TY - THES
AB - Chemokines organize immune cell trafficking by inducing either directed (tactic) or random (kinetic) migration and by activating integrins in order to support surface adhesion (haptic). Beyond that the same chemokines can establish clearly defined functional areas in secondary lymphoid organs. Until now it is unclear how chemokines can fulfill such diverse functions. One decisive prerequisite to explain these capacities is to know how chemokines are presented in tissue. In theory chemokines could occur either soluble or immobilized, and could be distributed either homogenously or as a concentration gradient. To dissect if and how the presenting mode of chemokines influences immune cells, I tested the response of dendritic cells (DCs) to differentially displayed chemokines. DCs are antigen presenting cells that reside in the periphery and migrate into draining lymph nodes (LNs) once exposed to inflammatory stimuli to activate naïve T cells. DCs are guided to and within the LN by the chemokine receptor CCR7, which has two ligands, the chemokines CCL19 and CCL21. Both CCR7 ligands are expressed by fibroblastic reticular cells in the LN, but differ in their ability to bind to heparan sulfate residues. CCL21 has a highly charged C-terminal extension, which mediates binding to anionic surfaces, whereas CCL19 is lacking such residues and likely distributes as a soluble molecule. This study shows that surface-bound CCL21 causes random, haptokinetic DC motility, which is confined to the chemokine coated area by insideout activation of β2 integrins that mediate cell binding to the surface. CCL19 on the other hand forms concentration gradients which trigger directional, chemotactic movement, but no surface adhesion. In addition DCs can actively manipulate this system by recruiting and activating serine proteases on their surfaces, which create - by proteolytically removing the adhesive C-terminus - a solubilized variant of CCL21 that functionally resembles CCL19. By generating a CCL21 concentration gradient DCs establish a positive feedback loop to recruit further DCs from the periphery to the CCL21 coated region. In addition DCs can sense chemotactic gradients as well as immobilized haptokinetic fields at the same time and integrate these signals. The result is chemotactically biased haptokinesis - directional migration confined to a chemokine coated track or area - which could explain the dynamic but spatially tightly controlled swarming leukocyte locomotion patterns that have been observed in lymphatic organs by intravital microscopists. The finding that DCs can approach soluble cues in a non-adhesive manner while they attach to surfaces coated with immobilized cues raises the question how these cells transmit intracellular forces to the environment, especially in the non-adherent migration mode. In order to migrate, cells have to generate and transmit force to the extracellular substrate. Force transmission is the prerequisite to procure an expansion of the leading edge and a forward motion of the whole cell body. In the current conceptions actin polymerization at the leading edge is coupled to extracellular ligands via the integrin family of transmembrane receptors, which allows the transmission of intracellular force. Against the paradigm of force transmission during migration, leukocytes, like DCs, are able to migrate in threedimensional environments without using integrin transmembrane receptors (Lämmermann et al., 2008). This reflects the biological function of leukocytes, as they can invade almost all tissues, whereby their migration has to be independent from the extracellular environment. How the cells can achieve this is unclear. For this study I examined DC migration in a defined threedimensional environment and highlighted actin-dynamics with the probe Lifeact-GFP. The result was that chemotactic DCs can switch between integrin-dependent and integrin- independent locomotion and can thereby adapt to the adhesive properties of their environment. If the cells are able to couple their actin cytoskeleton to the substrate, actin polymerization is entirely converted into protrusion. Without coupling the actin cortex undergoes slippage and retrograde actin flow can be observed. But retrograde actin flow can be completely compensated by higher actin polymerization rate keeping the migration velocity and the shape of the cells unaltered. Mesenchymal cells like fibroblast cannot balance the loss of adhesive interaction, cannot protrude into open space and, therefore, strictly depend on integrinmediated force coupling. This leukocyte specific phenomenon of “adaptive force transmission” endows these cells with the unique ability to transit and invade almost every type of tissue.
AU - Schumann, Kathrin
ID - 3275
TI - The role of chemotactic gradients in dendritic cell migration
ER -
TY - JOUR
AB - Diffusing membrane constituents are constantly exposed to a variety of forces that influence their stochastic path. Single molecule experiments allow for resolving trajectories at extremely high spatial and temporal accuracy, thereby offering insights into en route interactions of the tracer. In this review we discuss approaches to derive information about the underlying processes, based on single molecule tracking experiments. In particular, we focus on a new versatile way to analyze single molecule diffusion in the absence of a full analytical treatment. The method is based on comprehensive comparison of an experimental data set against the hypothetical outcome of multiple experiments performed on the computer. Since Monte Carlo simulations can be easily and rapidly performed even on state-of-the-art PCs, our method provides a simple way for testing various - even complicated - diffusion models. We describe the new method in detail, and show the applicability on two specific examples: firstly, kinetic rate constants can be derived for the transient interaction of mobile membrane proteins; secondly, residence time and corral size can be extracted for confined diffusion.
AU - Ruprecht, Verena
AU - Axmann, Markus
AU - Wieser, Stefan
AU - Schuetz, Gerhard
ID - 3287
IS - 8
JF - Current Protein & Peptide Science
TI - What can we learn from single molecule trajectories?
VL - 12
ER -
TY - JOUR
AB - The zonula adherens (ZA) of epithelial cells is a site of cell-cell adhesion where cellular forces are exerted and resisted. Increasing evidence indicates that E-cadherin adhesion molecules at the ZA serve to sense force applied on the junctions and coordinate cytoskeletal responses to those forces. Efforts to understand the role that cadherins play in mechanotransduction have been limited by the lack of assays to measure the impact of forces on the ZA. In this study we used 4D imaging of GFP-tagged E-cadherin to analyse the movement of the ZA. Junctions in confluent epithelial monolayers displayed prominent movements oriented orthogonal (perpendicular) to the ZA itself. Two components were identified in these movements: a relatively slow unidirectional (translational) component that could be readily fitted by least-squares regression analysis, upon which were superimposed more rapid oscillatory movements. Myosin IIB was a dominant factor responsible for driving the unilateral translational movements. In contrast, frequency spectrum analysis revealed that depletion of Myosin IIA increased the power of the oscillatory movements. This implies that Myosin IIA may serve to dampen oscillatory movements of the ZA. This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA.
AU - Smutny, Michael
AU - Wu, Selwin
AU - Gomez, Guillermo
AU - Mangold, Sabine
AU - Yap, Alpha
AU - Hamilton, Nicholas
ID - 3288
IS - 7
JF - PLoS One
TI - Multicomponent analysis of junctional movements regulated by Myosin II isoforms at the epithelial zonula adherens
VL - 6
ER -
TY - JOUR
AB - Analysis of genomic data requires an efficient way to calculate likelihoods across very large numbers of loci. We describe a general method for finding the distribution of genealogies: we allow migration between demes, splitting of demes [as in the isolation-with-migration (IM) model], and recombination between linked loci. These processes are described by a set of linear recursions for the generating function of branch lengths. Under the infinite-sites model, the probability of any configuration of mutations can be found by differentiating this generating function. Such calculations are feasible for small numbers of sampled genomes: as an example, we show how the generating function can be derived explicitly for three genes under the two-deme IM model. This derivation is done automatically, using Mathematica. Given data from a large number of unlinked and nonrecombining blocks of sequence, these results can be used to find maximum-likelihood estimates of model parameters by tabulating the probabilities of all relevant mutational configurations and then multiplying across loci. The feasibility of the method is demonstrated by applying it to simulated data and to a data set previously analyzed by Wang and Hey (2010) consisting of 26,141 loci sampled from Drosophila simulans and D. melanogaster. Our results suggest that such likelihood calculations are scalable to genomic data as long as the numbers of sampled individuals and mutations per sequence block are small.
AU - Lohse, Konrad
AU - Harrison, Richard
AU - Barton, Nicholas H
ID - 3290
IS - 3
JF - Genetics
TI - A general method for calculating likelihoods under the coalescent process
VL - 189
ER -
TY - CONF
AB - Animating detailed liquid surfaces has always been a challenge for computer graphics researchers and visual effects artists. Over the past few years, researchers in this field have focused on mesh-based surface tracking to synthesize extremely detailed liquid surfaces as efficiently as possible. This course provides a solid understanding of the steps required to create a fluid simulator with a mesh-based liquid surface.
The course begins with an overview of several existing liquid-surface-tracking techniques and the pros and cons of each method. Then it explains how to embed a triangle mesh into a finite-difference-based fluid simulator and describes several methods for allowing the liquid surface to merge together or break apart. The final section showcases the benefits and further applications of a mesh-based liquid surface, highlighting state-of-the-art methods for tracking colors and textures, maintaining liquid volume, preserving small surface features, and simulating realistic surface-tension waves.
AU - Wojtan, Christopher J
AU - Müller Fischer, Matthias
AU - Brochu, Tyson
ID - 3297
TI - Liquid simulation with mesh-based surface tracking
ER -
TY - CONF
AB - We present a new algorithm for enforcing incompressibility for Smoothed Particle Hydrodynamics (SPH) by preserving uniform density across the domain. We propose a hybrid method that uses a Poisson solve on a coarse grid to enforce a divergence free velocity ﬁeld, followed by a local density correction of the particles. This avoids typical grid artifacts and maintains the Lagrangian nature of SPH by directly transferring pressures onto particles. Our method can be easily integrated with existing SPH techniques such as the incompressible PCISPH method as well as weakly compressible SPH by adding an additional force term. We show that this hybrid method accelerates convergence towards uniform density and permits a signiﬁcantly larger time step compared to earlier approaches while producing similar results. We demonstrate our approach in a variety of scenarios with signiﬁcant pressure gradients such as splashing liquids.
AU - Raveendran, Karthik
AU - Wojtan, Christopher J
AU - Turk, Greg
ED - Spencer, Stephen
ID - 3298
TI - Hybrid smoothed particle hydrodynamics
ER -
TY - CONF
AB - We introduce propagation models, a formalism designed to support general and efficient data structures for the transient analysis of biochemical reaction networks. We give two use cases for propagation abstract data types: the uniformization method and numerical integration. We also sketch an implementation of a propagation abstract data type, which uses abstraction to approximate states.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 3299
TI - Propagation models for computing biochemical reaction networks
ER -
TY - CONF
AB - The chemical master equation is a differential equation describing the time evolution of the probability distribution over the possible “states” of a biochemical system. The solution of this equation is of interest within the systems biology field ever since the importance of the molec- ular noise has been acknowledged. Unfortunately, most of the systems do not have analytical solutions, and numerical solutions suffer from the course of dimensionality and therefore need to be approximated. Here, we introduce the concept of tail approximation, which retrieves an approximation of the probabilities in the tail of a distribution from the total probability of the tail and its conditional expectation. This approximation method can then be used to numerically compute the solution of the chemical master equation on a subset of the state space, thus fighting the explosion of the state space, for which this problem is renowned.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 3301
TI - Tail approximation for the chemical master equation
ER -
TY - CONF
AB - Cloud computing aims to give users virtually unlimited pay-per-use computing resources without the burden of managing the underlying infrastructure. We present a new job execution environment Flextic that exploits scal- able static scheduling techniques to provide the user with a flexible pricing model, such as a tradeoff between dif- ferent degrees of execution speed and execution price, and at the same time, reduce scheduling overhead for the cloud provider. We have evaluated a prototype of Flextic on Amazon EC2 and compared it against Hadoop. For various data parallel jobs from machine learning, im- age processing, and gene sequencing that we considered, Flextic has low scheduling overhead and reduces job du- ration by up to 15% compared to Hadoop, a dynamic cloud scheduler.
AU - Henzinger, Thomas A
AU - Singh, Anmol
AU - Singh, Vasu
AU - Wies, Thomas
AU - Zufferey, Damien
ID - 3302
TI - Static scheduling in clouds
ER -
TY - CHAP
AB - Alpha shapes have been conceived in 1981 as an attempt to define the shape of a finite set of point in the plane. Since then, connections to diverse areas in the sciences and engineering have developed, including to pattern recognition, digital shape sampling and processing, and structural molecular biology. This survey begins with a historical account and discusses geometric, algorithmic, topological, and combinatorial aspects of alpha shapes in this sequence.
AU - Herbert Edelsbrunner
ID - 3311
T2 - Tessellations in the Sciences
TI - Alpha shapes - a survey
ER -
TY - GEN
AB - We study the 3D reconstruction of plant roots from multiple 2D images. To meet the challenge caused by the delicate nature of thin branches, we make three innovations to cope with the sensitivity to image quality and calibration. First, we model the background as a harmonic function to improve the segmentation of the root in each 2D image. Second, we develop the concept of the regularized visual hull which reduces the effect of jittering and refraction by ensuring consistency with one 2D image. Third, we guarantee connectedness through adjustments to the 3D reconstruction that minimize global error. Our software is part of a biological phenotype/genotype study of agricultural root systems. It has been tested on more than 40 plant roots and results are promising in terms of reconstruction quality and efficiency.
AU - Zheng, Ying
AU - Gu, Steve
AU - Edelsbrunner, Herbert
AU - Tomasi, Carlo
AU - Benfey, Philip
ID - 3312
T2 - Proceedings of the IEEE International Conference on Computer Vision
TI - Detailed reconstruction of 3D plant root shape
ER -
TY - CONF
AB - Interpreting an image as a function on a compact sub- set of the Euclidean plane, we get its scale-space by diffu- sion, spreading the image over the entire plane. This gener- ates a 1-parameter family of functions alternatively defined as convolutions with a progressively wider Gaussian ker- nel. We prove that the corresponding 1-parameter family of persistence diagrams have norms that go rapidly to zero as time goes to infinity. This result rationalizes experimental observations about scale-space. We hope this will lead to targeted improvements of related computer vision methods.
AU - Chen, Chao
AU - Edelsbrunner, Herbert
ID - 3313
T2 - Proceedings of the IEEE International Conference on Computer Vision
TI - Diffusion runs low on persistence fast
ER -
TY - CONF
AB - We consider the offset-deconstruction problem: Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance µ in Hausdorff distance, as the Minkowski sum of another polygonal shape P with a disk of fixed radius? If it does, we also seek a preferably simple-looking solution shape P; then, P's offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give an O(n log n)-time exact decision algorithm that handles any polygonal shape, assuming the real-RAM model of computation. An alternative algorithm, based purely on rational arithmetic, answers the same deconstruction problem, up to an uncertainty parameter, and its running time depends on the parameter δ (in addition to the other input parameters: n, δ and the radius of the disk). If the input shape is found to be approximable, the rational-arithmetic algorithm also computes an approximate solution shape for the problem. For convex shapes, the complexity of the exact decision algorithm drops to O(n), which is also the time required to compute a solution shape P with at most one more vertex than a vertex-minimal one. Our study is motivated by applications from two different domains. However, since the offset operation has numerous uses, we anticipate that the reverse question that we study here will be still more broadly applicable. We present results obtained with our implementation of the rational-arithmetic algorithm.
AU - Berberich, Eric
AU - Halperin, Dan
AU - Kerber, Michael
AU - Pogalnikova, Roza
ID - 3329
T2 - Proceedings of the twenty-seventh annual symposium on Computational geometry
TI - Deconstructing approximate offsets
ER -
TY - CONF
AB - We consider the problem of approximating all real roots of a square-free polynomial f. Given isolating intervals, our algorithm refines each of them to a width at most 2-L, that is, each of the roots is approximated to L bits after the binary point. Our method provides a certified answer for arbitrary real polynomials, only requiring finite approximations of the polynomial coefficient and choosing a suitable working precision adaptively. In this way, we get a correct algorithm that is simple to implement and practically efficient. Our algorithm uses the quadratic interval refinement method; we adapt that method to be able to cope with inaccuracies when evaluating f, without sacrificing its quadratic convergence behavior. We prove a bound on the bit complexity of our algorithm in terms of degree, coefficient size and discriminant. Our bound improves previous work on integer polynomials by a factor of deg f and essentially matches best known theoretical bounds on root approximation which are obtained by very sophisticated algorithms.
AU - Kerber, Michael
AU - Sagraloff, Michael
ID - 3330
TI - Root refinement for real polynomials
ER -
TY - JOUR
AB - Given an algebraic hypersurface O in ℝd, how many simplices are necessary for a simplicial complex isotopic to O? We address this problem and the variant where all vertices of the complex must lie on O. We give asymptotically tight worst-case bounds for algebraic plane curves. Our results gradually improve known bounds in higher dimensions; however, the question for tight bounds remains unsolved for d ≥ 3.
AU - Kerber, Michael
AU - Sagraloff, Michael
ID - 3332
IS - 3
JF - Graphs and Combinatorics
TI - A note on the complexity of real algebraic hypersurfaces
VL - 27
ER -
TY - JOUR
AU - Edelsbrunner, Herbert
AU - Pach, János
AU - Ziegler, Günter
ID - 3334
IS - 1
JF - Discrete & Computational Geometry
TI - Letter from the new editors-in-chief
VL - 45
ER -
TY - CHAP
AB - We study the topology of the Megaparsec Cosmic Web in terms of the scale-dependent Betti numbers, which formalize the topological information content of the cosmic mass distribution. While the Betti numbers do not fully quantify topology, they extend the information beyond conventional cosmological studies of topology in terms of genus and Euler characteristic. The richer information content of Betti numbers goes along the availability of fast algorithms to compute them. For continuous density fields, we determine the scale-dependence of Betti numbers by invoking the cosmologically familiar filtration of sublevel or superlevel sets defined by density thresholds. For the discrete galaxy distribution, however, the analysis is based on the alpha shapes of the particles. These simplicial complexes constitute an ordered sequence of nested subsets of the Delaunay tessellation, a filtration defined by the scale parameter, α. As they are homotopy equivalent to the sublevel sets of the distance field, they are an excellent tool for assessing the topological structure of a discrete point distribution. In order to develop an intuitive understanding for the behavior of Betti numbers as a function of α, and their relation to the morphological patterns in the Cosmic Web, we first study them within the context of simple heuristic Voronoi clustering models. These can be tuned to consist of specific morphological elements of the Cosmic Web, i.e. clusters, filaments, or sheets. To elucidate the relative prominence of the various Betti numbers in different stages of morphological evolution, we introduce the concept of alpha tracks. Subsequently, we address the topology of structures emerging in the standard LCDM scenario and in cosmological scenarios with alternative dark energy content. The evolution of the Betti numbers is shown to reflect the hierarchical evolution of the Cosmic Web. We also demonstrate that the scale-dependence of the Betti numbers yields a promising measure of cosmological parameters, with a potential to help in determining the nature of dark energy and to probe primordial non-Gaussianities. We also discuss the expected Betti numbers as a function of the density threshold for superlevel sets of a Gaussian random field. Finally, we introduce the concept of persistent homology. It measures scale levels of the mass distribution and allows us to separate small from large scale features. Within the context of the hierarchical cosmic structure formation, persistence provides a natural formalism for a multiscale topology study of the Cosmic Web.
AU - Van De Weygaert, Rien
AU - Vegter, Gert
AU - Edelsbrunner, Herbert
AU - Jones, Bernard
AU - Pranav, Pratyush
AU - Park, Changbom
AU - Hellwing, Wojciech
AU - Eldering, Bob
AU - Kruithof, Nico
AU - Bos, Patrick
AU - Hidding, Johan
AU - Feldbrugge, Job
AU - Ten Have, Eline
AU - Van Engelen, Matti
AU - Caroli, Manuel
AU - Teillaud, Monique
ED - Gavrilova, Marina
ED - Tan, Kenneth
ED - Mostafavi, Mir
ID - 3335
T2 - Transactions on Computational Science XIV
TI - Alpha, Betti and the Megaparsec Universe: On the topology of the Cosmic Web
VL - 6970
ER -
TY - CONF
AB - In addition to being correct, a system should be robust, that is, it should behave reasonably even after receiving unexpected inputs. In this paper, we summarize two formal notions of robustness that we have introduced previously for reactive systems. One of the notions is based on assigning costs for failures on a user-provided notion of incorrect transitions in a specification. Here, we define a system to be robust if a finite number of incorrect inputs does not lead to an infinite number of incorrect outputs. We also give a more refined notion of robustness that aims to minimize the ratio of output failures to input failures. The second notion is aimed at liveness. In contrast to the previous notion, it has no concept of recovery from an error. Instead, it compares the ratio of the number of liveness constraints that the system violates to the number of liveness constraints that the environment violates.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
ID - 3316
T2 - 6th IEEE International Symposium on Industrial and Embedded Systems
TI - Specification-centered robustness
ER -
TY - JOUR
AB - Parvalbumin is thought to act in a manner similar to EGTA, but how a slow Ca2+ buffer affects nanodomain-coupling regimes at GABAergic synapses is unclear. Direct measurements of parvalbumin concentration and paired recordings in rodent hippocampus and cerebellum revealed that parvalbumin affects synaptic dynamics only when expressed at high levels. Modeling suggests that, in high concentrations, parvalbumin may exert BAPTA-like effects, modulating nanodomain coupling via competition with local saturation of endogenous fixed buffers.
AU - Eggermann, Emmanuel
AU - Jonas, Peter M
ID - 3318
JF - Nature Neuroscience
TI - How the “slow” Ca(2+) buffer parvalbumin affects transmitter release in nanodomain coupling regimes at GABAergic synapses
VL - 15
ER -
TY - CONF
AB - We address the problem of metric learning for multi-view data, namely the construction of embedding projections from data in different representations into a shared feature space, such that the Euclidean distance in this space provides a meaningful within-view as well as between-view similarity. Our motivation stems from the problem of cross-media retrieval tasks, where the availability of a joint Euclidean distance function is a pre-requisite to allow fast, in particular hashing-based, nearest neighbor queries. We formulate an objective function that expresses the intuitive concept that matching samples are mapped closely together in the output space, whereas non-matching samples are pushed apart, no matter in which view they are available. The resulting optimization problem is not convex, but it can be decomposed explicitly into a convex and a concave part, thereby allowing efficient optimization using the convex-concave procedure. Experiments on an image retrieval task show that nearest-neighbor based cross-view retrieval is indeed possible, and the proposed technique improves the retrieval accuracy over baseline techniques.
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 3319
TI - Learning multi-view neighborhood preserving projections
ER -