Graben width controlling syn-rift sedimentation: the Palaeogene southern Upper Rhine Graben as an example

Eocene to Early Oligocene syn-rift deposits of the southern Upper Rhine Graben (URG) accumulated in restricted environments. Sedimentation was controlled by local clastic supply from the graben flanks, as well as by strong intra-basinal variations in accommodation space due to differential tectonic subsidence, that in turn led to pronounced lateral variations in depositional environment. Three large-scale cycles of intensified evaporite sedimentation were interrupted by temporary changes towards brackish or freshwater conditions. They form three major base level cycles that can be traced throughout the basin, each of them representing a stratigraphic sub-unit. A relatively constant amount of horizontal extension (ΔL) in the range of 4-5km has been estimated for the URG from numerous cross-sections. The width of the rift (L f ), however, varies between 35 and more than 60km, resulting in a variable crustal stretching factor between the bounding masterfaults. Apart from block tilting, tectonic subsidence was, therefore, largely controlled by changes in the initial rift width (L 0). The along-strike variations of the graben width are responsible for the development of a deep, trough-like evaporite basin (Potash Basin) in the narrowest part of the southern URG, adjacent to shallow areas in the wider parts of the rift such as the Colmar Swell in the north and the Rhine Bresse Transfer Zone that delimits the URG to the south. Under a constant amount of extension, the along-strike variation in rift width is the principal factor controlling depo-centre development in extensional basin

Analyse der Funktionen der A Disintegrin und Metalloprotease 10 (ADAM10) in Leber und Niere und der Regulation der Proteaseaktivität

Die A Disintegrin und Metalloprotease 10 (ADAM10) gewährleistet über die Proteolyse seiner Substrate die zelluläre Funktionalität. Insbesondere die ADAM10-abhängige Aktivierung des Notch-Signalweges stellt einen wichtigen Schalter für Entwicklungsprozesse dar. Durch die Verwendung verschiedener Gewebs-spezifischer Knockout-Mausmodelle für ADAM10 wurde die Rolle der Protease untersucht. Ein ADAM10-Knockout in den Podozyten der Niere hatte keinen unmittelbaren Einfluss auf die Entwicklung und Funktion dieser Zellen. In einem anti-Podozyten-Antikörper-basierten Nephritis-Modell konnte gezeigt werden, dass der podozytäre Verlust von ADAM10 den Krankheitsverlauf verzögert. Ähnlich wie in den Mäusen führte die Antikörper-Behandlung auch im Podozyten-Zellmodell zu einer Schädigung der Zellen, die unabhängig vom Notch-Signalweg erfolgte. Diese Experimente belegten eine verringerte Zell-Zell-Interaktion durch eine ADAM10-vermittelte Proteolyse von Cadherinen, die im Tiermodell möglicherweise zum Verlust der Integrität der Schlitzmembran im Rahmen der Nephritis beiträgt. ADAM10 erscheint daher als ein wichtiger Mediator der Schädigung der Schlitzmembran während der Entwicklung einer Nephritis. Mäuse mit einer ADAM10-Defizienz in Hepatoblasten, Hepatozyten und Cholangiozyten wiesen Nekrosen des Leberparenchyms auf, die aus einem gestörten Galleabfluss aus der Leber resultierten. Die Notch2-abhängige Entwicklung der Gallengänge war jedoch unauffällig. Stattdessen wurde eine reduzierte Transkription und Expression von Gallensäuretransportern als Ursache der Nekrosen identifiziert. Während der Regeneration der nekrotischen Areale terminierte ADAM10 die Proliferation von Lebervorläuferzellen (LPC) über die Hemmung des HGF/cMet-Signalweges. Die Daten identifizieren ADAM10 als essentiellen Faktor der Leberhomöostase. In der vorliegenden Arbeit wurden zudem die ADAM10-Interaktoren FK506-bindendes Protein 38 (FKBP38) und TGF-β-aktivierte Kinase 1 (TAK1, MAP3K7) untersucht [...]The A Disintegrin And Metalloprotease 10 (ADAM10) ensures cellular functionality through the proteolysis of integral membrane or GPI-anchored proteins. In this regard the ADAM10-dependent activation of the Notch pathway marks an essential switch in developmental processes. Due to its diverse molecular functions, the role of the protease ADAM10 was investigated using different tissue-specific knockout mice. ADAM10 deficiency in podocytes of the kidney did not affect the development or the function of these cells. An anti-podocyte antibody-based nephritis model revealed that the loss of ADAM10 delays the progression of the disease. In line with this observation an antibody-treated podocyte cell line also showed signs of cell damage, which was independent of Notch signalling. The cell-based experiments demonstrated that an ADAM10-dependent proteolysis of cadherins caused an impaired cell-cell interaction, possibly explaining the loss of slit diaphragm integrity in the animal model. The study suggests that ADAM10 is an important mediator of slit diaphragm damage during the development of a nephritis. Mice deficient for ADAM10 in hepatoblasts, hepatocytes and cholangiocytes displayed necrosis in liver parenchyma due to a disturbed bile flow. The Notch2-dependent development of the bile ducts appeared normal. Liver necrosis was caused by a reduced transcription and expression of bile acid transporters. During the regeneration of necrotic areas ADAM10 controlled the proliferation of liver progenitor cells (LPC) through inhibition of the HGF/cMet-pathway. The data indicate that ADAM10 acts as an important regulator of liver tissue homeostasis. In cell-based experiments, the ADAM10 interacting proteins FK506 binding protein 38 (FKBP38) and TGF-β activated kinase 1 (TAK1, MAP3K7) were analysed. While FKBP38 regulated the cellular transport of ADAM10, MAP3K7 blocked Adam10 transcription. Additionally, the kinase specifically affected ADAM10-dependent APP proteolysis

Analyse der Funktionen der A Disintegrin und Metalloprotease 10 (ADAM10) in Leber und Niere und der Regulation der Proteaseaktivität

Die A Disintegrin und Metalloprotease 10 (ADAM10) gewährleistet über die Proteolyse seiner Substrate die zelluläre Funktionalität. Insbesondere die ADAM10-abhängige Aktivierung des Notch-Signalweges stellt einen wichtigen Schalter für Entwicklungsprozesse dar. Durch die Verwendung verschiedener Gewebs-spezifischer Knockout-Mausmodelle für ADAM10 wurde die Rolle der Protease untersucht. Ein ADAM10-Knockout in den Podozyten der Niere hatte keinen unmittelbaren Einfluss auf die Entwicklung und Funktion dieser Zellen. In einem anti-Podozyten-Antikörper-basierten Nephritis-Modell konnte gezeigt werden, dass der podozytäre Verlust von ADAM10 den Krankheitsverlauf verzögert. Ähnlich wie in den Mäusen führte die Antikörper-Behandlung auch im Podozyten-Zellmodell zu einer Schädigung der Zellen, die unabhängig vom Notch-Signalweg erfolgte. Diese Experimente belegten eine verringerte Zell-Zell-Interaktion durch eine ADAM10-vermittelte Proteolyse von Cadherinen, die im Tiermodell möglicherweise zum Verlust der Integrität der Schlitzmembran im Rahmen der Nephritis beiträgt. ADAM10 erscheint daher als ein wichtiger Mediator der Schädigung der Schlitzmembran während der Entwicklung einer Nephritis. Mäuse mit einer ADAM10-Defizienz in Hepatoblasten, Hepatozyten und Cholangiozyten wiesen Nekrosen des Leberparenchyms auf, die aus einem gestörten Galleabfluss aus der Leber resultierten. Die Notch2-abhängige Entwicklung der Gallengänge war jedoch unauffällig. Stattdessen wurde eine reduzierte Transkription und Expression von Gallensäuretransportern als Ursache der Nekrosen identifiziert. Während der Regeneration der nekrotischen Areale terminierte ADAM10 die Proliferation von Lebervorläuferzellen (LPC) über die Hemmung des HGF/cMet-Signalweges. Die Daten identifizieren ADAM10 als essentiellen Faktor der Leberhomöostase. In der vorliegenden Arbeit wurden zudem die ADAM10-Interaktoren FK506-bindendes Protein 38 (FKBP38) und TGF-β-aktivierte Kinase 1 (TAK1, MAP3K7) untersucht [...]The A Disintegrin And Metalloprotease 10 (ADAM10) ensures cellular functionality through the proteolysis of integral membrane or GPI-anchored proteins. In this regard the ADAM10-dependent activation of the Notch pathway marks an essential switch in developmental processes. Due to its diverse molecular functions, the role of the protease ADAM10 was investigated using different tissue-specific knockout mice. ADAM10 deficiency in podocytes of the kidney did not affect the development or the function of these cells. An anti-podocyte antibody-based nephritis model revealed that the loss of ADAM10 delays the progression of the disease. In line with this observation an antibody-treated podocyte cell line also showed signs of cell damage, which was independent of Notch signalling. The cell-based experiments demonstrated that an ADAM10-dependent proteolysis of cadherins caused an impaired cell-cell interaction, possibly explaining the loss of slit diaphragm integrity in the animal model. The study suggests that ADAM10 is an important mediator of slit diaphragm damage during the development of a nephritis. Mice deficient for ADAM10 in hepatoblasts, hepatocytes and cholangiocytes displayed necrosis in liver parenchyma due to a disturbed bile flow. The Notch2-dependent development of the bile ducts appeared normal. Liver necrosis was caused by a reduced transcription and expression of bile acid transporters. During the regeneration of necrotic areas ADAM10 controlled the proliferation of liver progenitor cells (LPC) through inhibition of the HGF/cMet-pathway. The data indicate that ADAM10 acts as an important regulator of liver tissue homeostasis. In cell-based experiments, the ADAM10 interacting proteins FK506 binding protein 38 (FKBP38) and TGF-β activated kinase 1 (TAK1, MAP3K7) were analysed. While FKBP38 regulated the cellular transport of ADAM10, MAP3K7 blocked Adam10 transcription. Additionally, the kinase specifically affected ADAM10-dependent APP proteolysis

Twin Neural Network Regression is a Semi-Supervised Regression Algorithm

Twin neural network regression (TNNR) is a semi-supervised regression algorithm, it can be trained on unlabelled data points as long as other, labelled anchor data points, are present. TNNR is trained to predict differences between the target values of two different data points rather than the targets themselves. By ensembling predicted differences between the targets of an unseen data point and all training data points, it is possible to obtain a very accurate prediction for the original regression problem. Since any loop of predicted differences should sum to zero, loops can be supplied to the training data, even if the data points themselves within loops are unlabelled. Semi-supervised training improves TNNR performance, which is already state of the art, significantly

Exploring Phase Diagrams with Functional Renormalization and Artificial Neural Networks: From the Hubbard Model to Lattice Gauge Theory

This thesis is dedicated to provide physicists with new and improved techniques to examine phase diagrams and phase transitions. One the one hand, an analysis of the effects of different regularization schemes in functional renormalization group calculations is provided. Building on this knowledge, an investigation of the phase diagram of the Hubbard-Model on the square lattice is performed using the functional renormalization group. The calculation reveals leading instabilities in the d-wave superconducting and different antiferromagnetic channels. In the symmetry broken phases there are a changing Fermi surface geometry, coexistence phases of d-wave superconductivity and antiferromagnetism as well as a mutual tendency of superconductivity and antiferromagnetism to repel each other. On the other hand, a scheme to discover phase transitions using unsupervised artifcial neural networks is developed. Further, a method to interpret artifcial neural networks is introduced. These methods are applied to systems ranging from the two dimensional Ising Model to four dimensional SU(2) lattice gauge theory. They find the existence of different phases, calculate phase boundaries and derive the explicit formulas of the quantities by which the neural network distinguishes between phases. It turns out that these quantities are order parameters and other thermodynamic quantities

Experimental Investigation on Heat Transfer Enhancement with Passive Inserts in Flat Tubes in due Consideration of an Efficiency Assessment

This paper presents results of an experimental investigation on pressure drop and heat transfer for a wide range of Reynolds and Prandtl numbers ranging from 8 < Pr < 60 and 40 < Re < 3500, for flat tubes without and with passive inserts. For three different kinds of passive insert designs, the impact on heat and momentum transfer due to coaction of the total set of passive inserts with different shape and amount was investigated. Experimental results were analyzed regarding two main aspects: Heat transfer mechanisms and pressure drop induced by friction and form drag forces due to the presence of different shapes. After heat and momentum transfer mechanisms for each passive insert design were analyzed, heat transfer and pressure drop enhancement were compared to each other, leading to an efficiency discussion. Different concepts for efficiency evaluation, which are cited in literature, were applied to the presented experimental data. Pros and cons of the different concepts are discussed. Finally, we propose an equation for evaluation of total performance, which fully respects the energetic and exergetic aspects of heat transfer and pressure drop enhancement