively.  With working memory as covariate ANCOVA reported no significant effects on self-rated executive functions independent of group condition. In sum, if ecological validity is of priority BRIEF-SR can be considered when measuring effects following cognitive training. In addition the results are discussed with regards to time between pre- and post-measurements, population and effects of expectancy. / Effekter av kognitiv träning på skolprestationer och självreglering av beteende (dnr 1,2009/0 018,5-0)

Functional crystalline oxides with perovskite structure have a wide range of electrical properties such as ferroelectric, ferromagnetic, and superconductive, as well as unique properties that make them suited for a wide variety of applications including electro-optics, high-k dielectrics, and catalysis. Therefore, in order to realize the potential of perovskite oxides it is desirable to integrate them with semiconductors. Due to the high surface energy of oxides compared to that of semiconductors and the low number of oxides that are thermodynamically stable against SiO₂ formation, it has been extremely difficult to integrate epitaxial oxides with Si directly. However, in 1998, McKee and co-workers finally succeeded in depositing SrTiO₃ on Si directly using a Sr template via molecular beam epitaxy. This breakthrough opened the possibility of integrating the perovskite oxides with Si to realize potential device applications. In this dissertation, alkaline earth metal (Sr and Ba) templates on semiconductors, which enable epitaxial growth of complex oxides on semiconductors, are investigated using molecular beam epitaxy (MBE) for growth and in-situ X-ray/ultraviolet photoemission spectroscopy (XPS/UPS) for the electronic structure analysis. An epitaxial layer of SrTiO₃ on Si using such alkaline earth templates is used as a pseudo-substrate for the integration of perovskite oxides on Si. Through the use of post-deposition annealing as a function of oxygen pressure and annealing time, the strain relaxation behavior of epitaxial SrTiO₃ films grown on Si is also investigated to determine how the SiO₂ interlayer thickness affects the SrTiO₃ lattice constant. This ability to control strain relaxation can be used as a way to manipulate the properties of other perovskite oxides grown on SrTiO₃/Si. Additionally, SrTiO₃ can be made conductive by doping with La. Conductive SrTiO₃ can be used as a thermoelectric, a transparent conductive layer, and a quantum metal layer in a quantum metal field-effect transistor (QMFET). The structural, electrical, and optical properties of strained conductive La-doped SrTiO₃ are studied in order to understand the relation between elastic strain and electrical properties for electronic device applications. Oxide quantum well systems based on LaAlO₃/SrTiO₃ are also investigated using spectroscopic ellipsometry to understand how the quantum well layer structure affects the electronic structure. Such quantum well systems are good candidates for the monolithic integration of functional perovskites on semiconductors. Oxides quantum wells can be used in various device applications such as in quantum well cascade lasers, laser diodes and high performance transistors. As part of the growth optimization for high quality complex oxide heterostructures, the surface preparation of SrTiO₃ substrates using several different methods was also extensively studied using angle-resolved photoemission spectroscopy (ARPES). We found that acid-free water-based surface preparation is actually more effective at removing SrOx̳ crystallites and leaving the surface TiO₂-terminated compared to the more commonly used acid-based methods. / text

Les laves provenant de l’arc des Petites Antilles sont caractérisées par une grande variabilité chimique et leurs compositions isotopiques suggèrent une contribution variable de matériel crustal ancien dans leur genèse. L’arc des Petites Antilles est également caractérisé par une zonation chimique nord-sud, les laves des îles du sud présentant généralement des signatures isotopiques crustales plus fortes que celles des îles du nord. Nous avons tenté dans cette étude d’établir s’il existe des variations de la composition chimique des sédiments entrant en subduction le long de l’arc, et si d’éventuels changements de leur composition peuvent expliquer les variations chimiques observées au sein des laves. Pour ce faire, nous avons réalisé une étude géochimique approfondie (majeurs, traces, isotopes du Sr, du Nd, de l’Hf et du Pb) du flux sédimentaire potentiellement entrant dans la zone de subduction à différentes latitudes. L’échantillonnage comprend des sédiments forés au niveau des sites 543 (nord de l’arc) et 144 (extrême sud de l’arc) lors des campagnes DSDP 78A et 14 respectivement, et des sédiments provenant de l’île de la Barbade (sud de l’arc). Les échantillons présentent une grande hétérogénéité lithologique correspondant globalement à un mélange en proportion variable entre une composante détritique et une composante biogénique (siliceuse ou carbonatée). De plus, au niveau du site 144, des niveaux très riches en matière organique (black shales) datant du Cénomanien supérieur au Santonien (~ 95 à 84 Ma) ont été forés. Ces formations correspondent à l’enregistrement des Oceanic Anoxic Events 2 et 3. Nous avons montré que la « dilution » variable de la fraction détritique par la composante biogénique est le facteur qui contrôle largement les variations de concentrations en éléments traces observées. De plus, nous avons révélé un enrichissement en U extrêmement important au sein des black shales du site 144. Les signatures isotopiques de l’Hf, du Nd et du Pb sont dominées par la composante détritique, alors que celle du Sr, dans le cas d’échantillons riches en carbonates est dominée par celle de l’eau de mer. Les sédiments des trois sites présentent des compositions isotopiques du Pb fortement radiogéniques par rapports aux sédiments océaniques « classiques », que nous avons associées à une forte contribution de matériel issu de l’altération des cratons guyanais et brésilien dans la composante détritique. De plus, la décroissance radioactive de l’U dans les black shales du site 144 a généré des rapports 206-207Pb/204Pb extrêmement radiogéniques. Un mélange entre le manteau appauvri et les sédiments du site 543 reproduit les compositions isotopiques des laves de la partie nord de l’arc. Pour la partie sud de l’arc un mélange entre les sédiments les plus radiogéniques en Pb du site 144 et le manteau appauvri explique les compositions des laves des îles de la Martinique à Grenade. Une contribution croissante des black shales du nord vers le sud est nécessaire, et est de plus en accord avec l’augmentation du nord vers le sud de l’âge du plancher océanique subduit. Enfin, quelques sédiments de l’île de la Barbade présentent certaines caractéristiques compatibles avec leur implication dans la genèse des laves de la partie sud de l’arc.

The assemblage of ca. 6–4 Ma volcanic rocks exposed at the Sagehen Research station in the Truckee-Tahoe region of the northern Sierra Nevada, United States, is interpreted to be, within the Ancestral Cascades volcanic arc, a Lassen-type stratovolcano complex. Sagehen is of particular importance because it is one of the few Tertiary arc volcanic centres in California which has not been heavily glaciated during the Pleistocene. The volcanic rocks are variably porphyritic or aphanitic, including abundant plagioclase with clinopyroxene and amphibole. The rocks range from basalt to basaltic-andesite to andesite in composition. Basalts are olivineand clinopyroxene-bearing with minor phenocrysts of plagioclase. The basaltic-andesites are primarily pyroxene bearing while the andesites contain pyroxene-, plagioclase- and hornblende porphyritic phases. Sagehen arc lavas are calc-alkaline and enriched in the large ion lithophile elements and depleted in High Field Strength Elements. The basalts are depleted in Zr and Hf while the andesites are enriched with Zr and Hf relative to the middle rare earth elements. Compared to previously studied Ancestral Cascade arc samples, Sagehen region basalts have lower 143Nd/144Nd isotopic values that do not correspond to proposed mantle-lithosphere mixing lines, while the andesite samples appear to represent the interplay of these two components on a 87Sr/86Sr vs. 143Nd/144Nd. The trace element data and isotopic plots suggest that the melts that produced the basalts are from subduction modified mantle wedge peridotites that ponded near the base of the lithosphere similar to the generation of other subduction related calc-alkaline lavas along convergent continental margins. The andesitic samples appear to be the result of further modification through crustal assimilation as seen in the higher isotopic Sr contents in the andesites and Ce/Smpmn vs. Tb/Ybpmn plots. Finally, the proposed map units from Sylvester & Raines (2007) were found to contain various geochemical facies based on the samples collected indicating that some map units may have to be redefined or sub-divided.

Radionuclides are widely used in energy production and medical, military and industrial applications. Thus, understanding the behaviour of radionuclides which have been or may be released into ecosystems is important for human and environmental risk assessment. Modelling of radionuclides or their stable element analogues is the only tool that can predict the consequences of accidental release. In this thesis, two dynamic stochastic compartment models for radionuclide/element transfer in a marine coastal ecosystem and a freshwater lake were developed and implemented (Paper I and III), in order to model a hypothetical future release of multiple radionuclides from a nuclear waste disposal site. Element-specific mechanisms such as element uptake via diet and adsorption of elements to organic surfaces were connected to ecosystem carbon models. Element transport in two specific coastal and lake ecosystems were simulated for 26 and 13 elements, respectively (Papers I and III). Using the models, the concentration ratios (CR: the ratio of the element or radionuclide concentration in an organism to the concentration in water) were estimated for different groups of aquatic organisms. The coastal model was also compared with a 3D hydrodynamic spatial model (Paper II) for Cs, Ni and Th, and estimated confidence limits for their modelled CRs. In the absence of site-specific CR data, being able to estimate a range of CR values with such models is an alternative to relying on literature CR values that are not always relevant to the site of interest. Water chemistry was also found to influence uptake of contaminants by aquatic organisms. Empirical inverse relationships were derived between CRs of fish for stable Sr (CRSr) and Cs (CRCs) and water concentrations of their biochemical analogues Ca and K, respectively (Paper IV), illustrating how such relationships could be used in the prediction of more site-specific CRCs and CRSr in fish simply from water chemistry measurements. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

The Velay oriental (Massif Central, France) is a basaltic plateau with abundant viscous phonolite extrusions. The plateau lavas grade from alkali basalt to mugearite, but intermediate compositions are volumetrically scarce. Pyroclastics are absent. The most complete plateau sections are in the south, while in the north intermediate lavas appear only as viscous, phenocryst-rich extrusions. The plateau lavas were erupted between 11.7Ma and 7.6Ma, the southern phonolites 8.5Ma- 6.5Ma and new data show that the northern phonolites were erupted between 13.3Ma and 10.5Ma. Basement uplift occurred during the plateau-building stage, due to the emplacement of magma chambers. Intermediate lavas are scarce because they remained in the magma chambers due to their density, whereas phonolite was able to rise hydrostatically. The magma chambers were within 5km of the surface. Phonolites are divided into miaskitic and agpaiitic types on the basis of their chemistry and petrography. They evolved from the basalt by crystal settling in the magma chambers, whereas the aphyric plateau lavas evolved by plating crystals onto their conduit walls as they flowed towards the surface. Sr-isotopes show that the basalt-phonolite series is uncontaminated, whereas the northern intermediate lavas evolved by assimilation-fractional-crystallisation. A suite of cumulate nodules was recovered from a pyroclastic unit, which is probably younger than the Velay Miocene lavas. They are related to the northern intermediate lavas, and belong to the "Group II" class of nodules. Geothermobarometry suggests that both the cumulates and the northern intermediate lavas crystallised at a depth of 15-20km and probably became contaminated due to the smaller temperature difference between the geotherm and granite solidus at that depth. The vast majority of the Velay lavas are identical to alkalic ocean-island lavas, geochemically unaffected by their passage through the lithosphere, but with their relative proportions at the surface controlled by the density contrast between the basalt and basement granite.

Strontium isotope analysis has provided archaeologists with an unprecedented opportunity to study the mobility of humans and animals in the past. However, a lack of systematic environmental baseline data has seriously restricted the full potential of the analytical technique; there is little biosphere data available against which to compare measured skeletal data. This thesis examines the extent to which geographic variation in biosphere 87Sr/86Sr composition can be spatially resolved within the lowland terrain of England, in a geographically and geologically coherent study area. Systematically collected samples of vegetation, stream water and surface soils, including new and archived material have been used. The potential of these sample media to provide reliable estimates of the ⁸⁷Sr/⁸⁶Sr composition of bioavailable strontium are evaluated under both high-density and low-density sampling regimes, and against new analyses of local archaeological material. Areas lying south of the Anglian glacial limit, display a pattern of geographic ⁸⁷Sr/⁸⁶Sr biosphere variation (0.7080-0.7105) controlled by solid geology, as demonstrated by high-density biosphere mapping. Data collected at a wider geographic scale, including above superficial deposits, indicate the dominant influence of re-worked local rocks on the biosphere. These methods have enabled a reclassification of the archaeologically important Cretaceous Chalk domain. Analysis of rainwater and other indicators of atmospheric deposition show that, in this setting, local biosphere variation is not significantly perturbed by atmospheric inputs. Time-related data from archaeological cattle and sheep/goat tooth enamel suggest that the modern biosphere data can be used to understand livestock management regimes and that these are more powerful than using an average value from the enamel. A more complete understanding of possible patterns of mobility in a group of humans has been achieved through analysis of material from Winchester and comparison with the Chalk biosphere domain.

This diploma thesis deals with the nominal convergence and adoption of the single currency in Slovakia and Czech Republic. The first chapter briefly describes the formation of the Economic and Monetary Union. The second chapter concentrates on the Slovak and Czech Republic and their fulfilling of nominal convergent criteria. The third chapter describes and evaluates Slovak process of euro adoption. The forth chapter deals with the Czech Republic and euro and provides also opinion of various subjects on euro introduction.

The Gibraltar porphyry-Cu deposit is a large open pit porphyry Cu mine in Canada with the geological tonnage (production and reserves) of 3.2 Mt Cu. The Gibraltar deposit is hosted by the Granite Mountain Batholith (GMB), a tonalitic batholith with the surface exposure over 150 km2. All rocks within the batholith are tonalites with minor quartz diorites. The batholith intrudes into mafic volcanoclastic rocks of the Nicola group in the Quesnel terrane of the Canadian Cordillera. The Cu mineralization at Gibraltar is confined to a small 4.5 km2 area in the central part of the batholith and occurs primarily as disseminated chalcopyrite. New U-Pb dating on zircon shows protracted late Triassic magmatism spanning ~25 m.y. for the formation of the GMB. Early magmatism is dated at 229.2±4.4 Ma in unmineralized tonalites. Later, at least three magmatism form the Cu mineralization during a period spanning from 218.9±3.1 Ma to 205.8±2.1 Ma. These fertile magmas form in a more mature arc setting, superseded early barren magmatic activity in a more juvenile arc setting for the bulk of the GMB. Epidote in the GMB shows compositional zoning with Fe-poor cores and Fe-rich rims. The zoning in the mineralized intrusions likely reflects changes in hydrothermal fluid, from S-rich to S-poor. The data from the Gibraltar deposit shows that an economic porphyry Cu deposit may be found in igneous rocks with low Sr/Y in bulk rocks and low Eu/Eu* in zircon. In the Gibraltar deposit, Ce anomalies in zircon reflect oxidation conditions and are correlated with Cu resource associated with their respective intrusion.