Scaling Laws and Similarity Detection in Sequence Alignment with Gaps

We study the problem of similarity detection by sequence alignment with gaps, using a recently established theoretical framework based on the morphology of alignment paths. Alignments of sequences without mutual correlations are found to have scale-invariant statistics. This is the basis for a scaling theory of alignments of correlated sequences. Using a simple Markov model of evolution, we generate sequences with well-defined mutual correlations and quantify the fidelity of an alignment in an unambiguous way. The scaling theory predicts the dependence of the fidelity on the alignment parameters and on the statistical evolution parameters characterizing the sequence correlations. Specific criteria for the optimal choice of alignment parameters emerge from this theory. The results are verified by extensive numerical simulations.Comment: 25 pages, 11 figure

A cell-based simulation software for multi-cellular systems

CellSys is a modular software tool for efficient off-lattice simulation of growth and organization processes in multi-cellular systems in 2D and 3D. It implements an agent-based model that approximates cells as isotropic, elastic and adhesive objects. Cell migration is modeled by an equation of motion for each cell. The software includes many modules specifically tailored to support the simulation and analysis of virtual tissues including real-time 3D visualization and VRML 2.0 support. All cell and environment parameters can be independently varied which facilitates species specific simulations and allows for detailed analyses of growth dynamics and links between cellular and multi-cellular phenotypes

Modeling the Effect of Deregulated Proliferation and Apoptosis on the Growth Dynamics of Epithelial Cell Populations In Vitro

AbstractWe present a three-dimensional individual cell-based, biophysical model to study the effect of normal and malfunctioning growth regulation and control on the spatial-temporal organization of growing cell populations in vitro. The model includes explicit representations of typical epithelial cell growth regulation and control mechanisms, namely 1), a cell-cell contact-mediated form of growth inhibition; 2), a cell-substrate contact-dependent cell-cycle arrest; and 3), a cell-substrate contact-dependent programmed cell death (anoikis). The model cells are characterized by experimentally accessible biomechanical and cell-biological parameters. First, we study by variation of these cell-specific parameters which of them affect the macroscopic morphology and growth kinetics of a cell population within the initial expanding phase. Second, we apply selective knockouts of growth regulation and control mechanisms to investigate how the different mechanisms collectively act together. Thereby our simulation studies cover the growth behavior of epithelial cell populations ranging from undifferentiated stem cell populations via transformed variants up to tumor cell lines in vitro. We find that the cell-specific parameters, and in particular the strength of the cell-substrate anchorage, have a significant impact on the population morphology. Furthermore, they control the efficacy of the growth regulation and control mechanisms, and consequently tune the transition from controlled to uncontrolled growth that is induced by the failures of these mechanisms. Interestingly, however, we find the qualitative and quantitative growth kinetics to be remarkably robust against variations of cell-specific parameters. We compare our simulation results with experimental findings on a number of epithelial and tumor cell populations and suggest in vitro experiments to test our model predictions

Guided interactive image segmentation using machine learning and color based data set clustering

We present a novel approach that combines machine learning based interactive image segmentation using supervoxels with a clustering method for the automated identification of similarly colored images in large data sets which enables a guided reuse of classifiers. Our approach solves the problem of significant color variability prevalent and often unavoidable in biological and medical images which typically leads to deteriorated segmentation and quantification accuracy thereby greatly reducing the necessary training effort. This increase in efficiency facilitates the quantification of much larger numbers of images thereby enabling interactive image analysis for recent new technological advances in high-throughput imaging. The presented methods are applicable for almost any image type and represent a useful tool for image analysis tasks in general

Der Mensch im Raum : über verschiedene Verständnisse von Raum in Planung und Sozialwissenschaften und theoretische Ansätze zu Mensch-Raum-Beziehungen

Eine der zentralen Aufgaben der Planer ist, Raum in Hinblick auf die Bedürfnisse von Menschen zu gestalten. Damit wird in der Regel die physisch-materielle Dimension von Raum assoziiert. Doch Planer beeinflussen mit ihrem Tun auch die Gesellschaft und einzelne Menschen, also die soziale und individuelle Dimension. Daher ist es für viele Planer interessant, wie Menschen mit Raum in Verbindung stehen. Theoretisches Wissen hierzu ist vorwiegend in sozialwissenschaftlichen Disziplinen zu finden. Die Verteilung des Wissens und die fehlende einheitliche Theoriebasis erschweren es Fachfremden, wie Planern, einen Überblick zu gewinnen und einen für die jeweilige Aufgabenstellung passenden Ansatz herauszufiltern. Zudem wird der Begriff „Raum“ in den Sozialwissenschaften meist anders verstanden, als es unter Planern üblich ist. Diese Arbeit liefert die Grundlage für einen verbesserten interdisziplinären Austausch zwischen Sozialwissenschaftlern und Planern auf Basis klarerer Begriffsdefinitionen. Im ersten Teil der Arbeit werden unterschiedliche Verständnisse des Begriffes Raum aus Planungswissenschaften und Sozialwissenschaften analysiert. Das Ziel dieses Kapitel ist es, einen Überblick über gängige Raumbegriffe zu schaffen, der als Grundlage für einen interdisziplinären Austausch genutzt werden kann. In einem zweiten Teil werden theoretische Ansätze aus den Sozialwissenschaften zur Interaktion von Menschen und Raum aufgearbeitet und analysiert. Das Ziel dieses Kapitels ist es, einen Überblick über gängige Ansätze zu liefern und ihre Möglichkeiten und Grenzen zu erläutern. In einem dritten Teil wird versucht, die Erkenntnisse der beiden Theorieteile zu Raumbegriffen und Ansätzen über Interaktionen von Mensch und Raum zusammenzuführen. Hieran anschließend wird ein Exkurs geführt, in dem weiterführende Erkenntnisse zu Mensch-Raum-Beziehungen, meist aus empirischen Studien, umrissen werden. Insgesamt wird ein Überblick über verschiedene Definitionen von Raum und über unterschiedliche theoretische Ansätze zu Interaktionen zwischen Mensch und Raum geschaffen

Potential of wind turbines to elicit seizures under various meteorological conditions

Purpose: To determine the potential risk of epileptic seizures from wind turbine shadow flicker under various meteorologic conditions. Methods: We extend a previous model to include attenuation of sunlight by the atmosphere using the libradtran radiative transfer code. Results: Under conditions in which observers look toward the horizon with their eyes open we find that there is risk when the observer is closer than 1.2 times the total turbine height when on land, and 2.8 times the total turbine height in marine environments, the risk limited by the size of the image of the sun's disc on the retina. When looking at the ground, where the shadow of the blade is cast, observers are at risk only when at a distance <36 times the blade width, the risk limited by image contrast. If the observer views the horizon and closes their eyes, however, the stimulus size and contrast ratio are epileptogenic for solar elevation angles down to approximately 5°. Discussion: Large turbines rotate at a rate below that at which the flicker is likely to present a risk, although there is a risk from smaller turbines that interrupt sunlight more than three times per second. For the scenarios considered, we find the risk is negligible at a distance more than about nine times the maximum height reached by the turbine blade, a distance similar to that in guidance from the United Kingdom planning authorities. © 2009 International League Against Epilepsy

Individual fates of mesenchymal stem cells in vitro

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>cultivated stem cell populations are in general heterogeneous with respect to their expression of differentiation markers. In hematopoietic progenitor populations, this heterogeneity has been shown to regenerate within days from isolated subpopulations defined by high or low marker expression. This kind of plasticity has been suggested to be a fundamental feature of mesenchymal stem cells (MSCs) as well. Here, we study MSC plasticity on the level of individual cells applying a multi-scale computer model that is based on the concept of noise-driven stem cell differentiation.</p> <p>Results</p> <p>By simulation studies, we provide detailed insight into the kinetics of MSC organisation. Monitoring the fates of individual cells in high and low oxygen culture, we calculated the average transition times of individual cells into stem cell and differentiated states. We predict that at low oxygen the heterogeneity of a MSC population with respect to differentiation regenerates from any selected subpopulation in about two days. At high oxygen, regeneration becomes substantially slowed down. Simulation results on the composition of the functional stem cell pool of MSC populations suggest that most of the cells that constitute this pool originate from more differentiated cells.</p> <p>Conclusions</p> <p>Individual cell-based models are well-suited to provide quantitative predictions on essential features of the spatio-temporal organisation of MSC <it>in vitro</it>. Our predictions on MSC plasticity and its dependence on the environment motivate a number of <it>in vitro </it>experiments for validation. They may contribute to a better understanding of MSC organisation <it>in vitro</it>, including features of clonal expansion, environmental adaptation and stem cell ageing.</p

Emergence of regulatory networks in simulated evolutionary processes

Despite spectacular progress in biophysics, molecular biology and biochemistry our ability to predict the dynamic behavior of multicellular systems under different conditions is very limited. An important reason for this is that still not enough is known about how cells change their physical and biological properties by genetic or metabolic regulation, and which of these changes affect the cell behavior. For this reason, it is difficult to predict the system behavior of multicellular systems in case the cell behavior changes, for example, as a consequence of regulation or differentiation. The rules that underlie the regulation processes have been determined on the time scale of evolution, by selection on the phenotypic level of cells or cell populations. We illustrate by detailed computer simulations in a multi-scale approach how cell behavior controlled by regulatory networks may emerge as a consequence of an evolutionary process, if either the cells, or populations of cells are subject to selection on particular features. We consider two examples, migration strategies of single cells searching a signal source, or aggregation of two or more cells within minimal multiscale models of biological evolution. Both can be found for example in the life cycle of the slime mold Dictyostelium discoideum. However, phenotypic changes that can lead to completely different modes of migration have also been observed in cells of multi-cellular organisms, for example, as a consequence of a specialization in stem cells or the de-differentiation in tumor cells. The regulatory networks are represented by Boolean networks and encoded by binary strings. The latter may be considered as encoding the genetic information (the genotype) and are subject to mutations and crossovers. The cell behavior reflects the phenotype. We find that cells adopt naturally observed migration strategies, controlled by networks that show robustness and redundancy. The model simplicity allow us to unambiguously analyze the regulatory networks and the resulting phenotypes by different measures and by knockouts of regulatory elements. We illustrate that in order to maintain a cells' phenotype in case of a knockout, the cell may have to be able to deal with contradictory information. In summary, both the cell phenotype as well as the emerged regulatory network behave as their biological counterparts observed in nature

Modeling the impact of granular embedding media, and pulling versus pushing cells on growing cell clones

International audienceIn this paper, we explore how potential biomechanical influences on cell cycle entrance and cell migration affect the growth dynamics of cell populations. We consider cell populations growing in free, granular and tissuelike environments using a mathematical single-cell-based model. In a free environment we study the effect of pushing movements triggered by proliferation versus active pulling movements of cells stretching cell-cell contacts on the multi-cellular kinetics and the cell population morphotype. By growing cell clones embedded in agarose gel or cells of another type, one can mimic aspects of embedding tissues. We perform simulation studies of cell clones expanding in an environment of granular objects and of chemically inert cells. In certain parameter ranges, we find the formation of invasive fingers reminiscent of viscous fingering. Since the simulation studies are highly computation-time consuming, we mainly study one-cell-thick monolayers and show that for selected parameter settings the results also hold for multi-cellular spheroids. Finally, we compare our model to the experimentally observed growth dynamics of multi-cellular spheroids in agarose gel