Waterpixels

International audience— Many approaches for image segmentation rely on a 1 first low-level segmentation step, where an image is partitioned 2 into homogeneous regions with enforced regularity and adherence 3 to object boundaries. Methods to generate these superpixels have 4 gained substantial interest in the last few years, but only a few 5 have made it into applications in practice, in particular because 6 the requirements on the processing time are essential but are not 7 met by most of them. Here, we propose waterpixels as a general 8 strategy for generating superpixels which relies on the marker 9 controlled watershed transformation. We introduce a spatially 10 regularized gradient to achieve a tunable tradeoff between the 11 superpixel regularity and the adherence to object boundaries. 12 The complexity of the resulting methods is linear with respect 13 to the number of image pixels. We quantitatively evaluate our 14 approach on the Berkeley segmentation database and compare 15 it against the state-of-the-art

Construction of boundary element models in bioelectromagnetism

Multisensor electro- and magnetoencephalographic (EEG and MEG) as well as electro- and magnetocardiographic (ECG and MCG) recordings have been proved useful in noninvasively extracting information on bioelectric excitation. The anatomy of the patient needs to be taken into account, when excitation sites are localized by solving the inverse problem. In this work, a methodology has been developed to construct patient specific boundary element models for bioelectromagnetic inverse problems from magnetic resonance (MR) data volumes as well as from two orthogonal X-ray projections. The process consists of three main steps: reconstruction of 3-D geometry, triangulation of reconstructed geometry, and registration of the model with a bioelectromagnetic measurement system. The 3-D geometry is reconstructed from MR data by matching a 3-D deformable boundary element template to images. The deformation is accomplished as an energy minimization process consisting of image and model based terms. The robustness of the matching is improved by multi-resolution and global-to-local approaches as well as using oriented distance maps. A boundary element template is also used when 3-D geometry is reconstructed from X-ray projections. The deformation is first accomplished in 2-D for the contours of simulated, built from the template, and real X-ray projections. The produced 2-D vector field is back-projected and interpolated on the 3-D template surface. A marching cube triangulation is computed for the reconstructed 3-D geometry. Thereafter, a non-iterative mesh-simplification method is applied. The method is based on the Voronoi-Delaunay duality on a 3-D surface with discrete distance measures. Finally, the triangulated surfaces are registered with a bioelectromagnetic measurement utilizing markers. More than fifty boundary element models have been successfully constructed from MR images using the methods developed in this work. A simulation demonstrated the feasibility of X-ray reconstruction; some practical problems of X-ray imaging need to be solved to begin tests with real data.reviewe

Jamming and Unjamming in Cancer Cells

Jamming' ist ein faszinierender, nicht vollständig verstandener Prozess in der Physik der weichen Materie. Zelluläres Jamming' tritt auch in biologischem Gewebe auf und muss sich im Fall von Krebszellen im Tumorgewebe aufgrund der dichten Packung der Zellen über der dichtesten Kugelpackung anders verhalten als die bekannten 'Jamming' Systeme. In meiner Dissertation skizziere ich wesentliche Ergebnisse zum Verständnis dieses neuen physikalischen Phänomens. Meine Erkenntnisse tragen dazu bei die Dichotomie zwischen den Theorien der dichteinduzierten und der forminduzierten 'Zelljamming' aufzulösen. Die gewonnenen Erkenntnisse weisen auf die Möglichkeit hin Krebszellformen und deren Zellkernformen als Tumormarker für die Metastasierung zu verwenden. Ich fand ein kritisches Skalierungsverhalten für die Dynamik der Neuanordnung von Zellen in der Nähe des Jamming-Übergangs, abhängig von der Zellform der Nachbarschaft. Dies ist der bisher stärkste Beweis dafür, dass die Zellformen als Kontrollparameter für das 'Zelljamming' fungieren können. Die Zellanzahldichte beeinflusst ebenfalls das 'Jamming', ihr Einfluss kann jedoch als eine Verlangsamung der Eigengeschwindigkeit der Zellen beschrieben werden. Eine hohe Zellanzahldichte allein würde also nur die Viskosität des Gewebes erhöhen und es nicht verfestigen. Darüber hinaus habe ich gezeigt, dass es in dicht gepackten dreidimensionalen Zellsphäroiden sowie in Primärtumorstücken einen mit der Zellform verbundenen 'Jamming'-Übergang gibt. Ich verbinde das 'Unjamming' von Zellen mit dem Fortschreiten des Krebses, indem ich zeigte, dass die Herunterregulierung des Adhäsionsmoleküls E-Cadherin, die ein typischer Schritt während der Krebentwicklung ist, einen 'Unjamming'-Übergang verursacht. Bei diesem 'Unjamming'-Übergang kommt es zu einem ausgeprägten Verlust der Kohäsion und einem reduzierten Volumenanteil der Zellen, was zeigt, dass das 'Zelljamming' einen hohen Volumenanteil erfordert

Watersheds on edge or node weighted graphs

The literature on the watershed is separated in two families: the watersheds on node weighted graphs and the watersheds on edge weighted graphs. The simplest node weighted graphs are images, where the nodes are the pixels ; neighboring pixels being linked by unweighted pixels. The edge weights on an edge weighted graph express dissimilarities between the unweighted nodes. Distinct definitions of minima and catchment basins have been given for both types of graphs from which different algorithms have been derived. This paper aims at showing that watersheds on edge or node weighted graphs are strictly equivalent. Moreover, all algorithms developed for edge weighted graphs may be applied on node weighted graphs and vice versa. From any node or edge weighted graph it is possible to derive a flooding graph with node and edge weights. Its regional minima and catchment basins are identical whether one considers the node weights alone or the edge weights alone. A lexicographic order relation permits to compare non ascending paths with the same origin according to their steepness. Overlapping zones between neighboring catchment basins are reduced or even suppressed by pruning edges in the flooding graph through which does not pass a steepest path and reduces, without arbitrary choices the overlapping zones between adjacent catchment basins. We propose several ways to break the remaining ties, the simplest being to assign slightly distinct weights to regional minima with the same weight. Like that each node is linked with only one regional minimum by a path of maximal steepness

Active cellular mechanics and its consequences for animal development

A central goal of developmental biology is to understand how an organism shapes itself, a process referred to as morphogenesis. While the molecular components critical to determining the initial body plan have been well characterized, the control of the subsequent dynamics of cellular rearrangements which ultimately shape the organism are far less understood. A major roadblock to a more complete picture of morphogenesis is the inability to measure tissue-scale mechanics throughout development and thus answer fundamental questions: How is the mechanical state of the cell regulated by local protein expression and global pattering? In what way does stress feedback onto the larger developmental program?In this dissertation, we begin to approach these questions through the introduction and analysis of a multi-scale model of epithelial mechanics which explicitly connects cytoskeletal protein activity to tissue-level stress. In Chapter 2, we introduce the discrete Active Tension Network (ATN) model of cellular mechanics. ATNs are tissues that satisfy two primary assumptions: that the mechanical balance of cells is dominated by cortical tension and that myosin actively remodels the actin cytoskeleton in a stress-dependent manner. Remarkably, the interplay of these features allows for angle-preserving, i.e. `isogonal', dilations or contractions of local cell geometry that do not generate stress. Asymptotically this model is stabilized provided there is mechanical feedback on expression of myosin within the cell; we take this to be a strong prediction to be tested. The ATN model exposes a fundamental connection between equilibrium cell geometry and its underlying force network. In Chapter 3, we relax the tension-net approximation and demonstrate that at equilibrium, epithelial tissues with non-uniform pressure have non-trivial geometric constraints that imply the network is described by a weighted `dual' triangulation. We show that the dual triangulation encodes all information about the mechanical state of an epithelial tissue. Utilizing the stress-geometry ‘duality’, we formulate a local "Mechanical Inference" of cellular-level stress using solely cell geometry that dramatically improves over past image-based inference techniques.In Chapter 4, we generalize the ATN model to explore the controlled re-arrangement of cells within epithelial tissues. This requires us to explicitly consider the effects of cadherin mediated adhesion, and its regulation, on tissue morphogenesis. We find that positive feedback between myosin and cortical tension, along with traction-dependent depletion of cytoskeletal cadherin is sufficient to recapitulate the morphogenetic movement of cells observed during convergent extension of the lateral ectoderm during Drosophila embryogenesis. Statistical analyses of live-imaging data supports the fundamentals of the model.Chapter 5 focuses on morphogenesis at a mesoscopic scale by coarse-graining the cellular ATN model. Under this limit, we expect an epithelial tissue should behave as an effective viscous, compressible fluid driven by myosin gradients on intermediate time-scales. Theoretical predictions are empirically tested against in-toto microscopy data obtained during early Drosophila embryogenesis

Rheology and Collective Behavior in Living Tissue

Recent experiments and simulations have indicated that confluent epithelial layers, where there are no gaps or overlaps between the cells, can transition from a soft fluid-like state to a solid-like state, with dynamics that share many features with glass transitions. While a coherent picture has begun to form connecting the microscopic mechanisms that drive this transition with macroscopic observables, much less is known of its consequences in biological processes. Do tissues tune themselves to a fluid state in order to promote collective motion? Has evolution made use of the ability of tissues to tune themselves between fluid and solid states in programming the complex steps leading from the embryo to the organism? Here we describe our recent e↵orts to answer such questions using continuum and mesoscopic models. Employing the biophysical vertex model, active cells in confluent tissue are described as polygons with shape-based energies. Recent work has shown that this class of models yields a solid-liquid transition of tissue with evidence of glassy dynamics near the transition line. Here, we extend one such model to include the influence of cell division and cell death. With careful numerical studies, we refute a recent claim that the presence of such division and death will always fluidify the tissue. In the second part of the thesis, we develop a novel hydrodynamic model of confluent motile tissues that couples a structural order parameter for tissue rigidity to cell polarization. Using this continuum model we identify a new mechanism for pattern formation in confluent tissues via rigidity sensing that we name “morphotaxis”. We find that a single “morphotactic” parameter controls whether a tissue will remain homogeneous or will develop patterns such as asters and bands

Computer aided classification of histopathological damage in images of haematoxylin and eosin stained human skin

EngD ThesisExcised human skin can be used as a model to assess the potency, immunogenicity and contact sensitivity of potential therapeutics or cosmetics via the assessment of histological damage. The current method of assessing the damage uses traditional manual histological assessment, which is inherently subjective, time consuming and prone to intra-observer variability. Computer aided analysis has the potential to address issues surrounding traditional histological techniques through the application of quantitative analysis. This thesis describes the development of a computer aided process to assess the immune-mediated structural breakdown of human skin tissue. Research presented includes assessment and optimisation of image acquisition methodologies, development of an image processing and segmentation algorithm, identification and extraction of a novel set of descriptive image features and the evaluation of a selected subset of these features in a classification model. A new segmentation method is presented to identify epidermis tissue from skin with varying degrees of histopathological damage. Combining enhanced colour information with general image intensity information, the fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5% and segments effectively for different severities of tissue damage. A set of 140 feature measurements containing information about the tissue changes associated with different grades of histopathological skin damage were identified and a wrapper algorithm employed to select a subset of the extracted features, evaluating feature subsets based their prediction error for an independent test set in a Naïve Bayes Classifier. The final classification algorithm classified a 169 image set with an accuracy of 94.1%, of these images 20 were an unseen validation set for which the accuracy was 85.0%. The final classification method has a comparable accuracy to the existing manual method, improved repeatability and reproducibility and does not require an experienced histopathologist

On biophysical aspects of growth and dynamics of epithelial tissues

A fundamental and unresolved question of life is how organs are formed. The shape and form of organs emerges by spatio temporally controlled division and motility of cells. As both processes are tightly coordinated, interactions amongst cells are required to ensure stability and integrity. Many genetic networks controlling the polarised cell motility or promoting cell division have been identified. Action between cells results in an increased complexity. Yet cells give rise to regular patterned organs. The form of objects and their motion is subject to physical laws. Cells are of an active character, divide and move, interesting properties for a material, with potentially new knowledge emerging from their study. Here, we perform a quantitative characterisation of two experimental models for tissue morphogenesis. Using cultured epithelial sheets we address the mechanical properties of growth control and identify regulatory mechanisms. Based on this study, we propose a phenomenological description of tissue dynamics, reproducing the observed data. Using the methods developed to understand the cultured sheet, we approach the role of mechanics in the migration of an embryonic tissue. We measure the directed motion of the tissue and show that the findings can be reproduced by coupling the biophysical model of motile cells to a dynamically regulated polarisation mechanism.Formgebung von Organen ist ein grundlegendes, ungelöstes Problem des Lebens. Ihre Gestalt resultiert aus raumzeitlich kontrollierten Zellteilungen sowie Bewegungen von Zellen. Um mechanische Stabilität sowie Integrität des Gewebes zu gewährleisten, werden Zell-Zell Wechselwirkungen benötigt. Viele genetische Netzwerke kontrollieren die polarisierte Zellbeweglichkeit oder fördern die Zellteilung. Interaktion zwischen Zellen führt zu einer erhöhten Komplexität. Dennoch bilden sich reguläre Muster. Die Form von Objekten und deren Bewegung unterliegt physikalischen Gesetzen. Zellen sind von aktiver Art, teilen und bewegen sich, interessante Eigenschaften für ein Material, welche in neuen Erkenntnissen münden könnten. In dieser Arbeit führen wir eine quantitative Charakterisierung von zwei Modellsystemen der Morphogenese von Geweben durch. Anhand von kultivierten Epithelien behandeln wir die mechanischen Eigenschaften der Wachstumskontrolle und identifizieren Regulationsmechanismen. Darauf aufbauend, schlagen wir eine phänomenologische Modellbeschreibung für Gewebedynamik vor, welche die Beobachtungen reproduziert. Wir machen Gebrauch von diesen Methoden um die Mechanik der Migration eines embryonalen Epithels zu verstehen. Dabei messen wir die gerichtete Bewegung des Gewebes und zeigen, dass die resultierenden Daten durch Kopplung der biophysikalischen Motilitätsbeschreibung an einen dynamisch regulierten Polarisationsmechanismus reproduziert werden

Classifying the suras by their lexical semantics :an exploratory multivariate analysis approach to understanding the Qur'an

PhD ThesisThe Qur'an is at the heart of Islamic culture. Careful, well-informed interpretation of it is fundamental both to the faith of millions of Muslims throughout the world, and also to the non-Islamic world's understanding of their religion. There is a long and venerable tradition of Qur'anic interpretation, and it has necessarily been based on literary-historical methods for exegesis of hand-written and printed text. Developments in electronic text representation and analysis since the second half of the twentieth century now offer the opportunity to supplement traditional techniques by applying the newly-emergent computational technology of exploratory multivariate analysis to interpretation of the Qur'an. The general aim of the present discussion is to take up that opportunity. Specifically, the discussion develops and applies a methodology for discovering the thematic structure of the Qur'an based on a fundamental idea in a range of computationally oriented disciplines: that, with respect to some collection of texts, the lexical frequency profiles of the individual texts are a good indicator of their semantic content, and thus provide a reliable criterion for their conceptual categorization relative to one another. This idea is applied to the discovery of thematic interrelationships among the suras that constitute the Qur'an by abstracting lexical frequency data from them and then analyzing that data using exploratory multivariate methods in the hope that this will generate hypotheses about the thematic structure of the Qur'an. The discussion is in eight main parts. The first part introduces the discussion. The second gives an overview of the structure and thematic content of the Qur'an and of the tradition of Qur'anic scholarship devoted to its interpretation. The third part xvi defines the research question to be addressed together with a methodology for doing so. The fourth reviews the existing literature on the research question. The fifth outlines general principles of data creation and applies them to creation of the data on which the analysis of the Qur'an in this study is based. The sixth outlines general principles of exploratory multivariate analysis, describes in detail the analytical methods selected for use, and applies them to the data created in part five. The seventh part interprets the results of the analyses conducted in part six with reference to the existing results in Qur'anic interpretation described in part two. And, finally, the eighth part draws conclusions relative to the research question and identifies directions along which the work presented in this study can be developed

Template Based Recognition of On-Line Handwriting

Software for recognition of handwriting has been available for several decades now and research on the subject have produced several different strategies for producing competitive recognition accuracies, especially in the case of isolated single characters. The problem of recognizing samples of handwriting with arbitrary connections between constituent characters (emph{unconstrained handwriting}) adds considerable complexity in form of the segmentation problem. In other words a recognition system, not constrained to the isolated single character case, needs to be able to recognize where in the sample one letter ends and another begins. In the research community and probably also in commercial systems the most common technique for recognizing unconstrained handwriting compromise Neural Networks for partial character matching along with Hidden Markov Modeling for combining partial results to string hypothesis. Neural Networks are often favored by the research community since the recognition functions are more or less automatically inferred from a training set of handwritten samples. From a commercial perspective a downside to this property is the lack of control, since there is no explicit information on the types of samples that can be correctly recognized by the system. In a template based system, each style of writing a particular character is explicitly modeled, and thus provides some intuition regarding the types of errors (confusions) that the system is prone to make. Most template based recognition methods today only work for the isolated single character recognition problem and extensions to unconstrained recognition is usually not straightforward. This thesis presents a step-by-step recipe for producing a template based recognition system which extends naturally to unconstrained handwriting recognition through simple graph techniques. A system based on this construction has been implemented and tested for the difficult case of unconstrained online Arabic handwriting recognition with good results