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When DNA is sequenced, nucleotide calls are produced along with their individual error probabilities, which are usually reported in the form of a per-base quality score. However, these quality scores have not generally been incorporated into probabilistic models as there is typically a poor correlation between the predicted and observed error rates. Computational tools aimed at sequence analysis have therefore used arbitrary cutoffs on quality scores which often unnecessarily reduce the amount of data that can be analyzed. A different approach involves recalibration of those quality scores using known genomic variants to measure empirical error rates. However, for this heuristic to work, an adequate characterization of the variants present in a population must be available -which means that this approach is not possible for a wide range of species. This thesis develops methods to directly produce error probabilities that are representative of their empirical error rates for raw sequencing data. These can then be incorporated into Bayesian maximum a posteriori algorithms to make highly accurate inferences about the likelihood of the model that gave rise to this observed data. First, an algorithm to produce highly accurate nucleotide basecalls along with calibrated error probabilities is presented. Using the resulting data, individual reads can be robustly as- signed to their samples of origin and ancient DNA fragments can be inferred even at high error rates. For archaic hominin samples, the number of DNA fragments from present-day human contamination can also be accurately quantified. The novel algorithms developed during the course of this thesis provide an alternative approach to working with Illumina sequence data. They also provide a demonstrable improvement over existing computational methods for basecalling, inferring ancient DNA fragments, demultiplexing, and estimating present-day human contamination along with reconstruction of mitochondrial genomes in ancient hominins.

We study an energy functional able to describe low energy configurations of a two dimensional lattice with dislocations in a nonlinear elasticity regime. The main result can be described as follows: configurations of energy comparable to the lattice spacing consist of piecewise constant microrotations with small angle grain boundaries between them. Moreover, we also give bounds to the energy of particular configurations describing a small angle symmetric tilt grain boundary.

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This thesis studies the visualization of set collections either via or defines as the relations among contours. In the first part, dynamic Euler diagrams are used to communicate and improve semimanually the result of clustering methods which allow clusters to overlap arbitrarily. The contours of the Euler diagram are rendered as implicit surfaces called blobs in computer graphics. The interaction metaphor is the moving of items into or out of these blobs. The utility of the method is demonstrated on data arising from the analysis of gene expressions. The method works well for small datasets of up to one hundred items and few clusters. In the second part, these limitations are mitigated employing a GPU-based rendering of Euler diagrams and mixing textures and colors to resolve overlapping regions better. The GPU-based approach subdivides the screen into triangles on which it performs a contour interpolation, i.e. a fragment shader determines for each pixel which zones of an Euler diagram it belongs to. The rendering speed is thus increased to allow multiple hundred items. The method is applied to an example comparing different document clustering results. The contour tree compactly describes scalar field topology. From the viewpoint of graph drawing, it is a tree with attributes at vertices and optionally on edges. Standard tree drawing algorithms emphasize structural properties of the tree and neglect the attributes. Adapting popular graph drawing approaches to the problem of contour tree drawing it is found that they are unable to convey this information. Five aesthetic criteria for drawing contour trees are proposed and a novel algorithm for drawing contour trees in the plane that satisfies four of these criteria is presented. The implementation is fast and effective for contour tree sizes usually used in interactive systems and also produces readable pictures for larger trees. Dynamical models that explain the formation of spatial structures of RNA molecules have reached a complexity that requires novel visualization methods to analyze these model\''s validity. The fourth part of the thesis focuses on the visualization of so-called folding landscapes of a growing RNA molecule. Folding landscapes describe the energy of a molecule as a function of its spatial configuration; they are huge and high dimensional. Their most salient features are described by their so-called barrier tree -- a contour tree for discrete observation spaces. The changing folding landscapes of a growing RNA chain are visualized as an animation of the corresponding barrier tree sequence. The animation is created as an adaption of the foresight layout with tolerance algorithm for dynamic graph layout. The adaptation requires changes to the concept of supergraph and it layout. The thesis finishes with some thoughts on how these approaches can be combined and how the task the application should support can help inform the choice of visualization modality.

We investigate the truncated moment problem, especially the Carathéodory number, the set of atoms and determinacy.

Intensive Flächennutzung und Veränderungen von Klima und Standortbedingungen haben dazu geführt, dass mittlerweile 25 von 65 heimischen Heuschrecken-, Fangschrecken-, Schaben- und Ohrwurmarten als gefährdet oder ausgestorben gelten. Die Rote Liste enthält eine Artenliste und gibt einen Überblick über die Gefährdungssituation der einzelnen Arten. Bewertet werden Bestandssituation und der Bestandstrend.

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Introduction Capillarity describes the effects caused by the surface tension on liquids. When considering small amounts ofliquid,thesurfacetension becomes the dominating parameter. In this situation the arising mathematical task is to determine the occurring capillary surface. At the beginning of the research on this topic, problems such as the ascent of fluids in a circular tube, on a vertical wall or on a wedge were some of the first problems scientists were concerned with. At the beginning of the 19th century, scientists like Young1, Laplace2, Taylor 3 and Gauß 4 established the mathematical foundations of this field. For the capillary tube5 they found, by applying variational methods, the so called mean curvature equation or capillary equation with the associated boundary condition. As Finn in [Fin86, Chapter 1] describes, this leads to the following boundary value problem: divTu = u + in , · Tu = cos on @ where Tu = ∇u p 1 + |∇u|2 . is called the Lagrange6 multiplier and is the contact angle, established between the capillary surface and the container wall. In the past, one tried to solve the problem by linearisation – with more or less satisfying results. In the last decades, expedited by the developing of micromechanics and the arising space-technology, capillary effects became more and more significant. Thereby the observed results differed from the predicted. The reason is the strong non-linearity of the problem. Interior molecular forces are responsible for the establishing of equilibrium surfaces. The force, operating between two materials, is called adhesion and cohesion is the molecular force within a medium. Under some specifications there arises a non-negligible force, called disjoining pressure. This pressure causes an additional term in the capillary equation, which 1Thomas Young (*13 June 1773, Milverton; †10 May 1829, London); Englisch polymath; made notable contributions to the fields of vision, light, solid mechanics, energy, physiology, language, musical harmony and Egyptology, found the Young–Laplace equation 2Pierre-Simon (Marquis de) Laplace (28 March 1749, Beaumont-en-Auge; †5 March 1827, Paris); French mathematician and astronomer; found the Young–Laplace equation 3Brook Taylor (*18 August 1685, Edmonton; †29 December 1731, Somerset House/London); English mathematician; experiments in capillary attraction 4Johann Carl Friedlich Gauß (*30 April 1777, Braunschweig; †23 February 1855, G¨ottingen); German mathematician and scientist; contributed significantly to many fields, including number theory, statistics, analysis, differential geometry, geodesy, geophysics, electrostatics, astronomy and optics 5A capillary tube is a container with cross-section and perpendicular container walls, which contains an amount of liquid. 6Joseph-Louis de Lagrange (*25 January 1736, Turin; †10 April 1813, Paris); Italian mathematician and astronomer. 7 is called the disjoining pressure potential, denoted by P(x, u(x)). That is, we are led to the following modified capillary equation, see [MMS08]: divTu = u + P + in , with a similar boundary condition (see Section 1.3 for more details). The main task of this paper is to examine the behaviour of the capillary problem, considering the disturbance P. A generic example for such configurations is vapour nitrogen//liquid nitrogen//quartz, see also [Isr92, Chapter 11] or [MMS08]. The present work with regard to contents is divided in three parts. In the first part, inspired by the work of Concus and Finn [CF74], [FH89], we prove a Comparison Principle. As in the classical context, this principle is a powerful tool to find solutions of the boundary problem. Thus we can see that the disjoining pressure potential is the key for the asymptotic of the solutions. The second part is concerned with the asymptotic behaviour of the solutions for some classical cases. In particular for the capillary tube with circular cross-section (see [Mie93b], [Mie94], [Mie96] for the classical setting) the ascent on a horizontal wall and between two parallel horizontal plates, results are presented. There we are able to specify the asymptotic behaviour up to a constant term. In the last part we observe the solution of the problem on a corner. There it is more difficult to obtain a result. But in return, we gain a better result near the cusp of the edge. In the articles of Miersemann [Mie88], [Mie89], [Mie90] or Scholz [Sch04] some results for the classical setting are given. The formal arrangement is divided into three main chapters. The first of them is a summary of some notations which will be needed in the following chapters and also the physical background is illuminated. The main part, where asymptotic results are presented, is contained in Chapter 2. To afford a better reading, most of the proofs are given in Chapter 3.8

In the presented thesis we elaborated a general agent based model for multicellular populations. We used this model to shed light on the processes that determine the growth of avascular tumor spheroids and studied the key mechanisms of liver regeneration. In order to make such analyses possible, we developed a comprehensive software tool that allowed us to effectively simulate, visualize and analyze the constructed computational model. We started with a minimal model for two-dimensional monolayers which are a common experimental technique for in vitro cell cultures. We successively advanced our model in order to reflect an in vivo situation more closely for example by simulating complex three-dimensional tumor spheroids embedded in granular medium and host tissue. We proposed a biomechanical form of contact inhibition that was able to explain the experimentally observed linear growth of the diameter in monolayer cultures [Bru et al., 1998] [Bru et al., 2003] and their specific proliferation pattern where cells mainly proliferate at the monolayer border. Furthermore, our model could mimic the growth dynamics of monolayer cultures very precisely. Subsequently, we considered three-dimensional cell aggregates by studying substrate detachment whereby normally two-dimensional monolayers due to the failure of certain control mechanisms expand perpendicular to the monolayer plane. Failure of growth control mechanisms is known to play an important role in the development of cancer [Hanahan & Weinberg, 2000]. By additionally introducing nutrient diffusion and consumption, we established a further extended model for three-dimensional tumor spheroids which are a common experimental model in therapeutically oriented cancer research. Surprisingly, we found that the proposed biomechanical form of contact inhibition also explains the growth of these tumor spheroids. Thereby, our model suggests in agreement with experimental data [Freyer & Sutherland, 1985] [Freyer & Sutherland, 1986] that the nutrient concentration in the environment of a growing tumor, which is widely believed to control its growth, only determines the size of its necrotic core. Moreover, also in this three-dimensional situation our model precisely mimicked the growth dynamics and proliferation pattern of tumor spheroids in vitro where the necrotic core is enclosed by an intermediate layer of quiescent cells and an outer layer of proliferating cells [Kunz-Schughart, 1999]. We further advanced our model for the growth of three dimensional cell populations even closer towards in vivo tumors by including aspects from the surrounding tissue. We showed that the biomechanical properties of an embedding tissue have a major impact on the growth dynamics and morphology of growing cell populations by systematically varying the biophysical properties of the embedding tissue. Our model predicts Saffman-Taylor-like instabilities leading to fractal interfaces and an increased ability of cells to invade harsh environments if the motility of the embedding cells is small. We additionally observed large wavelength instabilities as a consequence of decreased density, increased elasticity, strong adhesion or 5. Summary 160 increased cell size of the embedding tissue or granular medium. Interestingly, we found a nearly complete inhibition of tumor growth for specific properties of the embedding tissue which, if experimentally validated, could have direct therapeutical implications. Furthermore, we achieved a remarkable agreement with experimental data on tumor growth dynamics by [Helmlinger et al., 1997] and [Galle et al., 2006]. However, the large variety of complex influences predicted by our model strongly indicates that the widespread experimental technique of embedding growing tumor spheroids in agarose gels [Helmlinger et al., 1997] [Galle et al., 2006] [Cheng et al., 2009] may not be sufficient to realistically capture all the biomechanical effects of an embedding tissue. Effects due to the granularity of the surrounding tissue, for example, are missing in experiments like those performed in [Helmlinger et al., 1997]. In contrast to chapter three where we mainly compared our model to published in vitro data, in chapter four we investigated a particular in vivo situation and studied the fascinating process of liver regeneration after intoxication with CCl4, a prototypical substance for drugs inducing pericentral liver damage. We established a procedure to use three-dimensional confocal laser scans to reconstruct in vivo tissues by image processing and image analysis. We then combined this very detailed and quantitative information with a further advanced version of our repeatedly experimentally validated model. We started with a minimal two-dimensional model for the regenerating liver lobule that nevertheless led to first impressions of the specific impact of the various factors that influence liver regeneration. On that basis we extended our model and created the first threedimensional agent-based model of the regenerating liver lobule. By capturing a 16 day regeneration process, our model underlined the importance of the complex columnar microarchitecture within the liver lobules, which is formed by hepatocytes and sinusoids. This microarchitecture ensures optimal exchange of metabolites between blood and hepatocytes. The model unambiguously predicted a so far unrecognized mechanism, the alignment of daughter hepatocytes along the orientation of the closest sinusoid, which we named hepatocyte-sinusoid alignment (HSA), as essential for liver regeneration. Only if HSA was included into the model the simulated tissue architecture was in agreement with the experimentally obtained data and no other likely mechanism could replace it. In order to experimentally validate the model prediction of HSA, we analyzed the orientation of daughter hepatocytes in relation to the sinusoids in three-dimensions. The results of this analysis clearly confirmed the model prediction and thus verified HSA as a yet unknown key mechanism of liver regeneration. During this analysis we introduced novel techniques that made currently experimentally not accessible information available by image processing and analysis of volumetric datasets obtained by confocal laser scanning microscopy. In addition to the three-dimensional analysis of HSA, we used a similar approach to obtain further currently not experimentally available information on the average 5. Summary 161 contact area between hepatocytes and sinusoids. Surprisingly, we found this parameter to allow for an automatic differentiation between normal liver tissue and hepatocellular carcinoma. The further pursuit of this finding will be interesting. In summary, in this thesis we present an interdisciplinary approach to combine microscopic imaging, image processing and analysis and computational modeling - all in three dimensions. The integration of methods and results from different scientific fields like cell biology, physics and computer science enabled us to obtain new insights in cancer research and hepatology. We therefore consider the presented interdisciplinary approach and the corresponding procedures exemplary and widely applicable in the systems biology of tissues in general.