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The locality of Zwartbas is situated at the border of Namibia and South Africa about 15 km west of Noordoewer. The mapped area is confined by the Tandjieskoppe Mountains in the north and the Orange River in the south. Outcropping rocks are predominantly sediments of the Nama Group and of the Karoo Supergroup. During the compilation of this paper doubts arose about the correct classification of the Nama rocks as it is found in literature. Since no certain clues were found to revise the classification of the Nama rocks, the original classification remains still valid. Thus the Kuibis and Schwarzrand Subgroup constitute the Nama succession and date it to Vendian age. A glacial unconformity represents a hiatus for about 260 Ma. This is covered by sediments of the Karoo Supergroup. Late Carboniferous and early Permian glacial deposits of diamictitic shale of the Dwyka and shales of the Ecca Group overlie the unconformity. The shales of the Dwyka Group contain fossiliferous units and volcanic ash-layers. A sill of the Jurassic Tandjiesberg Dolerite Complex (also Karoo Supergroup) intruded rocks at the Dwyka-Ecca-boundary. Finally fluvial and aeolian deposits and calcretes of the Cretaceous to Tertiary Kalahari Group and recent depositionary events cover the older rocks occasionally.
According to the “canonical” paradigm of GPCR signaling, agonist-bound GPCRs only signal to the downstream adenylyl cyclase enzyme when they are seated at the plasma membrane. Upon prolonged binding of an agonist, receptor internalization usually takes place, leading to the termination of this downstream signaling pathway and activation of alternative ones. However, a set of recent studies have shown that at least some GPCRs (e.g. thyroid stimulating hormone receptor) continue signaling to adenylyl cyclase after internalization. In this study, I aimed to investigate canonical signaling by internalized μ opioid receptors (MORs), which are Gi-coupled receptors, using a fluorescence resonance energy transfer (FRET) sensor for cyclic AMP (cAMP) known as Epac1-camps. My results show that the cyclic AMP inhibition signal induced by the binding of DAMGO, a MOR agonist, persists after agonist washout. We hypothesized that this persistent signal might come from internalized DAMGO-bound receptors located in the endosomal compartment. To test this hypothesis, I used dynasore and Dyngo 4a, two dynamin inhibitors that are known to prevent clathrin-mediated endocytosis. Interestingly, dynasore but not Dyngo 4a pretreatment largely blunted the response to MOR activation as well as to adenylyl cyclase activation with Forskolin (FSK). In addition, DAMGO-induced cAMP signal remained persistent even in the presence of 30 M Dyngo 4a. These results might point to a complex interplay between clathrin-mediated internalization and MOR signaling. Further experiments are required to elucidate the mechanisms underlying the persistent MOR signaling and to fully clarify whether MORs are capable of Gi signaling in the endosomal compartment.
The scope of this work is to develop a novel single-molecule imaging technique by combining atomic force microscopy (AFM) and optical fluorescence microscopy. The technique is used for characterizing the structural properties of multi-protein complexes. The high-resolution fluorescence microscopy and AFM are combined (FIONA-AFM) to allow for the identification of individual proteins in such complexes. This is achieved by labeling single proteins with fluorescent dyes and determining the positions of these fluorophores with high precision in an optical image. The same area of the sample is subsequently scanned by AFM. Finally, the two images are aligned and the positions of the fluorophores are displayed on top of the topographical data. Using quantum dots as fiducial markers in addition to fluorescently labeled proteins, fluorescence and AFM information can be aligned with an accuracy better than 10 nm, which is sufficient to identify single fluorescently labeled proteins in most multi-protein complexes. The limitations of localization precision and accuracy in fluorescence and AFM images are investigated, including their effects on the overall registration accuracy of FIONA-AFM hybrid images. This combination of the two complementary techniques opens a wide spectrum of possible applications to the study of protein interactions, because AFM can yield high resolution (5–10 nm) information about the conformational properties of multi-protein complexes while the fluorescence can indicate spatial relationships of the proteins within the complexes. Additionally, computer simulations are performed in order to validate the accuracy of the registration algorithm.
This thesis gives an overview over mathematical modeling of complex fluids with the discussion of underlying mechanical principles, the introduction of the energetic variational framework, and examples and applications. The purpose is to present a formal energetic variational treatment of energies corresponding to the models of physical phenomena and to derive PDEs for the complex fluid systems. The advantages of this approach over force-based modeling are, e.g., that for complex systems energy terms can be established in a relatively easy way, that force components within a system are not counted twice, and that this approach can naturally combine effects on different scales. We follow a lecture of Professor Dr. Chun Liu from Penn State University, USA, on complex fluids which he gave at the University of Wuerzburg during his Giovanni Prodi professorship in summer 2012. We elaborate on this lecture and consider also parts of his work and publications, and substantially extend the lecture by own calculations and arguments (for papers including an overview over the energetic variational treatment see [HKL10], [Liu11] and references therein).
From the introduction: It is not always easy to define what a word means. We can choose between a variety of possibilities, from simply pointing at the correct object as we say its name to lengthy definitions in encyclopaedias, which can sometimes fill multiple pages. Although the former approach is pretty straightforward and is also very important for first language acquisition, it is obviously not a practical solution for defining the semantics of the whole lexicon. The latter approach is more widely accepted in this context, but it turns out that defining dictionary and encyclopaedia entries is not an easy task. In order to simplify the challenge of defining the meaning of words, it is of great advantage to organize the lexicon in a way that the structure in which the words are integrated gives us information about the meaning of the words by showing their relation to other words. These semantic relations are the focal point of this paper. In the first chapter, different ways to describe meaning will be discussed. It will become obvious why semantic relations are a very good instrument to organizing the lexicon. The second chapter deals with WordNet, an electronic lexical database which follows precisely this approach. We will examine the semantic relations which are used in WordNet and we will study the distinct characteristics of each of them. Furthermore, we will see which contribution is made by which relation to the organization of the lexicon. Finally, we will look at the downside of the fact that WordNet is a manually engineered network by examining the shortcomings of WordNet. In the third chapter, an alternative approach to linguistics is introduced. We will discuss the principles of corpus linguistics and, using the example of the British National Corpus, we will consider possibilities to extract semantic relations from language corpora which could help to overcome the deficiencies of the knowledge based approach. In the fourth chapter, I will describe a project the goal of which is to extend WordNet by findings from cognitive linguistics. Therefore, I will discuss the development process of a piece of software that has been programmed in the course of this thesis. Furthermore, the results from a small‐scale study using this software will be analysed and evaluated in order to check for the success of the project.